A new model for low-dose food challenge in children with allergy to milk or egg.

PubMed

Devenney, Irene; Norrman, Gunilla; Oldaeus, Göran; Strömberg, Leif; Fälth-Magnusson, Karin

2006-09-01

Atopic eczema and food allergy are common in early childhood. Children seem to gradually develop tolerance to milk and egg, and it is a relief for families when their child can tolerate small amounts of these basic foods, even if larger doses may still cause symptoms. To develop a model for low-dose oral food challenge, facilitating re-/introduction of milk or egg. In 39 children sensitized to milk and/or egg, we performed 52 challenges using a new standardized model for low-dose oral food challenge. The recipes were validated for blinding with sensorial tests. Four children challenged to milk had a positive challenge outcome. There were no significant differences with respect to family history, associated atopic manifestations, nutritional supply, eczema severity, or skin-prick test compared with the non-reacting children, but total and specific IgE values were significantly higher. All but two of the non-reacting children were able to introduce milk and egg into their diet without problems. We report recipes and a protocol to be used for standardized open and double-blind placebo-controlled low-dose food challenge in young children, enabling the introduction of small amounts of egg and milk into the diet during tolerance development.

Design of a framework for modeling, integration and simulation of physiological models.

PubMed

Erson, E Zeynep; Cavuşoğlu, M Cenk

2012-09-01

Multiscale modeling and integration of physiological models carry challenges due to the complex nature of physiological processes. High coupling within and among scales present a significant challenge in constructing and integrating multiscale physiological models. In order to deal with such challenges in a systematic way, there is a significant need for an information technology framework together with related analytical and computational tools that will facilitate integration of models and simulations of complex biological systems. Physiological Model Simulation, Integration and Modeling Framework (Phy-SIM) is an information technology framework providing the tools to facilitate development, integration and simulation of integrated models of human physiology. Phy-SIM brings software level solutions to the challenges raised by the complex nature of physiological systems. The aim of Phy-SIM, and this paper is to lay some foundation with the new approaches such as information flow and modular representation of the physiological models. The ultimate goal is to enhance the development of both the models and the integration approaches of multiscale physiological processes and thus this paper focuses on the design approaches that would achieve such a goal. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Challenges and opportunities for integrating lake ecosystem modelling approaches

USGS Publications Warehouse

Mooij, Wolf M.; Trolle, Dennis; Jeppesen, Erik; Arhonditsis, George; Belolipetsky, Pavel V.; Chitamwebwa, Deonatus B.R.; Degermendzhy, Andrey G.; DeAngelis, Donald L.; Domis, Lisette N. De Senerpont; Downing, Andrea S.; Elliott, J. Alex; Ruberto, Carlos Ruberto; Gaedke, Ursula; Genova, Svetlana N.; Gulati, Ramesh D.; Hakanson, Lars; Hamilton, David P.; Hipsey, Matthew R.; Hoen, Jochem 't; Hulsmann, Stephan; Los, F. Hans; Makler-Pick, Vardit; Petzoldt, Thomas; Prokopkin, Igor G.; Rinke, Karsten; Schep, Sebastiaan A.; Tominaga, Koji; Van Dam, Anne A.; Van Nes, Egbert H.; Wells, Scott A.; Janse, Jan H.

2010-01-01

A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others ('reinventing the wheel'). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available ('having tunnel vision'). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and trait-based models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its 'leading principle', there are many opportunities for combining approaches. We take the point of view that a single 'right' approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative view on the functioning of lake ecosystems. We end with a set of specific recommendations that may be of help in the further development of lake ecosystem models.

Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque’s and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines

PubMed Central

Kalkeri, Raj; Goebel, Scott; Cai, Zhaohui; Green, Brian; Lin, Shuling; Snyder, Beth; Hagelin, Kimberly; Walters, Kevin B.; Koide, Fusataka

2018-01-01

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose-dependent peak viral loads between days 2 and 5 post infection and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assay’s lower limit of quantitation, and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains, obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasure development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge. PMID:29723973

Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque's and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines.

PubMed

Rayner, Jonathan O; Kalkeri, Raj; Goebel, Scott; Cai, Zhaohui; Green, Brian; Lin, Shuling; Snyder, Beth; Hagelin, Kimberly; Walters, Kevin B; Koide, Fusataka

2018-05-01

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose-dependent peak viral loads between days 2 and 5 post infection and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assay’s lower limit of quantitation, and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains, obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasure development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

Exploring a Community of Practice Model for Professional Development to Address Challenges to Classroom Practices in Early Childhood

ERIC Educational Resources Information Center

Christ, Tanya; Wang, X. Christine

2013-01-01

This study explored whether or not, and how, an on-site and research-teacher community of practice model for professional development addressed the challenges to classroom practices in a Head Start program. Data sources included interviews with teachers, videos of planning and teaching sessions, and the researchers' fieldwork log and reflective…

"The Actualized Neurosurgeon": A Proposed Model of Surgical Resident Development.

PubMed

Lipsman, Nir; Khan, Osaama; Kulkarni, Abhaya V

2017-03-01

Modern neurosurgical training is both physically and emotionally demanding, posing significant challenges, new and old, to residents as well as programs attempting to train safe, competent surgeons. Models to describe resident development, such as the Accreditation Council for Graduate Medical Education competencies and milestones, address the acquisition of specific skills but largely ignore the stresses and pressures unique to each stage of resident training. We propose an alternative model of resident development adapted from the developmental psychology literature. Our model identifies the challenges that must be met at each stage of junior, intermediate, and senior and chief residency, leading ultimately to an "actualized" neurosurgeon (i.e., one who has maximized his or her potential). Failure to overcome any 1 of these challenges can lead to specific long-lasting consequences, including regret, identity crisis, incompetence, and bitterness. In contrast, the actualized surgeon is one who has successfully acquired the virtues of hope, will, purpose, fidelity, productivity, leadership, competence, and wisdom. The actualized surgeon not only functions safely, confidently, and professionally, but also successfully navigates the challenges of residency and emerges from them having fulfilled his or her maximal potential. This developmental perspective provides an individualized description of healthy surgical development. Our model allows programs to identify the basis for residents who fail to progress, counsel residents during their training, and perhaps help identify resident candidates who are better prepared to meet the developmental challenges of residency training. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of a design challenge to develop postural support devices for intermediate wheelchair users

PubMed Central

Tanuku, Deepti; Moller, Nathaniel C.

2017-01-01

The provision of an appropriate wheelchair, one that provides proper fit and postural support, promotes wheelchair users’ physical health and quality of life. Many wheelchair users have postural difficulties, requiring supplemental postural support devices for added trunk support. However, in many low- and middle-income settings, postural support devices are inaccessible, inappropriate or unaffordable. This article describes the use of the design challenge model, informed by a design thinking approach, to catalyse the development of an affordable, simple and robust postural support device for low- and middle-income countries. The article also illustrates how not-for-profit organisations can utilise design thinking and, in particular, the design challenge model to successfully support the development of innovative solutions to product or process challenges. PMID:28936418

NEW DIRECTIONS AND CHALLENGES FOR THE COMMUNITY EARTH SYSTEM MODELIn this talk, we will discuss the upcoming release of CESM2 and the challenges encountered in the process. We will then discuss upcoming new opportunities in development and applications of Earth System Models

NASA Astrophysics Data System (ADS)

Lamarque, J. F.

2016-12-01

In this talk, we will discuss the upcoming release of CESM2 and the computational and scientific challenges encountered in the process. We will then discuss upcoming new opportunities in development and applications of Earth System Models; in particular, we will discuss additional ways in which the university community can contribute to CESM.

Validation of the thermal challenge problem using Bayesian Belief Networks.

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

McFarland, John; Swiler, Laura Painton

The thermal challenge problem has been developed at Sandia National Laboratories as a testbed for demonstrating various types of validation approaches and prediction methods. This report discusses one particular methodology to assess the validity of a computational model given experimental data. This methodology is based on Bayesian Belief Networks (BBNs) and can incorporate uncertainty in experimental measurements, in physical quantities, and model uncertainties. The approach uses the prior and posterior distributions of model output to compute a validation metric based on Bayesian hypothesis testing (a Bayes' factor). This report discusses various aspects of the BBN, specifically in the context ofmore » the thermal challenge problem. A BBN is developed for a given set of experimental data in a particular experimental configuration. The development of the BBN and the method for ''solving'' the BBN to develop the posterior distribution of model output through Monte Carlo Markov Chain sampling is discussed in detail. The use of the BBN to compute a Bayes' factor is demonstrated.« less

Development of a waterborne challenge model for Flavobacterium psychrophilum.

PubMed

Long, Amy; Fehringer, Tyson R; LaFrentz, Benjamin R; Call, Douglas R; Cain, Kenneth D

2014-10-01

Flavobacterium psychrophilum is the causative agent of bacterial coldwater disease and can cause significant mortality in salmonid aquaculture. To better evaluate disease prevention or treatment methods for F. psychrophilum in the laboratory, a waterborne challenge model that mimics a natural outbreak is needed. Here we report on the development of a waterborne challenge model for F. psychrophilum in which we incorporated variables that may influence challenge success: specifically, scarification prior to bacterial exposure and culture of F. psychrophilum under iron-limited culture conditions to potentially increase the probability of establishing disease. Additionally, two F. psychrophilum strains, CSF 259-93 and THC 02-90, were used in this model to test whether there were virulence differences between strains. Mortality was significantly higher in scarred fish than unscarred fish (81.5 vs. 19.4%), supporting the hypothesis that disruptions in the dermal layer enhance mortality in F. psychrophilum waterborne challenges. Although mortality differences were not significant between iron-replete and iron-limited treatments, mortality was high overall (> 30%). There was a significant difference in mortality between CSF 259-93 and THC 02-90 treatments, although both strains caused high mortality in injection challenges. In conclusion, this waterborne challenge model can be used to evaluate potential disease prevention and treatment methods. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Modeling sustainability in renewable energy supply chain systems

NASA Astrophysics Data System (ADS)

Xie, Fei

This dissertation aims at modeling sustainability of renewable fuel supply chain systems against emerging challenges. In particular, the dissertation focuses on the biofuel supply chain system design, and manages to develop advanced modeling framework and corresponding solution methods in tackling challenges in sustaining biofuel supply chain systems. These challenges include: (1) to integrate "environmental thinking" into the long-term biofuel supply chain planning; (2) to adopt multimodal transportation to mitigate seasonality in biofuel supply chain operations; (3) to provide strategies in hedging against uncertainty from conversion technology; and (4) to develop methodologies in long-term sequential planning of the biofuel supply chain under uncertainties. All models are mixed integer programs, which also involves multi-objective programming method and two-stage/multistage stochastic programming methods. In particular for the long-term sequential planning under uncertainties, to reduce the computational challenges due to the exponential expansion of the scenario tree, I also developed efficient ND-Max method which is more efficient than CPLEX and Nested Decomposition method. Through result analysis of four independent studies, it is found that the proposed modeling frameworks can effectively improve the economic performance, enhance environmental benefits and reduce risks due to systems uncertainties for the biofuel supply chain systems.

Seven challenges for metapopulation models of epidemics, including households models.

PubMed

Ball, Frank; Britton, Tom; House, Thomas; Isham, Valerie; Mollison, Denis; Pellis, Lorenzo; Scalia Tomba, Gianpaolo

2015-03-01

This paper considers metapopulation models in the general sense, i.e. where the population is partitioned into sub-populations (groups, patches,...), irrespective of the biological interpretation they have, e.g. spatially segregated large sub-populations, small households or hosts themselves modelled as populations of pathogens. This framework has traditionally provided an attractive approach to incorporating more realistic contact structure into epidemic models, since it often preserves analytic tractability (in stochastic as well as deterministic models) but also captures the most salient structural inhomogeneity in contact patterns in many applied contexts. Despite the progress that has been made in both the theory and application of such metapopulation models, we present here several major challenges that remain for future work, focusing on models that, in contrast to agent-based ones, are amenable to mathematical analysis. The challenges range from clarifying the usefulness of systems of weakly-coupled large sub-populations in modelling the spread of specific diseases to developing a theory for endemic models with household structure. They include also developing inferential methods for data on the emerging phase of epidemics, extending metapopulation models to more complex forms of human social structure, developing metapopulation models to reflect spatial population structure, developing computationally efficient methods for calculating key epidemiological model quantities, and integrating within- and between-host dynamics in models. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

DEVELOPMENT OF CFD SIMULATION APPLICATIONS FOR LOCAL-SCALE AREAS AND POTENTIAL INTERFACE WITH MESOSCALE MODELS

EPA Science Inventory

The presentation summarizes developments of ongoing applications of fine-scale (geometry specific) CFD simulations to urban areas within atmospheric boundary layers. Enabling technology today and challenges for the future are discussed. There is a challenging need to develop a ...

78 FR 70303 - Announcement of Requirements and Registration for the Predict the Influenza Season Challenge

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-25

... public. Mathematical and statistical models can be useful in predicting the timing and impact of the... applying any mathematical, statistical, or other approach to predictive modeling. This challenge will... Services (HHS) region level(s) in the United States by developing mathematical and statistical models that...

A Modeling Approach to the Development of Students' Informal Inferential Reasoning

ERIC Educational Resources Information Center

Doerr, Helen M.; Delmas, Robert; Makar, Katie

2017-01-01

Teaching from an informal statistical inference perspective can address the challenge of teaching statistics in a coherent way. We argue that activities that promote model-based reasoning address two additional challenges: providing a coherent sequence of topics and promoting the application of knowledge to novel situations. We take a models and…

Development of a waterborne challenge model for Flavobacterium psychrophilum

USDA-ARS?s Scientific Manuscript database

Flavobacterium psychrophilum is the causative agent of bacterial coldwater disease and can cause significant mortality in salmonid aquaculture. To better evaluate disease prevention or treatment methods for F. psychrophilum in the laboratory, a waterborne challenge model that mimics a natural outbre...

Core Competencies for Doctoral Education in Public Health

PubMed Central

Calhoun, Judith G.; Weist, Elizabeth M.; Raczynski, James M.

2012-01-01

The Association of Schools of Public Health (ASPH) released the Doctor of Public Health (DrPH) Core Competency Model in 2009. Between 2007 and 2009, a national expert panel with members of the academic and practice communities guided by the ASPH Education Committee developed its 7 performance domains, including 54 competencies. We provide an overview and analysis of the challenges and issues associated with the variability in DrPH degree offerings, reflect on the model development process and related outcomes, and discuss the significance of the model, future applications, and challenges for integration across educational settings. With the model, ASPH aims to stimulate national discussion on the competencies needed by DrPH graduates with the new challenges of 21st-century public health practice and to better define the DrPH degree. PMID:22095342

Addressing current challenges in cancer immunotherapy with mathematical and computational modelling.

PubMed

Konstorum, Anna; Vella, Anthony T; Adler, Adam J; Laubenbacher, Reinhard C

2017-06-01

The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour-immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development. © 2017 The Author(s).

Assessing cost-effectiveness of HPV vaccines with decision analytic models: what are the distinct challenges of low- and middle-income countries? A protocol for a systematic review.

PubMed

Ekwunife, Obinna I; Grote, Andreas Gerber; Mosch, Christoph; O'Mahony, James F; Lhachimi, Stefan K

2015-05-12

Cervical cancer poses a huge health burden, both to developed and developing nations, making prevention and control strategies necessary. However, the challenges of designing and implementing prevention strategies differ for low- and middle-income countries (LMICs) as compared to countries with fully developed health care systems. Moreover, for many LMICs, much of the data needed for decision analytic modelling, such as prevalence, will most likely only be partly available or measured with much larger uncertainty. Lastly, imperfect implementation of human papillomavirus (HPV) vaccination may influence the effectiveness of cervical cancer prevention in unpredictable ways. This systematic review aims to assess how decision analytic modelling studies of HPV cost-effectiveness in LMICs accounted for the particular challenges faced in such countries. Specifically, the study will assess the following: (1) whether the existing literature on cost-effectiveness modelling of HPV vaccines acknowledges the distinct challenges of LMICs, (2) how these challenges were accommodated in the models, (3) whether certain parameters systemically exhibited large degrees of uncertainty due to lack of data and how influential were these parameters on model-based recommendations, and (4) whether the choice of modelling herd immunity influences model-based recommendations, especially when coverage of a HPV vaccination program is not optimal. We will conduct a systematic review to identify suitable studies from MEDLINE (via PubMed), EMBASE, NHS Economic Evaluation Database (NHS EED), EconLit, Web of Science, and CEA Registry. Searches will be conducted for studies of interest published since 2006. The searches will be supplemented by hand searching of the most relevant papers found in the search. Studies will be critically appraised using Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement checklist. We will undertake a descriptive, narrative, and interpretative synthesis of data to address the study objectives. The proposed systematic review will assess how the cost-effectiveness studies of HPV vaccines accounted for the distinct challenges of LMICs. The gaps identified will expose areas for additional research as well as challenges that need to be accounted for in future modelling studies. PROSPERO CRD42015017870.

Genetic Simulation Tools for Post-Genome Wide Association Studies of Complex Diseases

PubMed Central

Amos, Christopher I.; Bafna, Vineet; Hauser, Elizabeth R.; Hernandez, Ryan D.; Li, Chun; Liberles, David A.; McAllister, Kimberly; Moore, Jason H.; Paltoo, Dina N.; Papanicolaou, George J.; Peng, Bo; Ritchie, Marylyn D.; Rosenfeld, Gabriel; Witte, John S.

2014-01-01

Genetic simulation programs are used to model data under specified assumptions to facilitate the understanding and study of complex genetic systems. Standardized data sets generated using genetic simulation are essential for the development and application of novel analytical tools in genetic epidemiology studies. With continuing advances in high-throughput genomic technologies and generation and analysis of larger, more complex data sets, there is a need for updating current approaches in genetic simulation modeling. To provide a forum to address current and emerging challenges in this area, the National Cancer Institute (NCI) sponsored a workshop, entitled “Genetic Simulation Tools for Post-Genome Wide Association Studies of Complex Diseases” at the National Institutes of Health (NIH) in Bethesda, Maryland on March 11-12, 2014. The goals of the workshop were to: (i) identify opportunities, challenges and resource needs for the development and application of genetic simulation models; (ii) improve the integration of tools for modeling and analysis of simulated data; and (iii) foster collaborations to facilitate development and applications of genetic simulation. During the course of the meeting the group identified challenges and opportunities for the science of simulation, software and methods development, and collaboration. This paper summarizes key discussions at the meeting, and highlights important challenges and opportunities to advance the field of genetic simulation. PMID:25371374

Challenges to Apprenticeship Learning in Religious Education: Narrow Use of the Apprenticeship Model and Current Developments in Youth Ministry

ERIC Educational Resources Information Center

de Kock, A.

2017-01-01

In 2012, I proposed the apprenticeship model as a promising catechetical model for church communities in which catechists might be hope generators, and the church community becomes a community of hope. This article argues that the original meaning of the apprenticeship model is challenged by an emphasis in youth ministry practices on the…

A systematic review and checklist presenting the main challenges for health economic modeling in personalized medicine: towards implementing patient-level models.

PubMed

Degeling, Koen; Koffijberg, Hendrik; IJzerman, Maarten J

2017-02-01

The ongoing development of genomic medicine and the use of molecular and imaging markers in personalized medicine (PM) has arguably challenged the field of health economic modeling (HEM). This study aims to provide detailed insights into the current status of HEM in PM, in order to identify if and how modeling methods are used to address the challenges described in literature. Areas covered: A review was performed on studies that simulate health economic outcomes for personalized clinical pathways. Decision tree modeling and Markov modeling were the most observed methods. Not all identified challenges were frequently found, challenges regarding companion diagnostics, diagnostic performance, and evidence gaps were most often found. However, the extent to which challenges were addressed varied considerably between studies. Expert commentary: Challenges for HEM in PM are not yet routinely addressed which may indicate that either (1) their impact is less severe than expected, (2) they are hard to address and therefore not managed appropriately, or (3) HEM in PM is still in an early stage. As evidence on the impact of these challenges is still lacking, we believe that more concrete examples are needed to illustrate the identified challenges and to demonstrate methods to handle them.

Challenges in Japanese Teachers' Professional Development: A Focus on an Alternative Perspective

ERIC Educational Resources Information Center

Arani, Mohammad Reza Sarkar; Matoba, Masami

2006-01-01

In this paper we examine challenges of Japanese teachers' professional development which points to the essential change in in-service teacher training programs. Emphasis is placed here on an integrated model for professional development that should be deliberately designed to assist teacher training to construct an understanding of the spirit of…

Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities

PubMed Central

Bardhan, Jaydeep P.

2014-01-01

In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g. molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding features such as nonlocal dielectric response, and nonlinearities resulting from dielectric saturation. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost forty years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The paper concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics. PMID:25505358

Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities.

PubMed

Bardhan, Jaydeep P

2013-12-01

In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g. molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding features such as nonlocal dielectric response, and nonlinearities resulting from dielectric saturation. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost forty years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The paper concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.

Gradient models in molecular biophysics: progress, challenges, opportunities

NASA Astrophysics Data System (ADS)

Bardhan, Jaydeep P.

2013-12-01

In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g., molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding nonlocal dielectric response. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain, and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost 40 years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The review concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.

Scaling Equations for Ballistic Modeling of Solid Rocket Motor Case Breach

NASA Technical Reports Server (NTRS)

McMillin, Joshua E.

2006-01-01

This paper explores the development of a series of scaling equations that can take a known nominal motor performance and scale it for small and growing case failures. This model was developed for the Malfunction-Turn Study as part of Return to Flight activities for the Space Shuttle program. To verify the model, data from the Challenger accident (STS- 51L) were used. The model is able to predict the motor performance beyond the last recorded Challenger data and show how the failed right hand booster would have performed if the vehicle had remained intact.

An integrated conceptual framework for evaluating and improving 'understanding' in informed consent.

PubMed

Bossert, Sabine; Strech, Daniel

2017-10-17

The development of understandable informed consent (IC) documents has proven to be one of the most important challenges in research with humans as well as in healthcare settings. Therefore, evaluating and improving understanding has been of increasing interest for empirical research on IC. However, several conceptual and practical challenges for the development of understandable IC documents remain unresolved. In this paper, we will outline and systematize some of these challenges. On the basis of our own experiences in empirical user testing of IC documents as well as the relevant literature on understanding in IC, we propose an integrated conceptual model for the development of understandable IC documents. The proposed conceptual model integrates different methods for the participatory improvement of written information, including IC, as well as quantitative methods for measuring understanding in IC. In most IC processes, understandable written information is an important prerequisite for valid IC. To improve the quality of IC documents, a conceptual model for participatory procedures of testing, revising, and retesting can be applied. However, the model presented in this paper needs further theoretical and empirical elaboration and clarification of several conceptual and practical challenges.

COMPUTATIONAL CHALLENGES IN BUILDING MULTI-SCALE AND MULTI-PHYSICS MODELS OF CARDIAC ELECTRO-MECHANICS

PubMed Central

Plank, G; Prassl, AJ; Augustin, C

2014-01-01

Despite the evident multiphysics nature of the heart – it is an electrically controlled mechanical pump – most modeling studies considered electrophysiology and mechanics in isolation. In no small part, this is due to the formidable modeling challenges involved in building strongly coupled anatomically accurate and biophyically detailed multi-scale multi-physics models of cardiac electro-mechanics. Among the main challenges are the selection of model components and their adjustments to achieve integration into a consistent organ-scale model, dealing with technical difficulties such as the exchange of data between electro-physiological and mechanical model, particularly when using different spatio-temporal grids for discretization, and, finally, the implementation of advanced numerical techniques to deal with the substantial computational. In this study we report on progress made in developing a novel modeling framework suited to tackle these challenges. PMID:24043050

Building confidence and credibility amid growing model and computing complexity

NASA Astrophysics Data System (ADS)

Evans, K. J.; Mahajan, S.; Veneziani, C.; Kennedy, J. H.

2017-12-01

As global Earth system models are developed to answer an ever-wider range of science questions, software products that provide robust verification, validation, and evaluation must evolve in tandem. Measuring the degree to which these new models capture past behavior, predict the future, and provide the certainty of predictions is becoming ever more challenging for reasons that are generally well known, yet are still challenging to address. Two specific and divergent needs for analysis of the Accelerated Climate Model for Energy (ACME) model - but with a similar software philosophy - are presented to show how a model developer-based focus can address analysis needs during expansive model changes to provide greater fidelity and execute on multi-petascale computing facilities. A-PRIME is a python script-based quick-look overview of a fully-coupled global model configuration to determine quickly if it captures specific behavior before significant computer time and expense is invested. EVE is an ensemble-based software framework that focuses on verification of performance-based ACME model development, such as compiler or machine settings, to determine the equivalence of relevant climate statistics. The challenges and solutions for analysis of multi-petabyte output data are highlighted from the aspect of the scientist using the software, with the aim of fostering discussion and further input from the community about improving developer confidence and community credibility.

Numerical simulation of turbulent combustion: Scientific challenges

NASA Astrophysics Data System (ADS)

Ren, ZhuYin; Lu, Zhen; Hou, LingYun; Lu, LiuYan

2014-08-01

Predictive simulation of engine combustion is key to understanding the underlying complicated physicochemical processes, improving engine performance, and reducing pollutant emissions. Critical issues as turbulence modeling, turbulence-chemistry interaction, and accommodation of detailed chemical kinetics in complex flows remain challenging and essential for high-fidelity combustion simulation. This paper reviews the current status of the state-of-the-art large eddy simulation (LES)/prob-ability density function (PDF)/detailed chemistry approach that can address the three challenging modelling issues. PDF as a subgrid model for LES is formulated and the hybrid mesh-particle method for LES/PDF simulations is described. Then the development need in micro-mixing models for the PDF simulations of turbulent premixed combustion is identified. Finally the different acceleration methods for detailed chemistry are reviewed and a combined strategy is proposed for further development.

Key challenges and priorities for modelling European grasslands under climate change.

PubMed

Kipling, Richard P; Virkajärvi, Perttu; Breitsameter, Laura; Curnel, Yannick; De Swaef, Tom; Gustavsson, Anne-Maj; Hennart, Sylvain; Höglind, Mats; Järvenranta, Kirsi; Minet, Julien; Nendel, Claas; Persson, Tomas; Picon-Cochard, Catherine; Rolinski, Susanne; Sandars, Daniel L; Scollan, Nigel D; Sebek, Leon; Seddaiu, Giovanna; Topp, Cairistiona F E; Twardy, Stanislaw; Van Middelkoop, Jantine; Wu, Lianhai; Bellocchi, Gianni

2016-10-01

Grassland-based ruminant production systems are integral to sustainable food production in Europe, converting plant materials indigestible to humans into nutritious food, while providing a range of environmental and cultural benefits. Climate change poses significant challenges for such systems, their productivity and the wider benefits they supply. In this context, grassland models have an important role in predicting and understanding the impacts of climate change on grassland systems, and assessing the efficacy of potential adaptation and mitigation strategies. In order to identify the key challenges for European grassland modelling under climate change, modellers and researchers from across Europe were consulted via workshop and questionnaire. Participants identified fifteen challenges and considered the current state of modelling and priorities for future research in relation to each. A review of literature was undertaken to corroborate and enrich the information provided during the horizon scanning activities. Challenges were in four categories relating to: 1) the direct and indirect effects of climate change on the sward 2) climate change effects on grassland systems outputs 3) mediation of climate change impacts by site, system and management and 4) cross-cutting methodological issues. While research priorities differed between challenges, an underlying theme was the need for accessible, shared inventories of models, approaches and data, as a resource for stakeholders and to stimulate new research. Developing grassland models to effectively support efforts to tackle climate change impacts, while increasing productivity and enhancing ecosystem services, will require engagement with stakeholders and policy-makers, as well as modellers and experimental researchers across many disciplines. The challenges and priorities identified are intended to be a resource 1) for grassland modellers and experimental researchers, to stimulate the development of new research directions and collaborative opportunities, and 2) for policy-makers involved in shaping the research agenda for European grassland modelling under climate change. Copyright © 2016 Elsevier B.V. All rights reserved.

Environmental Flow Modeling Challenges for Rapidly Urbanizing Watersheds

EPA Science Inventory

It is a challenge for land use planners and water resource managers to balance water needs that support urban growth and economic development of a growing population and yet maintain ecological flow needs. Urban growth and the associated water resources development in a watershed...

Rocks in the River: The Challenge of Piloting the Inquiry Process in Today's Learning Environment

ERIC Educational Resources Information Center

Lambusta, Patrice; Graham, Sandy; Letteri-Walker, Barbara

2014-01-01

School librarians in Newport News, Virginia, are meeting the challenges of integrating an Inquiry Process Model into instruction. In the original model the process began by asking students to develop questions to start their inquiry journey. As this model was taught it was discovered that students often did not have enough background knowledge to…

Organoids as Models for Neoplastic Transformation | Office of Cancer Genomics

Cancer.gov

Cancer models strive to recapitulate the incredible diversity inherent in human tumors. A key challenge in accurate tumor modeling lies in capturing the panoply of homo- and heterotypic cellular interactions within the context of a three-dimensional tissue microenvironment. To address this challenge, researchers have developed organotypic cancer models (organoids) that combine the 3D architecture of in vivo tissues with the experimental facility of 2D cell lines.

Interrogating HIV integrase for compounds that bind- a SAMPL challenge

NASA Astrophysics Data System (ADS)

Peat, Thomas S.; Dolezal, Olan; Newman, Janet; Mobley, David; Deadman, John J.

2014-04-01

Tremendous gains and novel methods are often developed when people are challenged to do something new or difficult. This process is enhanced when people compete against each other-this can be seen in sport as well as in science and technology (e.g. the space race). The SAMPL challenges, like the CASP challenges, aim to challenge modellers and software developers to develop new ways of looking at molecular interactions so the community as a whole can progress in the accurate prediction of these interactions. In order for this challenge to occur, data must be supplied so the prospective test can be done. We have supplied unpublished data related to a drug discovery program run several years ago on HIV integrase for the SAMPL4 challenge. This paper describes the methods used to obtain these data and the chemistry involved.

Dual-Mode Teacher Professional Development: Challenges and Re-Visioning Future TPD in Indonesia

ERIC Educational Resources Information Center

Widodo, Ari; Riandi

2013-01-01

This paper presents the results of a two-year research project aimed at developing a teacher professional development (TPD) model in Indonesia. New government policies in this nation, its archipelagic nature, vast numbers of teachers and scarcity of support resources present a unique challenge to TPD. A needs assessment was conducted to identify…

Keep it simple - A case study of model development in the context of the Dynamic Stocks and Flows (DSF) task

NASA Astrophysics Data System (ADS)

Halbrügge, Marc

2010-12-01

This paper describes the creation of a cognitive model submitted to the ‘Dynamic Stocks and Flows’ (DSF) modeling challenge. This challenge aims at comparing computational cognitive models for human behavior during an open ended control task. Participants in the modeling competition were provided with a simulation environment and training data for benchmarking their models while the actual specification of the competition task was withheld. To meet this challenge, the cognitive model described here was designed and optimized for generalizability. Only two simple assumptions about human problem solving were used to explain the empirical findings of the training data. In-depth analysis of the data set prior to the development of the model led to the dismissal of correlations or other parametric statistics as goodness-of-fit indicators. A new statistical measurement based on rank orders and sequence matching techniques is being proposed instead. This measurement, when being applied to the human sample, also identifies clusters of subjects that use different strategies for the task. The acceptability of the fits achieved by the model is verified using permutation tests.

The Future of Electronic Device Design: Device and Process Simulation Find Intelligence on the World Wide Web

NASA Technical Reports Server (NTRS)

Biegel, Bryan A.

1999-01-01

We are on the path to meet the major challenges ahead for TCAD (technology computer aided design). The emerging computational grid will ultimately solve the challenge of limited computational power. The Modular TCAD Framework will solve the TCAD software challenge once TCAD software developers realize that there is no other way to meet industry's needs. The modular TCAD framework (MTF) also provides the ideal platform for solving the TCAD model challenge by rapid implementation of models in a partial differential solver.

Challenges in the development of very high resolution Earth System Models for climate science

NASA Astrophysics Data System (ADS)

Rasch, Philip J.; Xie, Shaocheng; Ma, Po-Lun; Lin, Wuyin; Wan, Hui; Qian, Yun

2017-04-01

The authors represent the 20+ members of the ACME atmosphere development team. The US Department of Energy (DOE) has, like many other organizations around the world, identified the need for an Earth System Model capable of rapid completion of decade to century length simulations at very high (vertical and horizontal) resolution with good climate fidelity. Two years ago DOE initiated a multi-institution effort called ACME (Accelerated Climate Modeling for Energy) to meet this an extraordinary challenge, targeting a model eventually capable of running at 10-25km horizontal and 20-400m vertical resolution through the troposphere on exascale computational platforms at speeds sufficient to complete 5+ simulated years per day. I will outline the challenges our team has encountered in development of the atmosphere component of this model, and the strategies we have been using for tuning and debugging a model that we can barely afford to run on today's computational platforms. These strategies include: 1) evaluation at lower resolutions; 2) ensembles of short simulations to explore parameter space, and perform rough tuning and evaluation; 3) use of regionally refined versions of the model for probing high resolution model behavior at less expense; 4) use of "auto-tuning" methodologies for model tuning; and 5) brute force long climate simulations.

The space shuttle ascent vehicle aerodynamic challenges configuration design and data base development

NASA Technical Reports Server (NTRS)

Dill, C. C.; Young, J. C.; Roberts, B. B.; Craig, M. K.; Hamilton, J. T.; Boyle, W. W.

1985-01-01

The phase B Space Shuttle systems definition studies resulted in a generic configuration consisting of a delta wing orbiter, and two solid rocket boosters (SRB) attached to an external fuel tank (ET). The initial challenge facing the aerodynamic community was aerodynamically optimizing, within limits, this configuration. As the Shuttle program developed and the sensitivities of the vehicle to aerodynamics were better understood the requirements of the aerodynamic data base grew. Adequately characterizing the vehicle to support the various design studies exploded the size of the data base to proportions that created a data modeling/management challenge for the aerodynamicist. The ascent aerodynamic data base originated primarily from wind tunnel test results. The complexity of the configuration rendered conventional analytic methods of little use. Initial wind tunnel tests provided results which included undesirable effects from model support tructure, inadequate element proximity, and inadequate plume simulation. The challenge to improve the quality of test results by determining the extent of these undesirable effects and subsequently develop testing techniques to eliminate them was imposed on the aerodynamic community. The challenges to the ascent aerodynamics community documented are unique due to the aerodynamic complexity of the Shuttle launch. Never before was such a complex vehicle aerodynamically characterized. The challenges were met with innovative engineering analyses/methodology development and wind tunnel testing techniques.

Combining Modeling and Gaming for Predictive Analytics

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

Riensche, Roderick M.; Whitney, Paul D.

2012-08-22

Many of our most significant challenges involve people. While human behavior has long been studied, there are recent advances in computational modeling of human behavior. With advances in computational capabilities come increases in the volume and complexity of data that humans must understand in order to make sense of and capitalize on these modeling advances. Ultimately, models represent an encapsulation of human knowledge. One inherent challenge in modeling is efficient and accurate transfer of knowledge from humans to models, and subsequent retrieval. The simulated real-world environment of games presents one avenue for these knowledge transfers. In this paper we describemore » our approach of combining modeling and gaming disciplines to develop predictive capabilities, using formal models to inform game development, and using games to provide data for modeling.« less

Challenges and priorities for modelling livestock health and pathogens in the context of climate change

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

Özkan, Şeyda

Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire basedmore » exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can help focus the development of modelling capacity and future research structures in this vital field. Well-funded networks capable of managing the long-term development of shared resources are required in order to create a cohesive modelling community equipped to tackle the complex challenges of climate change. - Highlights: • Experts identified challenges for health and pathogen modelling under climate change. • Eighteen key challenges and associated research priorities were identified. • Increasing capacity will require improved organisation and sharing knowledge. • Better communication across the diverse topics and approaches in this field is needed.« less

Summary of the DREAM8 Parameter Estimation Challenge: Toward Parameter Identification for Whole-Cell Models.

PubMed

Karr, Jonathan R; Williams, Alex H; Zucker, Jeremy D; Raue, Andreas; Steiert, Bernhard; Timmer, Jens; Kreutz, Clemens; Wilkinson, Simon; Allgood, Brandon A; Bot, Brian M; Hoff, Bruce R; Kellen, Michael R; Covert, Markus W; Stolovitzky, Gustavo A; Meyer, Pablo

2015-05-01

Whole-cell models that explicitly represent all cellular components at the molecular level have the potential to predict phenotype from genotype. However, even for simple bacteria, whole-cell models will contain thousands of parameters, many of which are poorly characterized or unknown. New algorithms are needed to estimate these parameters and enable researchers to build increasingly comprehensive models. We organized the Dialogue for Reverse Engineering Assessments and Methods (DREAM) 8 Whole-Cell Parameter Estimation Challenge to develop new parameter estimation algorithms for whole-cell models. We asked participants to identify a subset of parameters of a whole-cell model given the model's structure and in silico "experimental" data. Here we describe the challenge, the best performing methods, and new insights into the identifiability of whole-cell models. We also describe several valuable lessons we learned toward improving future challenges. Going forward, we believe that collaborative efforts supported by inexpensive cloud computing have the potential to solve whole-cell model parameter estimation.

Staying Connected: Sustaining Collaborative Care Models with Limited Funding.

PubMed

Johnston, Brenda J; Peppard, Lora; Newton, Marian

2015-08-01

Providing psychiatric services in the primary care setting is challenging. The multidisciplinary, coordinated approach of collaborative care models (CCMs) addresses these challenges. The purpose of the current article is to discuss the implementation of a CCM at a free medical clinic (FMC) where volunteer staff provide the majority of services. Essential components of CCMs include (a) comprehensive screening and assessment, (b) shared development and communication of care plans among providers and the patient, and (c) care coordination and management. Challenges to implementing and sustaining a CCM at a FMC in Virginia attempting to meet the medical and psychiatric needs of the underserved are addressed. Although the CCM produced favorable outcomes, sustaining the model long-term presented many challenges. Strategies for addressing these challenges are discussed. Copyright 2015, SLACK Incorporated.

Development of a Rift Valley fever virus viremia challenge model in sheep and goats

USDA-ARS?s Scientific Manuscript database

Rift valley fever virus (RVFV), a member of the family Bunyaviridae, causes severe to fatal disease in newborn ruminants, as well as abortions in pregnant animals; both preventable by vaccination. Availability of a challenge model is a pre-requisite for vaccine efficacy trials. Several modes of ino...

Influenza Vaccinations, Fall 2009: Model School-Located Vaccination Clinics

ERIC Educational Resources Information Center

Herl Jenlink, Carolyn; Kuehnert, Paul; Mazyck, Donna

2010-01-01

The 2009 H1N1 influenza virus presented a major challenge to health departments, schools, and other community partners to effectively vaccinate large numbers of Americans, primarily children. The use of school-located vaccination (SLV) programs to address this challenge led health departments and schools to become creative in developing models for…

Improving College and Career Readiness through Challenge-Based Learning

ERIC Educational Resources Information Center

Shuptrine, Carl

2013-01-01

High school students in an Advanced Video class addressed the challenge of increasing community awareness. Students followed a challenge-based learning model developing guiding questions and activities to determine solutions for implementation. Literature supported the use of project-based learning that fostered partnerships outside of the…

Evaluating the impacts of agricultural land management practices: A probabilistic hydrologic modeling approach

USDA-ARS?s Scientific Manuscript database

The complexity of the hydrologic system challenges the development of models. One issue faced during the model development stage is the uncertainty involved in model parameterization. Using a single optimized set of parameters (one snapshot) to represent baseline conditions of the system limits the ...

Development of a Human Neurovascular Unit Organotypic Systems Model of Early Brain Development

EPA Science Inventory

The inability to model human brain and blood-brain barrier development in vitro poses a major challenge in studies of how chemicals impact early neurogenic periods. During human development, disruption of thyroid hormone (TH) signaling is related to adverse morphological effects ...

An Outpatient, Ambulant-Design, Controlled Human Infection Model Using Escalating Doses of Salmonella Typhi Challenge Delivered in Sodium Bicarbonate Solution

PubMed Central

Waddington, Claire S.; Darton, Thomas C.; Jones, Claire; Haworth, Kathryn; Peters, Anna; John, Tessa; Thompson, Ben A. V.; Kerridge, Simon A.; Kingsley, Robert A.; Zhou, Liqing; Holt, Kathryn E.; Yu, Ly-Mee; Lockhart, Stephen; Farrar, Jeremy J.; Sztein, Marcelo B.; Dougan, Gordon; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.

2014-01-01

Background. Typhoid fever is a major global health problem, the control of which is hindered by lack of a suitable animal model in which to study Salmonella Typhi infection. Until 1974, a human challenge model advanced understanding of typhoid and was used in vaccine development. We set out to establish a new human challenge model and ascertain the S. Typhi (Quailes strain) inoculum required for an attack rate of 60%–75% in typhoid-naive volunteers when ingested with sodium bicarbonate solution. Methods. Groups of healthy consenting adults ingested escalating dose levels of S. Typhi and were closely monitored in an outpatient setting for 2 weeks. Antibiotic treatment was initiated if typhoid diagnosis occurred (temperature ≥38°C sustained ≥12 hours or bacteremia) or at day 14 in those remaining untreated. Results. Two dose levels (103 or 104 colony-forming units) were required to achieve the primary objective, resulting in attack rates of 55% (11/20) or 65% (13/20), respectively. Challenge was well tolerated; 4 of 40 participants fulfilled prespecified criteria for severe infection. Most diagnoses (87.5%) were confirmed by blood culture, and asymptomatic bacteremia and stool shedding of S. Typhi was also observed. Participants who developed typhoid infection demonstrated serological responses to flagellin and lipopolysaccharide antigens by day 14; however, no anti-Vi antibody responses were detected. Conclusions. Human challenge with a small inoculum of virulent S. Typhi administered in bicarbonate solution can be performed safely using an ambulant-model design to advance understanding of host–pathogen interactions and immunity. This model should expedite development of diagnostics, vaccines, and therapeutics for typhoid control. PMID:24519873

The big challenges in modeling human and environmental well-being.

PubMed

Tuljapurkar, Shripad

2016-01-01

This article is a selective review of quantitative research, historical and prospective, that is needed to inform sustainable development policy. I start with a simple framework to highlight how demography and productivity shape human well-being. I use that to discuss three sets of issues and corresponding challenges to modeling: first, population prehistory and early human development and their implications for the future; second, the multiple distinct dimensions of human and environmental well-being and the meaning of sustainability; and, third, inequality as a phenomenon triggered by development and models to examine changing inequality and its consequences. I conclude with a few words about other important factors: political, institutional, and cultural.

Fluid-Structure Interaction Modeling of Parachutes with Disreefing and Modified Geometric Porosity and Separation Aerodynamics of a Cover Jettisoned to the Spacecraft Wake

NASA Astrophysics Data System (ADS)

Fritze, Matthew D.

Fluid-structure interaction (FSI) modeling of spacecraft parachutes involves a number of computational challenges. The canopy complexity created by the hundreds of gaps and slits and design-related modification of that geometric porosity by removal of some of the sails and panels are among the formidable challenges. Disreefing from one stage to another when the parachute is used in multiple stages is another formidable challenge. This thesis addresses the computational challenges involved in disreefing of spacecraft parachutes and fully-open and reefed stages of the parachutes with modified geometric porosity. The special techniques developed to address these challenges are described and the FSI computations are be reported. The thesis also addresses the modeling and computation challenges involved in very early stages, where the sudden separation of a cover jettisoned to the spacecraft wake needs to be modeled. Higher-order temporal representations used in modeling the separation motion are described, and the computed separation and wake-induced forces acting on the cover are reported.

Model-based nonlinear control of hydraulic servo systems: Challenges, developments and perspectives

NASA Astrophysics Data System (ADS)

Yao, Jianyong

2018-06-01

Hydraulic servo system plays a significant role in industries, and usually acts as a core point in control and power transmission. Although linear theory-based control methods have been well established, advanced controller design methods for hydraulic servo system to achieve high performance is still an unending pursuit along with the development of modern industry. Essential nonlinearity is a unique feature and makes model-based nonlinear control more attractive, due to benefit from prior knowledge of the servo valve controlled hydraulic system. In this paper, a discussion for challenges in model-based nonlinear control, latest developments and brief perspectives of hydraulic servo systems are presented: Modelling uncertainty in hydraulic system is a major challenge, which includes parametric uncertainty and time-varying disturbance; some specific requirements also arise ad hoc difficulties such as nonlinear friction during low velocity tracking, severe disturbance, periodic disturbance, etc.; to handle various challenges, nonlinear solutions including parameter adaptation, nonlinear robust control, state and disturbance observation, backstepping design and so on, are proposed and integrated, theoretical analysis and lots of applications reveal their powerful capability to solve pertinent problems; and at the end, some perspectives and associated research topics (measurement noise, constraints, inner valve dynamics, input nonlinearity, etc.) in nonlinear hydraulic servo control are briefly explored and discussed.

Towards integrated solutions for water, energy, and land using an integrated nexus modeling framework

NASA Astrophysics Data System (ADS)

Wada, Y.

2017-12-01

Humanity has already reached or even exceeded the Earth's carrying capacity. Growing needs for food, energy and water will only exacerbate existing challenges over the next decades. Consequently, the acceptance of "business as usual" is eroding and we are being challenged to adopt new, more integrated, and more inclusive development pathways that avoid dangerous interference with the local environment and global planetary boundaries. This challenge is embodied in the United Nation's Sustainable Development Goals (SDGs), which endeavor to set a global agenda for moving towards more sustainable development strategies. To improve and sustain human welfare, it is critical that access to modern, reliable, and affordable water, energy, and food is expanded and maintained. The Integrated Solutions for Water, Energy, and Land (IS-WEL) project has been launched by IIASA, together with the Global Environment Facility (GEF) and the United Nations Industrial Development Organization (UNIDO). This project focuses on the water-energy-land nexus in the context of other major global challenges such as urbanization, environmental degradation, and equitable and sustainable futures. It develops a consistent framework for looking at the water-energy-land nexus and identify strategies for achieving the needed transformational outcomes through an advanced assessment framework. A multi-scalar approach are being developed that aims to combine global and regional integrated assessment tools with local stakeholder knowledge in order to identify robust solutions to energy, water, food, and ecosystem security in selected regions of the world. These are regions facing multiple energy, water and land use challenges and rapid demographic and economic changes, and are hardest hit by increasing climate variability and change. This project combines the global integrated assessment model (MESSAGE) with the global land (GLOBIOM) and water (Community Water Model) model respectively, and the integrated modeling framework are then combined with detailed regional decision support tools for water-energy-land nexus analysis in case study regions. A number of stakeholder meetings are used to engage local communities in the definition of important nexus drivers, scenario development and definition of performance metrics.

Collaborative Modeling: Experience of the U.S. Preventive Services Task Force.

PubMed

Petitti, Diana B; Lin, Jennifer S; Owens, Douglas K; Croswell, Jennifer M; Feuer, Eric J

2018-01-01

Models can be valuable tools to address uncertainty, trade-offs, and preferences when trying to understand the effects of interventions. Availability of results from two or more independently developed models that examine the same question (comparative modeling) allows systematic exploration of differences between models and the effect of these differences on model findings. Guideline groups sometimes commission comparative modeling to support their recommendation process. In this commissioned collaborative modeling, modelers work with the people who are developing a recommendation or policy not only to define the questions to be addressed but ideally, work side-by-side with each other and with systematic reviewers to standardize selected inputs and incorporate selected common assumptions. This paper describes the use of commissioned collaborative modeling by the U.S. Preventive Services Task Force (USPSTF), highlighting the general challenges and opportunities encountered and specific challenges for some topics. It delineates other approaches to use modeling to support evidence-based recommendations and the many strengths of collaborative modeling compared with other approaches. Unlike systematic reviews prepared for the USPSTF, the commissioned collaborative modeling reports used by the USPSTF in making recommendations about screening have not been required to follow a common format, sometimes making it challenging to understand key model features. This paper presents a checklist developed to critically appraise commissioned collaborative modeling reports about cancer screening topics prepared for the USPSTF. Copyright © 2017 American Journal of Preventive Medicine. All rights reserved.

Preclinical Mouse Cancer Models: A Maze of Opportunities and Challenges

PubMed Central

Day, Chi-Ping; Merlino, Glenn; Van Dyke, Terry

2015-01-01

Significant advances have been made in developing novel therapeutics for cancer treatment, and targeted therapies have revolutionized the treatment of some cancers. Despite the promise, only about five percent of new cancer drugs are approved, and most fail due to lack of efficacy. The indication is that current preclinical methods are limited in predicting successful outcomes. Such failure exacts enormous cost, both financial and in the quality of human life. This primer explores the current status, promise and challenges of preclinical evaluation in advanced mouse cancer models and briefly addresses emerging models for early-stage preclinical development. PMID:26406370

Leadership Identity Development: Challenges in Applying a Developmental Model

ERIC Educational Resources Information Center

Komives, Susan R.; Longerbeam, Susan D.; Mainella, Felicia; Osteen, Laura; Owen, Julie E.; Wagner, Wendy

2009-01-01

The leadership identity development (LID) grounded theory (Komives, Owen, Longerbeam, Mainella, & Osteen, 2005) and related LID model (Komives, Longerbeam, Owen, Mainella, & Osteen, 2006) present a framework for understanding how individual college students develop the social identity of being collaborative, relational leaders…

Summary of the DREAM8 Parameter Estimation Challenge: Toward Parameter Identification for Whole-Cell Models

PubMed Central

Karr, Jonathan R.; Williams, Alex H.; Zucker, Jeremy D.; Raue, Andreas; Steiert, Bernhard; Timmer, Jens; Kreutz, Clemens; Wilkinson, Simon; Allgood, Brandon A.; Bot, Brian M.; Hoff, Bruce R.; Kellen, Michael R.; Covert, Markus W.; Stolovitzky, Gustavo A.; Meyer, Pablo

2015-01-01

Whole-cell models that explicitly represent all cellular components at the molecular level have the potential to predict phenotype from genotype. However, even for simple bacteria, whole-cell models will contain thousands of parameters, many of which are poorly characterized or unknown. New algorithms are needed to estimate these parameters and enable researchers to build increasingly comprehensive models. We organized the Dialogue for Reverse Engineering Assessments and Methods (DREAM) 8 Whole-Cell Parameter Estimation Challenge to develop new parameter estimation algorithms for whole-cell models. We asked participants to identify a subset of parameters of a whole-cell model given the model’s structure and in silico “experimental” data. Here we describe the challenge, the best performing methods, and new insights into the identifiability of whole-cell models. We also describe several valuable lessons we learned toward improving future challenges. Going forward, we believe that collaborative efforts supported by inexpensive cloud computing have the potential to solve whole-cell model parameter estimation. PMID:26020786

Safety assessment of immunomodulatory biologics: the promise and challenges of regulatory T-cell modulation.

PubMed

Ponce, Rafael A

2011-01-01

Regulatory T-cell (T(reg)) modulation is developing as an important therapeutic opportunity for the treatment of a number of important diseases, including cancer, autoimmunity, infection, and organ transplant rejection. However, as demonstrated with IL-2 and TGN-1412, our understanding of the complex immunological interactions that occur with T(reg) modulation in both non-clinical models and in patients remains limited and appears highly contextual. This lack of understanding will challenge our ability to identify the patient population who might derive the highest benefit from T(reg) modulation and creates special challenges as we transition these therapeutics from non-clinical models into humans. Thus, in vivo testing in the most representative animal model systems, with careful progress in the clinic, will remain critical in developing therapeutics targeting T(reg) and understanding their clinical utility. Moreover, toxicology models can inform some of the potential liabilities associated with T(reg) modulation, but not all, suggesting a continued need to explore and validate predictive models.

The physicochemical process of bacterial attachment to abiotic surfaces: Challenges for mechanistic studies, predictability and the development of control strategies.

PubMed

Wang, Yi; Lee, Sui Mae; Dykes, Gary

2015-01-01

Bacterial attachment to abiotic surfaces can be explained as a physicochemical process. Mechanisms of the process have been widely studied but are not yet well understood due to their complexity. Physicochemical processes can be influenced by various interactions and factors in attachment systems, including, but not limited to, hydrophobic interactions, electrostatic interactions and substratum surface roughness. Mechanistic models and control strategies for bacterial attachment to abiotic surfaces have been established based on the current understanding of the attachment process and the interactions involved. Due to a lack of process control and standardization in the methodologies used to study the mechanisms of bacterial attachment, however, various challenges are apparent in the development of models and control strategies. In this review, the physicochemical mechanisms, interactions and factors affecting the process of bacterial attachment to abiotic surfaces are described. Mechanistic models established based on these parameters are discussed in terms of their limitations. Currently employed methods to study these parameters and bacterial attachment are critically compared. The roles of these parameters in the development of control strategies for bacterial attachment are reviewed, and the challenges that arise in developing mechanistic models and control strategies are assessed.

CHALLENGES OF PROCESSING BIOLOGICAL DATA FOR INCORPORATION INTO A LAKE EUTROPHICATION MODEL

EPA Science Inventory

A eutrophication model is in development as part of the Lake Michigan Mass Balance Project (LMMBP). Successful development and calibration of this model required the processing and incorporation of extensive biological data. Data were drawn from multiple sources, including nutrie...

Testing the Sarcocystis neurona vaccine using an equine protozoal myeloencephalitis challenge model.

PubMed

Saville, William J A; Dubey, Jitender P; Marsh, Antoinette E; Reed, Stephen M; Keene, Robert O; Howe, Daniel K; Morrow, Jennifer; Workman, Jeffrey D

2017-11-30

Equine protozoal myeloencephalitis (EPM) is an important equine neurologic disorder, and treatments for the disease are often unrewarding. Prevention of the disease is the most important aspect for EPM, and a killed vaccine was previously developed for just that purpose. Evaluation of the vaccine had been hampered by lack of post vaccination challenge. The purpose of this study was to determine if the vaccine could prevent development of clinical signs after challenge with Sarcocystis neurona sporocysts in an equine challenge model. Seventy horses that were negative for antibodies to S. neurona and were neurologically normal were randomly assigned to vaccine or placebo groups and divided into short-term duration of immunity (study #1) and long-term duration of immunity (study #2) studies. S. neurona sporocysts used for the challenge were generated in the opossum/raccoon cycle isolate SN 37-R. Study #1 horses received an initial vaccination and a booster, and were challenged 34days post second vaccination. Study #2 horses received a vaccination and two boosters and were challenged 139days post third vaccination. All horses in study #1 developed neurologic signs (n=30) and there was no difference between the vaccinates and controls (P=0.7683). All but four horses in study #2 developed detectable neurologic deficits. The neurologic signs, although not statistically significant, were worse in the vaccinated horses (P=0.1559). In these two studies, vaccination with the S. neurona vaccine failed to prevent development of clinical neurologic deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

Economic analysis of model validation for a challenge problem

DOE PAGES

Paez, Paul J.; Paez, Thomas L.; Hasselman, Timothy K.

2016-02-19

It is now commonplace for engineers to build mathematical models of the systems they are designing, building, or testing. And, it is nearly universally accepted that phenomenological models of physical systems must be validated prior to use for prediction in consequential scenarios. Yet, there are certain situations in which testing only or no testing and no modeling may be economically viable alternatives to modeling and its associated testing. This paper develops an economic framework within which benefit–cost can be evaluated for modeling and model validation relative to other options. The development is presented in terms of a challenge problem. Asmore » a result, we provide a numerical example that quantifies when modeling, calibration, and validation yield higher benefit–cost than a testing only or no modeling and no testing option.« less

Mathematics applied to the climate system: outstanding challenges and recent progress

PubMed Central

Williams, Paul D.; Cullen, Michael J. P.; Davey, Michael K.; Huthnance, John M.

2013-01-01

The societal need for reliable climate predictions and a proper assessment of their uncertainties is pressing. Uncertainties arise not only from initial conditions and forcing scenarios, but also from model formulation. Here, we identify and document three broad classes of problems, each representing what we regard to be an outstanding challenge in the area of mathematics applied to the climate system. First, there is the problem of the development and evaluation of simple physically based models of the global climate. Second, there is the problem of the development and evaluation of the components of complex models such as general circulation models. Third, there is the problem of the development and evaluation of appropriate statistical frameworks. We discuss these problems in turn, emphasizing the recent progress made by the papers presented in this Theme Issue. Many pressing challenges in climate science require closer collaboration between climate scientists, mathematicians and statisticians. We hope the papers contained in this Theme Issue will act as inspiration for such collaborations and for setting future research directions. PMID:23588054

Challenging the Paradigm: Notes on Developing an Indigenized Teacher Education Curriculum

ERIC Educational Resources Information Center

Gopinathan, S.

2006-01-01

While considerable attention is being paid to reforming education systems to prepare students for the challenges of globalization and a knowledge-based economy, teacher education models in the Asia Pacific remain insufficiently critiqued. There is an urgent need to rethink teacher education as, in spite of decades of investment and development,…

Challenges and priorities for modelling livestock health and pathogens in the context of climate change.

PubMed

Özkan, Şeyda; Vitali, Andrea; Lacetera, Nicola; Amon, Barbara; Bannink, André; Bartley, Dave J; Blanco-Penedo, Isabel; de Haas, Yvette; Dufrasne, Isabelle; Elliott, John; Eory, Vera; Fox, Naomi J; Garnsworthy, Phil C; Gengler, Nicolas; Hammami, Hedi; Kyriazakis, Ilias; Leclère, David; Lessire, Françoise; Macleod, Michael; Robinson, Timothy P; Ruete, Alejandro; Sandars, Daniel L; Shrestha, Shailesh; Stott, Alistair W; Twardy, Stanislaw; Vanrobays, Marie-Laure; Ahmadi, Bouda Vosough; Weindl, Isabelle; Wheelhouse, Nick; Williams, Adrian G; Williams, Hefin W; Wilson, Anthony J; Østergaard, Søren; Kipling, Richard P

2016-11-01

Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can help focus the development of modelling capacity and future research structures in this vital field. Well-funded networks capable of managing the long-term development of shared resources are required in order to create a cohesive modelling community equipped to tackle the complex challenges of climate change. Copyright © 2016 Elsevier Inc. All rights reserved.

Consensus Statement on Electronic Health Predictive Analytics: A Guiding Framework to Address Challenges

PubMed Central

Amarasingham, Ruben; Audet, Anne-Marie J.; Bates, David W.; Glenn Cohen, I.; Entwistle, Martin; Escobar, G. J.; Liu, Vincent; Etheredge, Lynn; Lo, Bernard; Ohno-Machado, Lucila; Ram, Sudha; Saria, Suchi; Schilling, Lisa M.; Shahi, Anand; Stewart, Walter F.; Steyerberg, Ewout W.; Xie, Bin

2016-01-01

Context: The recent explosion in available electronic health record (EHR) data is motivating a rapid expansion of electronic health care predictive analytic (e-HPA) applications, defined as the use of electronic algorithms that forecast clinical events in real time with the intent to improve patient outcomes and reduce costs. There is an urgent need for a systematic framework to guide the development and application of e-HPA to ensure that the field develops in a scientifically sound, ethical, and efficient manner. Objectives: Building upon earlier frameworks of model development and utilization, we identify the emerging opportunities and challenges of e-HPA, propose a framework that enables us to realize these opportunities, address these challenges, and motivate e-HPA stakeholders to both adopt and continuously refine the framework as the applications of e-HPA emerge. Methods: To achieve these objectives, 17 experts with diverse expertise including methodology, ethics, legal, regulation, and health care delivery systems were assembled to identify emerging opportunities and challenges of e-HPA and to propose a framework to guide the development and application of e-HPA. Findings: The framework proposed by the panel includes three key domains where e-HPA differs qualitatively from earlier generations of models and algorithms (Data Barriers, Transparency, and Ethics) and areas where current frameworks are insufficient to address the emerging opportunities and challenges of e-HPA (Regulation and Certification; and Education and Training). The following list of recommendations summarizes the key points of the framework: Data Barriers: Establish mechanisms within the scientific community to support data sharing for predictive model development and testing.Transparency: Set standards around e-HPA validation based on principles of scientific transparency and reproducibility.Ethics: Develop both individual-centered and society-centered risk-benefit approaches to evaluate e-HPA.Regulation and Certification: Construct a self-regulation and certification framework within e-HPA.Education and Training: Make significant changes to medical, nursing, and paraprofessional curricula by including training for understanding, evaluating, and utilizing predictive models. PMID:27141516

Consensus Statement on Electronic Health Predictive Analytics: A Guiding Framework to Address Challenges.

PubMed

Amarasingham, Ruben; Audet, Anne-Marie J; Bates, David W; Glenn Cohen, I; Entwistle, Martin; Escobar, G J; Liu, Vincent; Etheredge, Lynn; Lo, Bernard; Ohno-Machado, Lucila; Ram, Sudha; Saria, Suchi; Schilling, Lisa M; Shahi, Anand; Stewart, Walter F; Steyerberg, Ewout W; Xie, Bin

2016-01-01

The recent explosion in available electronic health record (EHR) data is motivating a rapid expansion of electronic health care predictive analytic (e-HPA) applications, defined as the use of electronic algorithms that forecast clinical events in real time with the intent to improve patient outcomes and reduce costs. There is an urgent need for a systematic framework to guide the development and application of e-HPA to ensure that the field develops in a scientifically sound, ethical, and efficient manner. Building upon earlier frameworks of model development and utilization, we identify the emerging opportunities and challenges of e-HPA, propose a framework that enables us to realize these opportunities, address these challenges, and motivate e-HPA stakeholders to both adopt and continuously refine the framework as the applications of e-HPA emerge. To achieve these objectives, 17 experts with diverse expertise including methodology, ethics, legal, regulation, and health care delivery systems were assembled to identify emerging opportunities and challenges of e-HPA and to propose a framework to guide the development and application of e-HPA. The framework proposed by the panel includes three key domains where e-HPA differs qualitatively from earlier generations of models and algorithms (Data Barriers, Transparency, and ETHICS) and areas where current frameworks are insufficient to address the emerging opportunities and challenges of e-HPA (Regulation and Certification; and Education and Training). The following list of recommendations summarizes the key points of the framework: Data Barriers: Establish mechanisms within the scientific community to support data sharing for predictive model development and testing.Transparency: Set standards around e-HPA validation based on principles of scientific transparency and reproducibility. Develop both individual-centered and society-centered risk-benefit approaches to evaluate e-HPA.Regulation and Certification: Construct a self-regulation and certification framework within e-HPA.Education and Training: Make significant changes to medical, nursing, and paraprofessional curricula by including training for understanding, evaluating, and utilizing predictive models.

Prenatal stress challenge impairs fetal lung development and asthma severity sex-specifically in mice.

PubMed

Zazara, Dimitra E; Perani, Clara V; Solano, María E; Arck, Petra C

2018-02-01

Allergic asthma is an increasing health problem worldwide. Interestingly, prenatal challenges such as stress have been associated with an increased risk for asthma during childhood. The underlying pathogenesis of how prenatal stress increases the risk for asthma still remains unclear. Potential targets could be that the fetal immune ontogeny or fetal lung development are compromised by prenatal challenges. Here, we aimed to identify whether prenatal stress challenge affects fetal lung development in mice. C57BL/6 pregnant mice were challenged with sound stress and fetal lung development was assessed histologically. Whilst prenatal stress challenge did not profoundly affect lung development in male fetuses, it resulted in less extensive terminal sacs, surrounded by thicker mesenchymal tissue in female fetuses. Thus, prenatal stress disrupted fetal lung development sex-specifically. Interestingly, upon prenatal stress challenge, the airway hyperresponsiveness and eosinophilic inflammation- two hallmarks of asthma - were significantly increased in adult female offspring, whilst regulatory CD4+ T cells were reduced. These findings strongly underpin the sex-specific association between s challenged fetal development and a sex-specific altered severity of asthma in adult offspring. Our model now allows to identify maternal markers through which the risk for asthma and possible other diseases is vertically transferred before birth in response to challenges. Such identification then opens avenues for primary disease prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Tendon Tissue Engineering: Progress, Challenges, and Translation to the Clinic

PubMed Central

Shearn, Jason T.; Kinneberg, Kirsten R.C.; Dyment, Nathaniel A.; Galloway, Marc T.; Kenter, Keith; Wylie, Christopher; Butler, David L.

2013-01-01

The tissue engineering field has made great strides in understanding how different aspects of tissue engineered constructs (TECs) and the culture process affect final tendon repair. However, there remain significant challenges in developing strategies that will lead to a clinically effective and commercially successful product. In an effort to increase repair quality, a better understanding of normal development, and how it differs from adult tendon healing, may provide strategies to improve tissue engineering. As tendon tissue engineering continues to improve, the field needs to employ more clinically relevant models of tendon injury such as degenerative tendons. We need to translate successes to larger animal models to begin exploring the clinical implications of our treatments. By advancing the models used to validate our TECs, we can help convince our toughest customer, the surgeon, that our products will be clinically efficacious. As we address these challenges in musculoskeletal tissue engineering, the field still needs to address the commercialization of products developed in the laboratory. TEC commercialization faces numerous challenges because each injury and patient is unique. This review aims to provide tissue engineers with a summary of important issues related to engineering tendon repairs and potential strategies for producing clinically successful products. PMID:21625053

A Computational Approach for Probabilistic Analysis of Water Impact Simulations

NASA Technical Reports Server (NTRS)

Horta, Lucas G.; Mason, Brian H.; Lyle, Karen H.

2009-01-01

NASA's development of new concepts for the Crew Exploration Vehicle Orion presents many similar challenges to those worked in the sixties during the Apollo program. However, with improved modeling capabilities, new challenges arise. For example, the use of the commercial code LS-DYNA, although widely used and accepted in the technical community, often involves high-dimensional, time consuming, and computationally intensive simulations. The challenge is to capture what is learned from a limited number of LS-DYNA simulations to develop models that allow users to conduct interpolation of solutions at a fraction of the computational time. This paper presents a description of the LS-DYNA model, a brief summary of the response surface techniques, the analysis of variance approach used in the sensitivity studies, equations used to estimate impact parameters, results showing conditions that might cause injuries, and concluding remarks.

Challenges of forest landscape modeling - simulating large landscapes and validating results

Treesearch

Hong S. He; Jian Yang; Stephen R. Shifley; Frank R. Thompson

2011-01-01

Over the last 20 years, we have seen a rapid development in the field of forest landscape modeling, fueled by both technological and theoretical advances. Two fundamental challenges have persisted since the inception of FLMs: (1) balancing realistic simulation of ecological processes at broad spatial and temporal scales with computing capacity, and (2) validating...

An aircraft model for the AIAA controls design challenge

NASA Technical Reports Server (NTRS)

Brumbaugh, Randal W.

1991-01-01

A generic, state-of-the-art, high-performance aircraft model, including detailed, full-envelope, nonlinear aerodynamics, and full-envelope thrust and first-order engine response data is described. While this model was primarily developed Controls Design Challenge, the availability of such a model provides a common focus for research in aeronautical control theory and methodology. An implementation of this model using the FORTRAN computer language, associated routines furnished with the aircraft model, and techniques for interfacing these routines to external procedures is also described. Figures showing vehicle geometry, surfaces, and sign conventions are included.

Prophylaxis of Plasmodium falciparum Infection in a Human Challenge Model with WR 238605, a New 8-Aminoquinoline Antimalarial

PubMed Central

Brueckner, Ralf P.; Coster, Trinka; Wesche, David L.; Shmuklarsky, Moshe; Schuster, Brian G.

1998-01-01

The prophylactic efficacy of WR 238605, a primaquine analog, was studied with a human Plasmodium falciparum challenge model. A single oral dose of 600 mg, administered 1 day prior to challenge, successfully protected three of four subjects. The fourth subject developed mild, oligosymptomatic malaria on day 31, with drug concentrations one-half of those in the protected individuals. WR 238605 appears to be a promising prophylactic drug for P. falciparum malaria. PMID:9593172

Development of Unique Advanced Medical Research and Development Initiatives in the Western United States and Pacific Rim

DTIC Science & Technology

2012-11-01

funding). Funding from the TATRC/Qualcomm innovation challenge allowed the vLC to expand its TAP (Technology Acceleration Program) model to the...innovative research challenges and pilot projects. Relevance: This research effort to build partnerships and collaborations has significant benefit to...the proposal was Specific research under task 2 of this award has been the following: 1) “Grand Challenge ” in Military Medicine Research, 2) Packaging

Cancer Nanotechnology Startup Challenge: a new way to realize the fruits of innovation.

PubMed

Currell, Fred; Bellringer, Mark

A significant new innovation-development model is being launched in the field of cancer and nanotechnology. A significant new innovation-development model is being launched in the field of cancer and nanotechnology.

Integrating science and business models of sustainability for environmentally-challenging industries such as secondary lead smelters: a systematic review and analysis of findings.

PubMed

Genaidy, A M; Sequeira, R; Tolaymat, T; Kohler, J; Wallace, S; Rinder, M

2010-09-01

Secondary lead smelters (SLS) represent an environmentally-challenging industry as they deal with toxic substances posing potential threats to both human and environmental health, consequently, they operate under strict government regulations. Such challenges have resulted in the significant reduction of SLS plants in the last three decades. In addition, the domestic recycling of lead has been on a steep decline in the past 10 years as the amount of lead recovered has remained virtually unchanged while consumption has increased. Therefore, one may wonder whether sustainable development can be achieved among SLS. The primary objective of this study was to determine whether a roadmap for sustainable development can be established for SLS. The following aims were established in support of the study objective: (1) to conduct a systematic review and an analysis of models of sustainable systems with a particular emphasis on SLS; (2) to document the challenges for the U.S. secondary lead smelting industry; and (3) to explore practices and concepts which act as vehicles for SLS on the road to sustainable development. An evidence-based methodology was adopted to achieve the study objective. A comprehensive electronic search was conducted to implement the aforementioned specific aims. Inclusion criteria were established to filter out irrelevant scientific papers and reports. The relevant articles were closely scrutinized and appraised to extract the required information and data for the possible development of a sustainable roadmap. The search process yielded a number of research articles which were utilized in the systematic review. Two types of models emerged: management/business and science/mathematical models. Although the management/business models explored actions to achieve sustainable growth in the industrial enterprise, science/mathematical models attempted to explain the sustainable behaviors and properties aiming at predominantly ecosystem management. As such, there are major disconnects between the science/mathematical and management/business models in terms of aims and goals. Therefore, there is an urgent need to integrate science and business models of sustainability for the industrial enterprises at large and environmentally-challenging industrial sectors in particular. In this paper, we offered examples of practices and concepts which can be used in charting a path towards sustainable development for secondary lead smelters particularly that the waste generated is much greater outside the industrial enterprise than inside. An environmentally-challenging industry such as secondary lead smelters requires a fresh look to chart a path towards sustainable development (i.e., survivability and purposive needs) for all stakeholders (i.e., industrial enterprise, individual stakeholders, and social/ecological systems). Such a path should deal with issues beyond pollution prevention, product stewardship and clean technologies. 2010 Elsevier Ltd. All rights reserved.

Developing Tomorrow's Integrated Community Health Systems: A Leadership Challenge for Public Health and Primary Care

PubMed Central

Welton, William E.; Kantner, Theodore A.; Katz, Sheila Moriber

1997-01-01

As the nation's health system moves away from earlier models to one grounded in population health and market-based systems of care, new challenges arise for public health professionals, primary care practitioners, health plan and institutional managers, and community leaders. Among the challenges are the need to develop creative concepts of organization and accountability and to assure that dynamic, system-oriented structures support the new kind of leadership that is required. Developing tomorrow's integrated community health systems will challenge the leadership skills and integrative abilities of public health professionals, primary care practitioners, and managers. These leaders and their new organizations must, in turn, assume increased accountability for improving community health. PMID:9184684

Experimental models in vaccine research: malaria and leishmaniasis.

PubMed

Teixeira, C; Gomes, R

2013-02-01

Animal models have a long history of being useful tools, not only to test and select vaccines, but also to help understand the elaborate details of the immune response that follows infection. Different models have been extensively used to investigate putative immunological correlates of protection against parasitic diseases that are important to reach a successful vaccine. The greatest challenge has been the improvement and adaptation of these models to reflect the reality of human disease and the screening of vaccine candidates capable of overcoming the challenge of natural transmission. This review will discuss the advantages and challenges of using experimental animal models for vaccine development and how the knowledge achieved can be extrapolated to human disease by looking into two important parasitic diseases: malaria and leishmaniasis.

Exploring a model-driven architecture (MDA) approach to health care information systems development.

PubMed

Raghupathi, Wullianallur; Umar, Amjad

2008-05-01

To explore the potential of the model-driven architecture (MDA) in health care information systems development. An MDA is conceptualized and developed for a health clinic system to track patient information. A prototype of the MDA is implemented using an advanced MDA tool. The UML provides the underlying modeling support in the form of the class diagram. The PIM to PSM transformation rules are applied to generate the prototype application from the model. The result of the research is a complete MDA methodology to developing health care information systems. Additional insights gained include development of transformation rules and documentation of the challenges in the application of MDA to health care. Design guidelines for future MDA applications are described. The model has the potential for generalizability. The overall approach supports limited interoperability and portability. The research demonstrates the applicability of the MDA approach to health care information systems development. When properly implemented, it has the potential to overcome the challenges of platform (vendor) dependency, lack of open standards, interoperability, portability, scalability, and the high cost of implementation.

Applying the Rasch Model to Measure Acculturation Challenges Faced by Saudi Female Students in the United States

ERIC Educational Resources Information Center

Hakami, Samah Mohammed

2012-01-01

The purpose of this study was to explore the major acculturation challenges faced by Saudi female students who study in the U.S. and to develop a scale to measure potential acculturation challenges. The construction of the scale was based on a table of specification that included nine domains of possible acculturation challenges: (a)…

Web based collaborative decision making in flood risk management

NASA Astrophysics Data System (ADS)

Evers, Mariele; Almoradie, Adrian; Jonoski, Andreja

2014-05-01

Stakeholder participation in the development of flood risk management (FRM) plans is essential since stakeholders often have a better understanding or knowledge of the potentials and limitation of their local area. Moreover, a participatory approach also creates trust amongst stakeholders, leading to a successful implementation of measures. Stakeholder participation however has its challenges and potential pitfalls that could lead to its premature termination. Such challenges and pitfalls are the limitation of financial resources, stakeholders' spatial distribution and their interest to participate. Different type of participation in FRM may encounter diverse challenges. These types of participation in FRM can be classified into (1) Information and knowledge sharing (IKS), (2) Consultative participation (CP) or (3) Collaborative decision making (CDM)- the most challenging type of participation. An innovative approach to address these challenges and potential pitfalls is a web-based mobile or computer-aided environment for stakeholder participation. This enhances the remote interaction between participating entities such as stakeholders. This paper presents a developed framework and an implementation of CDM web based environment for the Alster catchment (Hamburg, Germany) and Cranbrook catchment (London, UK). The CDM framework consists of two main stages: (1) Collaborative modelling and (2) Participatory decision making. This paper also highlights the stakeholder analyses, modelling approach and application of General Public License (GPL) technologies in developing the web-based environments. Actual test and evaluation of the environments was through series of stakeholders workshops. The overall results based from stakeholders' evaluation shows that web-based environments can address the challenges and potential pitfalls in stakeholder participation and it enhances participation in flood risk management. The web-based environment was developed within the DIANE-CM project (Decentralised Integrated Analysis and Enhancement of Awareness through Collaborative Modelling and Management of Flood Risk) of the 2nd ERANET CRUE funding initiative.

Evolving Non-Dominated Parameter Sets for Computational Models from Multiple Experiments

NASA Astrophysics Data System (ADS)

Lane, Peter C. R.; Gobet, Fernand

2013-03-01

Creating robust, reproducible and optimal computational models is a key challenge for theorists in many sciences. Psychology and cognitive science face particular challenges as large amounts of data are collected and many models are not amenable to analytical techniques for calculating parameter sets. Particular problems are to locate the full range of acceptable model parameters for a given dataset, and to confirm the consistency of model parameters across different datasets. Resolving these problems will provide a better understanding of the behaviour of computational models, and so support the development of general and robust models. In this article, we address these problems using evolutionary algorithms to develop parameters for computational models against multiple sets of experimental data; in particular, we propose the `speciated non-dominated sorting genetic algorithm' for evolving models in several theories. We discuss the problem of developing a model of categorisation using twenty-nine sets of data and models drawn from four different theories. We find that the evolutionary algorithms generate high quality models, adapted to provide a good fit to all available data.

Challenges and Advances for Genetic Engineering of Non-model Bacteria and Uses in Consolidated Bioprocessing

PubMed Central

Yan, Qiang; Fong, Stephen S.

2017-01-01

Metabolic diversity in microorganisms can provide the basis for creating novel biochemical products. However, most metabolic engineering projects utilize a handful of established model organisms and thus, a challenge for harnessing the potential of novel microbial functions is the ability to either heterologously express novel genes or directly utilize non-model organisms. Genetic manipulation of non-model microorganisms is still challenging due to organism-specific nuances that hinder universal molecular genetic tools and translatable knowledge of intracellular biochemical pathways and regulatory mechanisms. However, in the past several years, unprecedented progress has been made in synthetic biology, molecular genetics tools development, applications of omics data techniques, and computational tools that can aid in developing non-model hosts in a systematic manner. In this review, we focus on concerns and approaches related to working with non-model microorganisms including developing molecular genetics tools such as shuttle vectors, selectable markers, and expression systems. In addition, we will discuss: (1) current techniques in controlling gene expression (transcriptional/translational level), (2) advances in site-specific genome engineering tools [homologous recombination (HR) and clustered regularly interspaced short palindromic repeats (CRISPR)], and (3) advances in genome-scale metabolic models (GSMMs) in guiding design of non-model species. Application of these principles to metabolic engineering strategies for consolidated bioprocessing (CBP) will be discussed along with some brief comments on foreseeable future prospects. PMID:29123506

Models of Community Colleges in Mainland China

ERIC Educational Resources Information Center

Zhang, Yi

2017-01-01

This chapter provides an overview of community colleges in mainland China, addressing briefly the recent history of community college development, defining these institutions, detailing various models with examples, and discussing challenges faced by these institutions and recommendations for future development.

Challenges in Soft Computing: Case Study with Louisville MSD CSO Modeling

NASA Astrophysics Data System (ADS)

Ormsbee, L.; Tufail, M.

2005-12-01

The principal constituents of soft computing include fuzzy logic, neural computing, evolutionary computation, machine learning, and probabilistic reasoning. There are numerous applications of these constituents (both individually and combination of two or more) in the area of water resources and environmental systems. These range from development of data driven models to optimal control strategies to assist in more informed and intelligent decision making process. Availability of data is critical to such applications and having scarce data may lead to models that do not represent the response function over the entire domain. At the same time, too much data has a tendency to lead to over-constraining of the problem. This paper will describe the application of a subset of these soft computing techniques (neural computing and genetic algorithms) to the Beargrass Creek watershed in Louisville, Kentucky. The application include development of inductive models as substitutes for more complex process-based models to predict water quality of key constituents (such as dissolved oxygen) and use them in an optimization framework for optimal load reductions. Such a process will facilitate the development of total maximum daily loads for the impaired water bodies in the watershed. Some of the challenges faced in this application include 1) uncertainty in data sets, 2) model application, and 3) development of cause-and-effect relationships between water quality constituents and watershed parameters through use of inductive models. The paper will discuss these challenges and how they affect the desired goals of the project.

Challenges in Developing Models Describing Complex Soil Systems

NASA Astrophysics Data System (ADS)

Simunek, J.; Jacques, D.

2014-12-01

Quantitative mechanistic models that consider basic physical, mechanical, chemical, and biological processes have the potential to be powerful tools to integrate our understanding of complex soil systems, and the soil science community has often called for models that would include a large number of these diverse processes. However, once attempts have been made to develop such models, the response from the community has not always been overwhelming, especially after it discovered that these models are consequently highly complex, requiring not only a large number of parameters, not all of which can be easily (or at all) measured and/or identified, and which are often associated with large uncertainties, but also requiring from their users deep knowledge of all/most of these implemented physical, mechanical, chemical and biological processes. Real, or perceived, complexity of these models then discourages users from using them even for relatively simple applications, for which they would be perfectly adequate. Due to the nonlinear nature and chemical/biological complexity of the soil systems, it is also virtually impossible to verify these types of models analytically, raising doubts about their applicability. Code inter-comparisons, which is then likely the most suitable method to assess code capabilities and model performance, requires existence of multiple models of similar/overlapping capabilities, which may not always exist. It is thus a challenge not only to developed models describing complex soil systems, but also to persuade the soil science community in using them. As a result, complex quantitative mechanistic models are still an underutilized tool in soil science research. We will demonstrate some of the challenges discussed above on our own efforts in developing quantitative mechanistic models (such as HP1/2) for complex soil systems.

Education for Sustainable Development in Chemistry--Challenges, Possibilities and Pedagogical Models in Finland and Elsewhere

ERIC Educational Resources Information Center

Juntunen, M. K.; Aksela, M. K.

2014-01-01

This article analyses Education for Sustainable Development (ESD) in chemistry by reviewing existing challenges and future possibilities on the levels of the teacher and the student. Pedagogical frameworks that are found eligible in practice are reviewed. Lesson themes that are suitable for implementing socioscientific issues (SSI) related to ESD…

NASA Langley Distributed Propulsion VTOL Tilt-Wing Aircraft Testing, Modeling, Simulation, Control, and Flight Test Development

NASA Technical Reports Server (NTRS)

Rothhaar, Paul M.; Murphy, Patrick C.; Bacon, Barton J.; Gregory, Irene M.; Grauer, Jared A.; Busan, Ronald C.; Croom, Mark A.

2014-01-01

Control of complex Vertical Take-Off and Landing (VTOL) aircraft traversing from hovering to wing born flight mode and back poses notoriously difficult modeling, simulation, control, and flight-testing challenges. This paper provides an overview of the techniques and advances required to develop the GL-10 tilt-wing, tilt-tail, long endurance, VTOL aircraft control system. The GL-10 prototype's unusual and complex configuration requires application of state-of-the-art techniques and some significant advances in wind tunnel infrastructure automation, efficient Design Of Experiments (DOE) tunnel test techniques, modeling, multi-body equations of motion, multi-body actuator models, simulation, control algorithm design, and flight test avionics, testing, and analysis. The following compendium surveys key disciplines required to develop an effective control system for this challenging vehicle in this on-going effort.

Key challenges in the development and implementation of telehealth projects.

PubMed

Joseph, Victor; West, Robert M; Shickle, Darren; Keen, Justin; Clamp, Susan

2011-01-01

A literature review was carried out to identify the key challenges in the implementation of telehealth. This was followed by a survey of organisations in England involved in telehealth projects in order to understand the challenges they faced. Ten of the 13 health or local authority organisations surveyed had telehealth projects and three were at the planning stage. The analysis revealed seven key challenges facing implementers of telehealth in England. Based on the findings from the literature review and the survey, a model was constructed and a checklist drawn up. The model contained the following elements: identifying issues, needs and partners; producing a strategy; securing funding; implementing changes; and monitoring and evaluating a telehealth project. The checklist was validated by using key informants from the organisations originally surveyed. The checklist may be useful to guide telehealth development and implementation in the future.

The Challenges of Credible Thermal Protection System Reliability Quantification

NASA Technical Reports Server (NTRS)

Green, Lawrence L.

2013-01-01

The paper discusses several of the challenges associated with developing a credible reliability estimate for a human-rated crew capsule thermal protection system. The process of developing such a credible estimate is subject to the quantification, modeling and propagation of numerous uncertainties within a probabilistic analysis. The development of specific investment recommendations, to improve the reliability prediction, among various potential testing and programmatic options is then accomplished through Bayesian analysis.

Optimized ex-ovo culturing of chick embryos to advanced stages of development.

PubMed

Cloney, Kellie; Franz-Odendaal, Tamara Anne

2015-01-24

Research in anatomy, embryology, and developmental biology has largely relied on the use of model organisms. In order to study development in live embryos model organisms, such as the chicken, are often used. The chicken is an excellent model organism due to its low cost and minimal maintenance, however they present observational challenges because they are enclosed in an opaque eggshell. In order to properly view the embryo as it develops, the shell must be windowed or removed. Both windowing and ex ovo techniques have been developed to assist researchers in the study of embryonic development. However, each of the methods has limitations and challenges. Here, we present a simple, optimized ex ovo culture technique for chicken embryos that enables the observation of embryonic development from stage HH 19 into late stages of development (HH 40), when many organs have developed. This technique is easy to adopt in both undergraduate classes and more advanced research laboratories where embryo manipulations are conducted.

The Arctic Climate Modeling Program: Professional Development for Rural Teachers

ERIC Educational Resources Information Center

Bertram, Kathryn Berry

2010-01-01

The Arctic Climate Modeling Program (ACMP) offered yearlong science, technology, engineering, and math (STEM) professional development to teachers in rural Alaska. Teacher training focused on introducing youth to workforce technologies used in Arctic research. Due to challenges in making professional development accessible to rural teachers, ACMP…

e-Learning Success Model: An Information Systems Perspective

ERIC Educational Resources Information Center

Lee-Post, Anita

2009-01-01

This paper reports the observations made and experience gained from developing and delivering an online quantitative methods course for Business undergraduates. Inspired by issues and challenges experienced in developing the online course, a model is advanced to address the question of how to guide the design, development, and delivery of…

Identification of usual interstitial pneumonia pattern using RNA-Seq and machine learning: challenges and solutions.

PubMed

Choi, Yoonha; Liu, Tiffany Ting; Pankratz, Daniel G; Colby, Thomas V; Barth, Neil M; Lynch, David A; Walsh, P Sean; Raghu, Ganesh; Kennedy, Giulia C; Huang, Jing

2018-05-09

We developed a classifier using RNA sequencing data that identifies the usual interstitial pneumonia (UIP) pattern for the diagnosis of idiopathic pulmonary fibrosis. We addressed significant challenges, including limited sample size, biological and technical sample heterogeneity, and reagent and assay batch effects. We identified inter- and intra-patient heterogeneity, particularly within the non-UIP group. The models classified UIP on transbronchial biopsy samples with a receiver-operating characteristic area under the curve of ~ 0.9 in cross-validation. Using in silico mixed samples in training, we prospectively defined a decision boundary to optimize specificity at ≥85%. The penalized logistic regression model showed greater reproducibility across technical replicates and was chosen as the final model. The final model showed sensitivity of 70% and specificity of 88% in the test set. We demonstrated that the suggested methodologies appropriately addressed challenges of the sample size, disease heterogeneity and technical batch effects and developed a highly accurate and robust classifier leveraging RNA sequencing for the classification of UIP.

Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease.

PubMed

Toapanta, Franklin R; Bernal, Paula J; Fresnay, Stephanie; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

2015-06-01

A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD-) 5-10 days post-challenge. TD criteria included meeting clinical (oral temperature ≥38°C for ≥12 h) and/or microbiological (S. Typhi bacteremia) endpoints. One of the first lines of defense against pathogens are the cells of the innate immune system (e.g., monocytes, dendritic cells -DCs-). Various changes in circulating monocytes and DCs have been described in the murine S. Typhimurium model; however, whether similar changes are present in humans remains to be explored. To address these questions, a subset of volunteers (5 TD and 3 who did not develop typhoid despite oral challenge -NoTD-) were evaluated for changes in circulating monocytes and DCs. Expression of CD38 and CD40 were upregulated in monocytes and DCs in TD volunteers during the disease days (TD-0h to TD-96h). Moreover, integrin α4β7, a gut homing molecule, was upregulated on monocytes but not DCs. CD21 upregulation was only identified in DCs. These changes were not observed among NoTD volunteers despite the same oral challenge. Moreover, monocytes and DCs from NoTD volunteers showed increased binding to S. Typhi one day after challenge. These monocytes showed phosphorylation of p38MAPK, NFkB and Erk1/2 upon stimulation with S. Typhi-LPS-QDot micelles. In contrast, monocytes from TD volunteers showed only a moderate increase in S. Typhi binding 48 h and 96 h post-TD, and only Erk1/2 phosphorylation. This is the first study to describe different activation and migration profiles, as well as differential signaling patterns, in monocytes and DCs which relate directly to the clinical outcome following oral challenge with wild type S. Typhi.

Instantiating the art of war for effects-based operations

NASA Astrophysics Data System (ADS)

Burns, Carla L.

2002-07-01

Effects-Based Operations (EBO) is a mindset, a philosophy and an approach for planning, executing and assessing military operations for the effects they produce rather than the targets or even objectives they deal with. An EBO approach strives to provide economy of force, dynamic tasking, and reduced collateral damage. The notion of EBO is not new. Military Commanders certainly have desired effects in mind when conducting military operations. However, to date EBO has been an art of war that lacks automated techniques and tools that enable effects-based analysis and assessment. Modeling and simulation is at the heart of this challenge. The Air Force Research Laboratory (AFRL) EBO Program is developing modeling techniques and corresponding tool capabilities that can be brought to bear against the challenges presented by effects-based analysis and assessment. Effects-based course-of-action development, center of gravity/target system analysis, and wargaming capabilities are being developed and integrated to help give Commanders the information decision support required to achieve desired national security objectives. This paper presents an introduction to effects-based operations, discusses the benefits of an EBO approach, and focuses on modeling and analysis for effects-based strategy development. An overview of modeling and simulation challenges for EBO is presented, setting the stage for the detailed technical papers in the subject session.

Challenges and opportunities in developmental integrative physiology☆

PubMed Central

Mueller, C.A.; Eme, J.; Burggren, W.W.; Roghair, R.D.; Rundle, S.D.

2015-01-01

This review explores challenges and opportunities in developmental physiology outlined by a symposium at the 2014 American Physiological Society Intersociety Meeting: Comparative Approaches to Grand Challenges in Physiology. Across animal taxa, adverse embryonic/fetal environmental conditions can alter morphological and physiological phenotypes in juveniles or adults, and capacities for developmental plasticity are common phenomena. Human neonates with body sizes at the extremes of perinatal growth are at an increased risk of adult disease, particularly hypertension and cardiovascular disease. There are many rewarding areas of current and future research in comparative developmental physiology. We present key mechanisms, models, and experimental designs that can be used across taxa to investigate patterns in, and implications of, the development of animal phenotypes. Intraspecific variation in the timing of developmental events can be increased through developmental plasticity (heterokairy), and could provide the raw material for selection to produce heterochrony — an evolutionary change in the timing of developmental events. Epigenetics and critical windows research recognizes that in ovo or fetal development represent a vulnerable period in the life history of an animal, when the developing organism may be unable to actively mitigate environmental perturbations. ‘Critical windows’ are periods of susceptibility or vulnerability to environmental or maternal challenges, periods when recovery from challenge is possible, and periods when the phenotype or epigenome has been altered. Developmental plasticity may allow survival in an altered environment, but it also has possible long-term consequences for the animal. “Catch-up growth” in humans after the critical perinatal window has closed elicits adult obesity and exacerbates a programmed hypertensive phenotype (one of many examples of “fetal programing”). Grand challenges for developmental physiology include integrating variation in developmental timing within and across generations, applying multiple stressor dosages and stressor exposure at different developmental timepoints, assessment of epigenetic and parental influences, developing new animal models and techniques, and assessing and implementing these designs and models in human health and development. PMID:25711780

Overuse Injury Assessment Model

DTIC Science & Technology

2007-08-01

and reduce injuries is a continual challenge. Military researchers face challenges to develop better equipment, improve training regimens, and...performed and calculate biomechanical metrics for each activity. Hardware Challenges • Sampling the sensors sufficiently fast • Having adequate bandwidth...second is that the injury rate increases rapidly initially and, third, that the injury rate continues to climb as the cumulative distance increases

Challenges in Materials Transformation Modeling for Polyolefins Industry

NASA Astrophysics Data System (ADS)

Lai, Shih-Yaw; Swogger, Kurt W.

2004-06-01

Unlike most published polymer processing and/or forming research, the transformation of polyolefins to fabricated articles often involves non-confined flow or so-called free surface flow (e.g. fiber spinning, blown films, and cast films) in which elongational flow takes place during a fabrication process. Obviously, the characterization and validation of extensional rheological parameters and their use to develop rheological constitutive models are the focus of polyolefins materials transformation research. Unfortunately, there are challenges that remain with limited validation for non-linear, non-isothermal constitutive models for polyolefins. Further complexity arises in the transformation of polyolefins in the elongational flow system as it involves stress-induced crystallization process. The complicated nature of elongational, non-linear rheology and non-isothermal crystallization kinetics make the development of numerical methods very challenging for the polyolefins materials forming modeling. From the product based company standpoint, the challenges of materials transformation research go beyond elongational rheology, crystallization kinetics and its numerical modeling. In order to make models useful for the polyolefin industry, it is critical to develop links between molecular parameters to both equipment and materials forming parameters. The recent advances in the constrained geometry catalysis and materials sciences understanding (INSITE technology and molecular design capability) has made industrial polyolefinic materials forming modeling more viable due to the fact that the molecular structure of the polymer can be well predicted and controlled during the polymerization. In this paper, we will discuss inter-relationship (models) among molecular parameters such as polymer molecular weight (Mw), molecular weight distribution (MWD), long chain branching (LCB), short chain branching (SCB or comonomer types and distribution) and their affects on shear and elongational rheologies, on tie-molecules probabilities, on non-isothermal stress-induced crystallization, on crystalline/amorphous orientation vs. mechanical property relationship, etc. All of the above mentioned inter-relationships (models) are critical to the successful development of a knowledge based industrial model. Dow Polyolefins and Elastomers business is one of the world largest polyolefins resin producers with the most advanced INSITE technology and a "6-Day model" molecular design capability. Dow also offers one of the broadest polyolefinic product ranges and applications to the market.

Addressing recent docking challenges: A hybrid strategy to integrate template-based and free protein-protein docking.

PubMed

Yan, Yumeng; Wen, Zeyu; Wang, Xinxiang; Huang, Sheng-You

2017-03-01

Protein-protein docking is an important computational tool for predicting protein-protein interactions. With the rapid development of proteomics projects, more and more experimental binding information ranging from mutagenesis data to three-dimensional structures of protein complexes are becoming available. Therefore, how to appropriately incorporate the biological information into traditional ab initio docking has been an important issue and challenge in the field of protein-protein docking. To address these challenges, we have developed a Hybrid DOCKing protocol of template-based and template-free approaches, referred to as HDOCK. The basic procedure of HDOCK is to model the structures of individual components based on the template complex by a template-based method if a template is available; otherwise, the component structures will be modeled based on monomer proteins by regular homology modeling. Then, the complex structure of the component models is predicted by traditional protein-protein docking. With the HDOCK protocol, we have participated in the CPARI experiment for rounds 28-35. Out of the 25 CASP-CAPRI targets for oligomer modeling, our HDOCK protocol predicted correct models for 16 targets, ranking one of the top algorithms in this challenge. Our docking method also made correct predictions on other CAPRI challenges such as protein-peptide binding for 6 out of 8 targets and water predictions for 2 out of 2 targets. The advantage of our hybrid docking approach over pure template-based docking was further confirmed by a comparative evaluation on 20 CASP-CAPRI targets. Proteins 2017; 85:497-512. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Flood Forecasting in Wales: Challenges and Solutions

NASA Astrophysics Data System (ADS)

How, Andrew; Williams, Christopher

2015-04-01

With steep, fast-responding river catchments, exposed coastal reaches with large tidal ranges and large population densities in some of the most at-risk areas; flood forecasting in Wales presents many varied challenges. Utilising advances in computing power and learning from best practice within the United Kingdom and abroad have seen significant improvements in recent years - however, many challenges still remain. Developments in computing and increased processing power comes with a significant price tag; greater numbers of data sources and ensemble feeds brings a better understanding of uncertainty but the wealth of data needs careful management to ensure a clear message of risk is disseminated; new modelling techniques utilise better and faster computation, but lack the history of record and experience gained from the continued use of more established forecasting models. As a flood forecasting team we work to develop coastal and fluvial forecasting models, set them up for operational use and manage the duty role that runs the models in real time. An overview of our current operational flood forecasting system will be presented, along with a discussion on some of the solutions we have in place to address the challenges we face. These include: • real-time updating of fluvial models • rainfall forecasting verification • ensemble forecast data • longer range forecast data • contingency models • offshore to nearshore wave transformation • calculation of wave overtopping

Experimental models in vaccine research: malaria and leishmaniasis

PubMed Central

Teixeira, C.; Gomes, R.

2013-01-01

Animal models have a long history of being useful tools, not only to test and select vaccines, but also to help understand the elaborate details of the immune response that follows infection. Different models have been extensively used to investigate putative immunological correlates of protection against parasitic diseases that are important to reach a successful vaccine. The greatest challenge has been the improvement and adaptation of these models to reflect the reality of human disease and the screening of vaccine candidates capable of overcoming the challenge of natural transmission. This review will discuss the advantages and challenges of using experimental animal models for vaccine development and how the knowledge achieved can be extrapolated to human disease by looking into two important parasitic diseases: malaria and leishmaniasis. PMID:23369975

Decision-Making in Agent-Based Models of Migration: State of the Art and Challenges.

PubMed

Klabunde, Anna; Willekens, Frans

We review agent-based models (ABM) of human migration with respect to their decision-making rules. The most prominent behavioural theories used as decision rules are the random utility theory, as implemented in the discrete choice model, and the theory of planned behaviour. We identify the critical choices that must be made in developing an ABM, namely the modelling of decision processes and social networks. We also discuss two challenges that hamper the widespread use of ABM in the study of migration and, more broadly, demography and the social sciences: (a) the choice and the operationalisation of a behavioural theory (decision-making and social interaction) and (b) the selection of empirical evidence to validate the model. We offer advice on how these challenges might be overcome.

A gene network model accounting for development and evolution of mammalian teeth

PubMed Central

Salazar-Ciudad, Isaac; Jernvall, Jukka

2002-01-01

Generation of morphological diversity remains a challenge for evolutionary biologists because it is unclear how an ultimately finite number of genes involved in initial pattern formation integrates with morphogenesis. Ideally, models used to search for the simplest developmental principles on how genes produce form should account for both developmental process and evolutionary change. Here we present a model reproducing the morphology of mammalian teeth by integrating experimental data on gene interactions and growth into a morphodynamic mechanism in which developing morphology has a causal role in patterning. The model predicts the course of tooth-shape development in different mammalian species and also reproduces key transitions in evolution. Furthermore, we reproduce the known expression patterns of several genes involved in tooth development and their dynamics over developmental time. Large morphological effects frequently can be achieved by small changes, according to this model, and similar morphologies can be produced by different changes. This finding may be consistent with why predicting the morphological outcomes of molecular experiments is challenging. Nevertheless, models incorporating morphology and gene activity show promise for linking genotypes to phenotypes. PMID:12048258

What Do Students Think about Group Work in Business Education? An Investigation into the Benefits, Challenges, and Student-Suggested Solutions

ERIC Educational Resources Information Center

Lee, Seung Hwan Mark; Smith, Donna; Sergueeva, Ksenia

2016-01-01

The authors sought to gain insight on how students view group learning and development as part of their business education experience. Specifically, the authors categorize benefits and challenges using S. A. Wheelan's (2005) integrated model of group development. Additionally, they investigate (from the students' perspective) best practices that…

Specification of the Surface Charging Environment with SHIELDS

NASA Astrophysics Data System (ADS)

Jordanova, V.; Delzanno, G. L.; Henderson, M. G.; Godinez, H. C.; Jeffery, C. A.; Lawrence, E. C.; Meierbachtol, C.; Moulton, J. D.; Vernon, L.; Woodroffe, J. R.; Brito, T.; Toth, G.; Welling, D. T.; Yu, Y.; Albert, J.; Birn, J.; Borovsky, J.; Denton, M.; Horne, R. B.; Lemon, C.; Markidis, S.; Thomsen, M. F.; Young, S. L.

2016-12-01

Predicting variations in the near-Earth space environment that can lead to spacecraft damage and failure, i.e. "space weather", remains a big space physics challenge. A recently funded project through the Los Alamos National Laboratory (LANL) Directed Research and Development (LDRD) program aims at developing a new capability to understand, model, and predict Space Hazards Induced near Earth by Large Dynamic Storms, the SHIELDS framework. The project goals are to understand the dynamics of the surface charging environment (SCE), the hot (keV) electrons representing the source and seed populations for the radiation belts, on both macro- and microscale. Important physics questions related to rapid particle injection and acceleration associated with magnetospheric storms and substorms as well as plasma waves are investigated. These challenging problems are addressed using a team of world-class experts in the fields of space science and computational plasma physics, and state-of-the-art models and computational facilities. In addition to physics-based models (like RAM-SCB, BATS-R-US, and iPIC3D), new data assimilation techniques employing data from LANL instruments on the Van Allen Probes and geosynchronous satellites are developed. Simulations with the SHIELDS framework of the near-Earth space environment where operational satellites reside are presented. Further model development and the organization of a "Spacecraft Charging Environment Challenge" by the SHIELDS project at LANL in collaboration with the NSF Geospace Environment Modeling (GEM) Workshop and the multi-agency Community Coordinated Modeling Center (CCMC) to assess the accuracy of SCE predictions are discussed.

Light-weight Parallel Python Tools for Earth System Modeling Workflows

NASA Astrophysics Data System (ADS)

Mickelson, S. A.; Paul, K.; Xu, H.; Dennis, J.; Brown, D. I.

2015-12-01

With the growth in computing power over the last 30 years, earth system modeling codes have become increasingly data-intensive. As an example, it is expected that the data required for the next Intergovernmental Panel on Climate Change (IPCC) Assessment Report (AR6) will increase by more than 10x to an expected 25PB per climate model. Faced with this daunting challenge, developers of the Community Earth System Model (CESM) have chosen to change the format of their data for long-term storage from time-slice to time-series, in order to reduce the required download bandwidth needed for later analysis and post-processing by climate scientists. Hence, efficient tools are required to (1) perform the transformation of the data from time-slice to time-series format and to (2) compute climatology statistics, needed for many diagnostic computations, on the resulting time-series data. To address the first of these two challenges, we have developed a parallel Python tool for converting time-slice model output to time-series format. To address the second of these challenges, we have developed a parallel Python tool to perform fast time-averaging of time-series data. These tools are designed to be light-weight, be easy to install, have very few dependencies, and can be easily inserted into the Earth system modeling workflow with negligible disruption. In this work, we present the motivation, approach, and testing results of these two light-weight parallel Python tools, as well as our plans for future research and development.

Challenges in Understanding and Development of Predictive Models of Plasma Assisted Combustion

DTIC Science & Technology

2014-01-01

and electron temperature in transient plasmas sustained by nanosecond pulse duration discharges, and their comparison with modeling predictions, are...in nanosecond pulse discharge in nitrogen at 0.25 bar, using the kinetic model developed in Ref. [11]. Rapid electric field reduction during...discharge pulses with kinetic modeling calculations, using conventional hydrocarbon-air combustion mechanisms. Although modeling predictions for H2-air

Controlled human infection models for vaccine development: Zika virus debate.

PubMed

Gopichandran, Vijayaprasad

2018-01-01

An ethics panel, convened by the National Institute of Health and other research bodies in the USA, disallowed researchers from the Johns Hopkins University and University of Vermont from performing controlled human infection of healthy volunteers to develop a vaccine against Zika virus infection. The members published their ethical analysis and recommendations in February 2017. They have elaborated on the risks posed by human challenge with Zika virus to the volunteers and other uninvolved third parties and have systematically analysed the social value of such a human challenge experiment. They have also posited some mandatory ethical requirements which should be met before allowing the infection of healthy volunteers with the Zika virus. This commentary elaborates on the debate on the ethics of the human challenge model for the development of a Zika virus vaccine and the role of systematic ethical analysis in protecting the interests of research participants. It further analyses the importance of this debate to the development of a Zika vaccine in India.

Literacy at Work: The Workplace Basic Education Project Model of Delivery. EAE646 Language and Literacies: Contexts and Challenges in the Workplace.

ERIC Educational Resources Information Center

Newcombe, Jude

This publication is part of the study materials for the distance education course, Language and Literacies: Contexts and Challenges in the Workplace, in the Open Campus Program at Deakin University. The document traces the historical development of Australia's Workplace Basic Education Project (WBEP) model for taking literacy provision into the…

Challenges in the development of chronic pulmonary hypertension models in large animals

PubMed Central

Rothman, Abraham; Wiencek, Robert G.; Davidson, Stephanie; Evans, William N.; Restrepo, Humberto; Sarukhanov, Valeri; Mann, David

2017-01-01

Pulmonary hypertension (PH) results in significant morbidity and mortality. Chronic PH animal models may advance the study of PH’s mechanisms, evolution, and therapy. In this report, we describe the challenges and successes in developing three models of chronic PH in large animals: two models (one canine and one swine) utilized repeated infusions of ceramic microspheres into the pulmonary vascular bed, and the third model employed a surgical aorto-pulmonary shunt. In the canine model, seven dogs underwent microsphere infusions that resulted in progressive elevation of pulmonary arterial pressure over a few months. In this model, pulmonary endoarterial tissue was obtained for histology. In the aorto-pulmonary shunt swine model, 17 pigs developed systemic level pulmonary pressures after 2–3 months. In this model, pulmonary endoarterial tissue was sequentially obtained to assess for changes in gene and microRNA expression. In the swine microsphere infusion model, three pigs developed only a modest chronic increase in pulmonary arterial pressure, despite repeated infusions of microspheres (up to 40 in one animal). The main purpose of this model was for vasodilator testing, which was performed successfully immediately after acute microsphere infusions. Chronic PH in large animal models can be successfully created; however, a model’s characteristics need to match the investigational goals. PMID:28680575

Model Uncertainty Quantification Methods In Data Assimilation

NASA Astrophysics Data System (ADS)

Pathiraja, S. D.; Marshall, L. A.; Sharma, A.; Moradkhani, H.

2017-12-01

Data Assimilation involves utilising observations to improve model predictions in a seamless and statistically optimal fashion. Its applications are wide-ranging; from improving weather forecasts to tracking targets such as in the Apollo 11 mission. The use of Data Assimilation methods in high dimensional complex geophysical systems is an active area of research, where there exists many opportunities to enhance existing methodologies. One of the central challenges is in model uncertainty quantification; the outcome of any Data Assimilation study is strongly dependent on the uncertainties assigned to both observations and models. I focus on developing improved model uncertainty quantification methods that are applicable to challenging real world scenarios. These include developing methods for cases where the system states are only partially observed, where there is little prior knowledge of the model errors, and where the model error statistics are likely to be highly non-Gaussian.

Prospectus: towards the development of high-fidelity models of wall turbulence at large Reynolds number

NASA Astrophysics Data System (ADS)

Klewicki, J. C.; Chini, G. P.; Gibson, J. F.

2017-03-01

Recent and on-going advances in mathematical methods and analysis techniques, coupled with the experimental and computational capacity to capture detailed flow structure at increasingly large Reynolds numbers, afford an unprecedented opportunity to develop realistic models of high Reynolds number turbulent wall-flow dynamics. A distinctive attribute of this new generation of models is their grounding in the Navier-Stokes equations. By adhering to this challenging constraint, high-fidelity models ultimately can be developed that not only predict flow properties at high Reynolds numbers, but that possess a mathematical structure that faithfully captures the underlying flow physics. These first-principles models are needed, for example, to reliably manipulate flow behaviours at extreme Reynolds numbers. This theme issue of Philosophical Transactions of the Royal Society A provides a selection of contributions from the community of researchers who are working towards the development of such models. Broadly speaking, the research topics represented herein report on dynamical structure, mechanisms and transport; scale interactions and self-similarity; model reductions that restrict nonlinear interactions; and modern asymptotic theories. In this prospectus, the challenges associated with modelling turbulent wall-flows at large Reynolds numbers are briefly outlined, and the connections between the contributing papers are highlighted.

A Group Counseling Model for Developing Manhood among Black Male Adolescents.

ERIC Educational Resources Information Center

Lee, Courtland

1991-01-01

A dialogue is presented, which highlights the meaning of success as a Black man. C. Lee's Black Manhood Training Model is discussed, which was developed as a group counseling experience in a school setting for 13- to 17-year-old Black boys to address the challenges of Black male development. (SLD)

Development challenges of secondary and small airports in California [research brief].

DOT National Transportation Integrated Search

2012-06-01

This report investigates the challenges facing secondary and small airports in California. Low-cost carriers (LCC) have slowly risen to become the dominant air service providers in the state. Their dominance and their unique business model have signi...

Technology Transfer Challenges for High-Assurance Software Engineering Tools

NASA Technical Reports Server (NTRS)

Koga, Dennis (Technical Monitor); Penix, John; Markosian, Lawrence Z.

2003-01-01

In this paper, we describe our experience with the challenges thar we are currently facing in our effort to develop advanced software verification and validation tools. We categorize these challenges into several areas: cost benefits modeling, tool usability, customer application domain, and organizational issues. We provide examples of challenges in each area and identrfj, open research issues in areas which limit our ability to transfer high-assurance software engineering tools into practice.

Rotary-Wing Relevant Compressor Aero Research and Technology Development Activities at Glenn Research Center

NASA Technical Reports Server (NTRS)

Welch, Gerard E.; Hathaway, Michael D.; Skoch, Gary J.; Snyder, Christopher A.

2012-01-01

Technical challenges of compressors for future rotorcraft engines are driven by engine-level and component-level requirements. Cycle analyses are used to highlight the engine-level challenges for 3000, 7500, and 12000 SHP-class engines, which include retention of performance and stability margin at low corrected flows, and matching compressor type, axial-flow or centrifugal, to the low corrected flows and high temperatures in the aft stages. At the component level: power-to-weight and efficiency requirements impel designs with lower inherent aerodynamic stability margin; and, optimum engine overall pressure ratios lead to small blade heights and the associated challenges of scale, particularly increased clearance-to-span ratios. The technical challenges associated with the aerodynamics of low corrected flows and stability management impel the compressor aero research and development efforts reviewed herein. These activities include development of simple models for clearance sensitivities to improve cycle calculations, full-annulus, unsteady Navier-Stokes simulations used to elucidate stall, its inception, and the physics of stall control by discrete tip-injection, development of an actuator-duct-based model for rapid simulation of nonaxisymmetric flow fields (e.g., due inlet circumferential distortion), advanced centrifugal compressor stage development and experimentation, and application of stall control in a T700 engine.

Building a Course on Global Sustainability using the grand challenges of Energy-Water-Climate

NASA Astrophysics Data System (ADS)

Myers, J. D.

2012-12-01

GEOL1600: Global Sustainability: Managing the Earth's Resources is a lower division integrated science course at the University of Wyoming that fulfills the university's science requirement. Course content and context has been developed using the grand challenge nexus of energy-water-and climate (EWC). The interconnection of these issues, their social relevance and timeliness has provided a framework that gives students an opportunity to recognize why STEM is relevant to their lives regardless of their ultimate professional career choices. The EWC nexus provides the filter to sieve the course's STEM content. It also provides an ideal mechanism by which the non-STEM perspectives important in grand challenge solutions can be seamlessly incorporated in the course. Through a combination of content and context, the relevance of these issues engage students in their own learning. Development of the course followed the Grand Challenge Scientific Literacy (GCSL) model independently developed by the author and two colleagues at the University of Wyoming. This course model stresses science principles centered on the nature of science (e.g., fundamental premises, habits of mind, critical thinking) and unifying scientific concepts (e.g., methods and tools, experimentation, modeling). Grand challenge principles identify the STEM and non-STEM concepts needed to understand the grand challenges, drawing on multiple STEM and non-STEM disciplines and subjects (i.e., economics, politics, unintended consequences, roles of stakeholders). Using the EWC nexus filter and building on the Grand Challenge Principles, specific content included in the course is selected is that most relevant to understanding the Grand Challenges, thereby stressing content depth over breadth. Because quantitative data and reasoning is critical to effectively evaluating challenge solutions, QR is a component of nearly all class activities, while engineering and technology aspects of grand challenges are explicitly stressed. Running concurrently through the course is a consideration of personal perspectives and their influence on student learning, particularly for controversial subjects. Organizationally, the course consists of three one hour lectures and a two hour lab each week. The lectures are used to introduce content and prepare the knowledge base students need for lab. Complementing traditional lectures are lecture worksheets (short activities applying topics previously presented in lecture) and lecture activities (more involved exercises that present a problem the students need to solve using previously learned scientific content and QR skills and tools). Labs focus on case studies set in global social contexts that are timely and relevant. Labs stress scientific skills (modeling groundwater flow) and also consider political and environmental issues, e.g. developing a policy to manage SO2 emissions from copper smelting. The ideas, concepts, educational materials and content developed in this course have been used as the basis for two Math Science Partnerships that have provided professional development for middle and high school science and math teachers and K-12 social, math and science teachers. These programs have worked with teachers to break down the barriers between disciplines and foster collaborative learning centered on socially relevant grand challenges.

The legal and ethical concerns that arise from using complex predictive analytics in health care.

PubMed

Cohen, I Glenn; Amarasingham, Ruben; Shah, Anand; Xie, Bin; Lo, Bernard

2014-07-01

Predictive analytics, or the use of electronic algorithms to forecast future events in real time, makes it possible to harness the power of big data to improve the health of patients and lower the cost of health care. However, this opportunity raises policy, ethical, and legal challenges. In this article we analyze the major challenges to implementing predictive analytics in health care settings and make broad recommendations for overcoming challenges raised in the four phases of the life cycle of a predictive analytics model: acquiring data to build the model, building and validating it, testing it in real-world settings, and disseminating and using it more broadly. For instance, we recommend that model developers implement governance structures that include patients and other stakeholders starting in the earliest phases of development. In addition, developers should be allowed to use already collected patient data without explicit consent, provided that they comply with federal regulations regarding research on human subjects and the privacy of health information. Project HOPE—The People-to-People Health Foundation, Inc.

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

J. Carmack; L. Braase; F. Goldner

The mission of the Advanced Fuels Campaign (AFC) is to perform Research, Development, and Demonstration (RD&D) activities for advanced fuel forms (including cladding) to enhance the performance and safety of the nation’s current and future reactors, enhance proliferation resistance of nuclear fuel, effectively utilize nuclear energy resources, and address the longer-term waste management challenges. This includes development of a state of the art Research and Development (R&D) infrastructure to support the use of a “goal oriented science based approach.” AFC uses a “goal oriented, science based approach” aimed at a fundamental understanding of fuel and cladding fabrication methods and performancemore » under irradiation, enabling the pursuit of multiple fuel forms for future fuel cycle options. This approach includes fundamental experiments, theory, and advanced modeling and simulation. One of the most challenging aspects of AFC is the management, integration, and coordination of major R&D activities across multiple organizations. AFC interfaces and collaborates with Fuel Cycle Technologies (FCT) campaigns, universities, industry, various DOE programs and laboratories, federal agencies (e.g., Nuclear Regulatory Commission [NRC]), and international organizations. Key challenges are the development of fuel technologies to enable major increases in fuel performance (safety, reliability, power and burnup) beyond current technologies, and development of characterization methods and predictive fuel performance models to enable more efficient development and licensing of advanced fuels. Challenged with the research and development of fuels for two different reactor technology platforms, AFC targeted transmutation fuel development and focused ceramic fuel development for Advanced LWR Fuels.« less

Demand-Side Job Development and System Change.

ERIC Educational Resources Information Center

Gilbride, Dennis; Stensrud, Robert

1999-01-01

Authors discuss demand-side job development as a model for improving and providing rehabilitation services to consumers and employers. It stresses quality employment outcomes, consumer choice and empowerment, and a productive partnership between consumer and counselor. Delineates systemic challenges this model poses to traditional vocational…

Software Systems for High-performance Quantum Computing

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

Humble, Travis S; Britt, Keith A

Quantum computing promises new opportunities for solving hard computational problems, but harnessing this novelty requires breakthrough concepts in the design, operation, and application of computing systems. We define some of the challenges facing the development of quantum computing systems as well as software-based approaches that can be used to overcome these challenges. Following a brief overview of the state of the art, we present models for the quantum programming and execution models, the development of architectures for hybrid high-performance computing systems, and the realization of software stacks for quantum networking. This leads to a discussion of the role that conventionalmore » computing plays in the quantum paradigm and how some of the current challenges for exascale computing overlap with those facing quantum computing.« less

State of the industry for drug-diagnostic development: challenge and change on the path to precision medicine.

PubMed

Milne, Christopher-Paul; Cohen, Joshua; Chakravarthy, Ranjana; Awatin, Josephine

2016-07-01

Four challenges to the adoption of personalized medicine were identified in the mid-2000s - adherence to the blockbuster model, the lack of a supportive regulatory environment, the dysfunctional payment system and physician barriers. In this article, we report on our study findings based on interviews with 24 senior executives from leading drug and diagnostics companies to assess progress made in addressing those challenges over the last decade. Overall, we found that even with payer pushback and adjusting to new business models, the majority of developers expected their business to increase over the next 5 years. Several factors that unexpectedly helped to shape the personalized medicine landscape, such as the growth of support in genomic medicine from the public sector, are also discussed.

Drugs for Neglected Diseases initiative model of drug development for neglected diseases: current status and future challenges.

PubMed

Ioset, Jean-Robert; Chang, Shing

2011-09-01

The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven organization committed to the development of new treatments for neglected diseases. Created in 2003, DNDi has delivered four improved treatments for malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is to build a solid R&D portfolio for neglected diseases and to deliver preclinical candidates in a timely manner using an original model based on partnership. To address this challenge DNDi has remodeled its discovery activities from a project-based academic-bound network to a fully integrated process-oriented platform in close collaboration with pharmaceutical companies. This discovery platform relies on dedicated screening capacity and lead-optimization consortia supported by a pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

Discrete-continuum multiscale model for transport, biomass development and solid restructuring in porous media

NASA Astrophysics Data System (ADS)

Ray, Nadja; Rupp, Andreas; Prechtel, Alexander

2017-09-01

Upscaling transport in porous media including both biomass development and simultaneous structural changes in the solid matrix is extremely challenging. This is because both affect the medium's porosity as well as mass transport parameters and flow paths. We address this challenge by means of a multiscale model. At the pore scale, the local discontinuous Galerkin (LDG) method is used to solve differential equations describing particularly the bacteria's and the nutrient's development. Likewise, a sticky agent tightening together solid or bio cells is considered. This is combined with a cellular automaton method (CAM) capturing structural changes of the underlying computational domain stemming from biomass development and solid restructuring. Findings from standard homogenization theory are applied to determine the medium's characteristic time- and space-dependent properties. Investigating these results enhances our understanding of the strong interplay between a medium's functional properties and its geometric structure. Finally, integrating such properties as model parameters into models defined on a larger scale enables reflecting the impact of pore scale processes on the larger scale.

Flea-borne transmission model to evaluate vaccine efficacy against naturally acquired bubonic plague.

PubMed

Jarrett, Clayton O; Sebbane, Florent; Adamovicz, Jeffrey J; Andrews, Gerard P; Hinnebusch, B Joseph

2004-04-01

A flea-to-mouse transmission model was developed for use in testing new candidate vaccines for the ability to protect against flea-borne plague. The model was used to evaluate a recombinant fusion protein vaccine consisting of the Yersinia pestis F1 and V antigens. After one to three challenges with Y. pestis-infected fleas, 14 of 15 unvaccinated control mice developed plague, with an average septicemia level of 9.2 x 10(8) Y. pestis CFU/ml. None of 15 vaccinated mice developed the disease after similar challenges, and serological testing indicated that transmitted bacteria were eliminated by the immune system before extensive replication and systemic infection could occur. The transmission and development of disease in control mice correlated with the number of bites by blocked fleas but not with the total number of fleabites. The model provides a means to directly assess the efficacy of new vaccines to prevent naturally acquired bubonic plague and to study events at the vector-host interface that lead to dissemination and disease.

Designing blended learning interventions for the 21st century student.

PubMed

Eagleton, Saramarie

2017-06-01

The learning requirements of diverse groups of students in higher education challenge educators to design learning interventions that meet the need of 21st century students. A model was developed to assist lecturers, especially those that are new to the profession, to use a blended approach to design meaningful learning interventions for physiology. The aim of the model is to encourage methodical development of learning interventions, while the purpose is to provide conceptual and communication tools that can be used to develop appropriate operational learning interventions. A whole brain approach that encourages challenging the four quadrants is encouraged. The main arguments of the model are to first determine the learning task requirements, as these will inform the design and development of learning interventions to facilitate learning and the assessment thereof. Delivery of the content is based on a blended approach. Copyright © 2017 the American Physiological Society.

The mathematics of cancer: integrating quantitative models.

PubMed

Altrock, Philipp M; Liu, Lin L; Michor, Franziska

2015-12-01

Mathematical modelling approaches have become increasingly abundant in cancer research. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments. In turn, mathematical modelling contributes to cancer research by helping to elucidate mechanisms and by providing quantitative predictions that can be validated. The recent expansion of quantitative models addresses many questions regarding tumour initiation, progression and metastases as well as intra-tumour heterogeneity, treatment responses and resistance. Mathematical models can complement experimental and clinical studies, but also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research in cancer biology.

Vehicle Lightweighting: Challenges and Opportunities with Aluminum

NASA Astrophysics Data System (ADS)

Sachdev, Anil K.; Mishra, Raja K.; Mahato, Anirban; Alpas, Ahmet

Rising energy costs, consumer preferences and regulations drive requirements for fuel economy, performance, comfort, safety and cost of future automobiles. These conflicting situations offer challenges for vehicle lightweighting, for which aluminum applications are key. This paper describes product design needs and materials and process development opportunities driven by theoretical, experimental and modeling tools in the area of sheet and castings. Computational tools and novel experimental techniques used in their development are described. The paper concludes with challenges that lie ahead for pervasive use of aluminum and the necessary fundamental R&D that is still needed.

Advantages and Challenges of Using Physics Curricula as a Model for Reforming an Undergraduate Biology Course

ERIC Educational Resources Information Center

Donovan, D. A.; Atkins, L. J.; Salter, I. Y.; Gallagher, D. J.; Kratz, R. F.; Rousseau, J. V.; Nelson, G. D.

2013-01-01

We report on the development of a life sciences curriculum, targeted to undergraduate students, which was modeled after a commercially available physics curriculum and based on aspects of how people learn. Our paper describes the collaborative development process and necessary modifications required to apply a physics pedagogical model in a life…

Predicting the Risk of Attrition for Undergraduate Students with Time Based Modelling

ERIC Educational Resources Information Center

Chai, Kevin E. K.; Gibson, David

2015-01-01

Improving student retention is an important and challenging problem for universities. This paper reports on the development of a student attrition model for predicting which first year students are most at-risk of leaving at various points in time during their first semester of study. The objective of developing such a model is to assist…

Challenges and opportunities for improved understanding of regional climate dynamics

NASA Astrophysics Data System (ADS)

Collins, Matthew; Minobe, Shoshiro; Barreiro, Marcelo; Bordoni, Simona; Kaspi, Yohai; Kuwano-Yoshida, Akira; Keenlyside, Noel; Manzini, Elisa; O'Reilly, Christopher H.; Sutton, Rowan; Xie, Shang-Ping; Zolina, Olga

2018-01-01

Dynamical processes in the atmosphere and ocean are central to determining the large-scale drivers of regional climate change, yet their predictive understanding is poor. Here, we identify three frontline challenges in climate dynamics where significant progress can be made to inform adaptation: response of storms, blocks and jet streams to external forcing; basin-to-basin and tropical-extratropical teleconnections; and the development of non-linear predictive theory. We highlight opportunities and techniques for making immediate progress in these areas, which critically involve the development of high-resolution coupled model simulations, partial coupling or pacemaker experiments, as well as the development and use of dynamical metrics and exploitation of hierarchies of models.

Development of Systems Engineering Maturity Models and Management Tools

DTIC Science & Technology

2011-01-21

Ph.D., Senior Personnel, Stevens Institute of Technology Abhi Deshmukh, Ph.D., Senior Personnel, Texas A&M University Matin Sarfaraz, Research ...WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Stevens Institute of Technology,Systems Engineering Research Center (SERC),1...tools (MPT) for effectively and efficiently addressing these challenges are likewise being challenged. The goal of this research was to develop a

Computational Psychiatry and the Challenge of Schizophrenia.

PubMed

Krystal, John H; Murray, John D; Chekroud, Adam M; Corlett, Philip R; Yang, Genevieve; Wang, Xiao-Jing; Anticevic, Alan

2017-05-01

Schizophrenia research is plagued by enormous challenges in integrating and analyzing large datasets and difficulties developing formal theories related to the etiology, pathophysiology, and treatment of this disorder. Computational psychiatry provides a path to enhance analyses of these large and complex datasets and to promote the development and refinement of formal models for features of this disorder. This presentation introduces the reader to the notion of computational psychiatry and describes discovery-oriented and theory-driven applications to schizophrenia involving machine learning, reinforcement learning theory, and biophysically-informed neural circuit models. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2017.

Challenges to the development of complex virtual reality surgical simulations.

PubMed

Seymour, N E; Røtnes, J S

2006-11-01

Virtual reality simulation in surgical training has become more widely used and intensely investigated in an effort to develop safer, more efficient, measurable training processes. The development of virtual reality simulation of surgical procedures has begun, but well-described technical obstacles must be overcome to permit varied training in a clinically realistic computer-generated environment. These challenges include development of realistic surgical interfaces and physical objects within the computer-generated environment, modeling of realistic interactions between objects, rendering of the surgical field, and development of signal processing for complex events associated with surgery. Of these, the realistic modeling of tissue objects that are fully responsive to surgical manipulations is the most challenging. Threats to early success include relatively limited resources for development and procurement, as well as smaller potential for return on investment than in other simulation industries that face similar problems. Despite these difficulties, steady progress continues to be made in these areas. If executed properly, virtual reality offers inherent advantages over other training systems in creating a realistic surgical environment and facilitating measurement of surgeon performance. Once developed, complex new virtual reality training devices must be validated for their usefulness in formative training and assessment of skill to be established.

Summary of "Using Student Growth to Evaluate Educators of Students with Disabilities: Issues, Challenges, and Next Steps": A Forum of State Special Education and Teacher Effectiveness Experts and Researchers. Forum Summary

ERIC Educational Resources Information Center

Holdheide, Lynn; Browder, Diane; Warren, Sandra; Buzick, Heather; Jones, Nathan

2012-01-01

With the current emphasis in educational policy on improving teacher effectiveness, states and school districts are quickly developing and implementing new models of teacher evaluation. However, few models address the unique challenges in accurately measuring achievement growth of students with disabilities (including those participating in…

Animal models for HIV/AIDS research

PubMed Central

Hatziioannou, Theodora; Evans, David T.

2015-01-01

The AIDS pandemic continues to present us with unique scientific and public health challenges. Although the development of effective antiretroviral therapy has been a major triumph, the emergence of drug resistance requires active management of treatment regimens and the continued development of new antiretroviral drugs. Moreover, despite nearly 30 years of intensive investigation, we still lack the basic scientific knowledge necessary to produce a safe and effective vaccine against HIV-1. Animal models offer obvious advantages in the study of HIV/AIDS, allowing for a more invasive investigation of the disease and for preclinical testing of drugs and vaccines. Advances in humanized mouse models, non-human primate immunogenetics and recombinant challenge viruses have greatly increased the number and sophistication of available mouse and simian models. Understanding the advantages and limitations of each of these models is essential for the design of animal studies to guide the development of vaccines and antiretroviral therapies for the prevention and treatment of HIV-1 infection. PMID:23154262

Pedagogy of the logic model: teaching undergraduates to work together to change their communities.

PubMed

Zimmerman, Lindsey; Kamal, Zohra; Kim, Hannah

2013-01-01

Undergraduate community psychology courses can empower students to address challenging problems in their local communities. Creating a logic model is an experiential way to learn course concepts by "doing." Throughout the semester, students work with peers to define a problem, develop an intervention, and plan an evaluation focused on an issue of concern to them. This report provides an overview of how to organize a community psychology course around the creation of a logic model in order for students to develop this applied skill. Two undergraduate student authors report on their experience with the logic model assignment, describing the community problem they chose to address, what they learned from the assignment, what they found challenging, and what they are doing now in their communities based on what they learned.

Use of computational modeling combined with advanced visualization to develop strategies for the design of crop ideotypes to address food security

DOE PAGES

Christensen, A. J.; Srinivasan, V.; Hart, J. C.; ...

2018-03-17

Sustainable crop production is a contributing factor to current and future food security. Innovative technologies are needed to design strategies that will achieve higher crop yields on less land and with fewer resources. Computational modeling coupled with advanced scientific visualization enables researchers to explore and interact with complex agriculture, nutrition, and climate data to predict how crops will respond to untested environments. These virtual observations and predictions can direct the development of crop ideotypes designed to meet future yield and nutritional demands. This review surveys modeling strategies for the development of crop ideotypes and scientific visualization technologies that have ledmore » to discoveries in “big data” analysis. Combined modeling and visualization approaches have been used to realistically simulate crops and to guide selection that immediately enhances crop quantity and quality under challenging environmental conditions. Lastly, this survey of current and developing technologies indicates that integrative modeling and advanced scientific visualization may help overcome challenges in agriculture and nutrition data as large-scale and multidimensional data become available in these fields.« less

Use of computational modeling combined with advanced visualization to develop strategies for the design of crop ideotypes to address food security

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

Christensen, A. J.; Srinivasan, V.; Hart, J. C.

Sustainable crop production is a contributing factor to current and future food security. Innovative technologies are needed to design strategies that will achieve higher crop yields on less land and with fewer resources. Computational modeling coupled with advanced scientific visualization enables researchers to explore and interact with complex agriculture, nutrition, and climate data to predict how crops will respond to untested environments. These virtual observations and predictions can direct the development of crop ideotypes designed to meet future yield and nutritional demands. This review surveys modeling strategies for the development of crop ideotypes and scientific visualization technologies that have ledmore » to discoveries in “big data” analysis. Combined modeling and visualization approaches have been used to realistically simulate crops and to guide selection that immediately enhances crop quantity and quality under challenging environmental conditions. Lastly, this survey of current and developing technologies indicates that integrative modeling and advanced scientific visualization may help overcome challenges in agriculture and nutrition data as large-scale and multidimensional data become available in these fields.« less

Use of computational modeling combined with advanced visualization to develop strategies for the design of crop ideotypes to address food security.

PubMed

Christensen, A J; Srinivasan, Venkatraman; Hart, John C; Marshall-Colon, Amy

2018-05-01

Sustainable crop production is a contributing factor to current and future food security. Innovative technologies are needed to design strategies that will achieve higher crop yields on less land and with fewer resources. Computational modeling coupled with advanced scientific visualization enables researchers to explore and interact with complex agriculture, nutrition, and climate data to predict how crops will respond to untested environments. These virtual observations and predictions can direct the development of crop ideotypes designed to meet future yield and nutritional demands. This review surveys modeling strategies for the development of crop ideotypes and scientific visualization technologies that have led to discoveries in "big data" analysis. Combined modeling and visualization approaches have been used to realistically simulate crops and to guide selection that immediately enhances crop quantity and quality under challenging environmental conditions. This survey of current and developing technologies indicates that integrative modeling and advanced scientific visualization may help overcome challenges in agriculture and nutrition data as large-scale and multidimensional data become available in these fields.

Use of computational modeling combined with advanced visualization to develop strategies for the design of crop ideotypes to address food security

PubMed Central

Christensen, A J; Srinivasan, Venkatraman; Hart, John C; Marshall-Colon, Amy

2018-01-01

Abstract Sustainable crop production is a contributing factor to current and future food security. Innovative technologies are needed to design strategies that will achieve higher crop yields on less land and with fewer resources. Computational modeling coupled with advanced scientific visualization enables researchers to explore and interact with complex agriculture, nutrition, and climate data to predict how crops will respond to untested environments. These virtual observations and predictions can direct the development of crop ideotypes designed to meet future yield and nutritional demands. This review surveys modeling strategies for the development of crop ideotypes and scientific visualization technologies that have led to discoveries in “big data” analysis. Combined modeling and visualization approaches have been used to realistically simulate crops and to guide selection that immediately enhances crop quantity and quality under challenging environmental conditions. This survey of current and developing technologies indicates that integrative modeling and advanced scientific visualization may help overcome challenges in agriculture and nutrition data as large-scale and multidimensional data become available in these fields. PMID:29562368

Hydrologic modeling for water resource assessment in a developing country: the Rwanda case study

Treesearch

Steve McNulty; Erika Cohen Mack; Ge Sun; Peter Caldwell

2016-01-01

Accurate water resources assessment using hydrologic models can be a challenge anywhere, but particularly for developing countries with limited financial and technical resources. Developing countries could most benefit from the water resource planning capabilities that hydrologic models can provide, but these countries are least likely to have the data needed to run ...

Development of a sustainable community-based dental education program.

PubMed

Piskorowski, Wilhelm A; Fitzgerald, Mark; Mastey, Jerry; Krell, Rachel E

2011-08-01

Increasing the use of community-based programs is an important trend in improving dental education to meet the needs of students and the public. To support this trend, understanding the history of programs that have established successful models for community-based education is valuable for the creation and development of new programs. The community-based education model of the University of Michigan School of Dentistry (UMSOD) offers a useful guide for understanding the essential steps and challenges involved in developing a successful program. Initial steps in program development were as follows: raising funds, selecting an outreach clinical model, and recruiting clinics to become partners. As the program developed, the challenges of creating a sustainable financial model with the highest educational value required the inclusion of new clinical settings and the creation of a unique revenue-sharing model. Since the beginning of the community-based program at UMSOD in 2000, the number of community partners has increased to twenty-seven clinics, and students have treated thousands of patients in need. Fourth-year students now spend a minimum of ten weeks in community-based clinical education. The community-based program at UMSOD demonstrates the value of service-based education and offers a sustainable model for the development of future programs.

Testing Scientific Software: A Systematic Literature Review.

PubMed

Kanewala, Upulee; Bieman, James M

2014-10-01

Scientific software plays an important role in critical decision making, for example making weather predictions based on climate models, and computation of evidence for research publications. Recently, scientists have had to retract publications due to errors caused by software faults. Systematic testing can identify such faults in code. This study aims to identify specific challenges, proposed solutions, and unsolved problems faced when testing scientific software. We conducted a systematic literature survey to identify and analyze relevant literature. We identified 62 studies that provided relevant information about testing scientific software. We found that challenges faced when testing scientific software fall into two main categories: (1) testing challenges that occur due to characteristics of scientific software such as oracle problems and (2) testing challenges that occur due to cultural differences between scientists and the software engineering community such as viewing the code and the model that it implements as inseparable entities. In addition, we identified methods to potentially overcome these challenges and their limitations. Finally we describe unsolved challenges and how software engineering researchers and practitioners can help to overcome them. Scientific software presents special challenges for testing. Specifically, cultural differences between scientist developers and software engineers, along with the characteristics of the scientific software make testing more difficult. Existing techniques such as code clone detection can help to improve the testing process. Software engineers should consider special challenges posed by scientific software such as oracle problems when developing testing techniques.

solveME: fast and reliable solution of nonlinear ME models.

PubMed

Yang, Laurence; Ma, Ding; Ebrahim, Ali; Lloyd, Colton J; Saunders, Michael A; Palsson, Bernhard O

2016-09-22

Genome-scale models of metabolism and macromolecular expression (ME) significantly expand the scope and predictive capabilities of constraint-based modeling. ME models present considerable computational challenges: they are much (>30 times) larger than corresponding metabolic reconstructions (M models), are multiscale, and growth maximization is a nonlinear programming (NLP) problem, mainly due to macromolecule dilution constraints. Here, we address these computational challenges. We develop a fast and numerically reliable solution method for growth maximization in ME models using a quad-precision NLP solver (Quad MINOS). Our method was up to 45 % faster than binary search for six significant digits in growth rate. We also develop a fast, quad-precision flux variability analysis that is accelerated (up to 60× speedup) via solver warm-starts. Finally, we employ the tools developed to investigate growth-coupled succinate overproduction, accounting for proteome constraints. Just as genome-scale metabolic reconstructions have become an invaluable tool for computational and systems biologists, we anticipate that these fast and numerically reliable ME solution methods will accelerate the wide-spread adoption of ME models for researchers in these fields.

Computational Social Creativity.

PubMed

Saunders, Rob; Bown, Oliver

2015-01-01

This article reviews the development of computational models of creativity where social interactions are central. We refer to this area as computational social creativity. Its context is described, including the broader study of creativity, the computational modeling of other social phenomena, and computational models of individual creativity. Computational modeling has been applied to a number of areas of social creativity and has the potential to contribute to our understanding of creativity. A number of requirements for computational models of social creativity are common in artificial life and computational social science simulations. Three key themes are identified: (1) computational social creativity research has a critical role to play in understanding creativity as a social phenomenon and advancing computational creativity by making clear epistemological contributions in ways that would be challenging for other approaches; (2) the methodologies developed in artificial life and computational social science carry over directly to computational social creativity; and (3) the combination of computational social creativity with individual models of creativity presents significant opportunities and poses interesting challenges for the development of integrated models of creativity that have yet to be realized.

Development and application of diurnal thermal modeling for camouflage, concealment, and deception

NASA Astrophysics Data System (ADS)

Rodgers, Mark L. B.

2000-07-01

The art of camouflage is to make a military asset appear to be part of the natural environment: its background. In order to predict the likely performance of countermeasures in attaining this goal it is necessary to model the signatures of targets, backgrounds and the effect of countermeasures. A library of diurnal thermal models has been constructed covering a range of backgrounds from vegetated and non- vegetated surfaces to snow cover. These models, originally developed for Western Europe, have been validated successfully for theatres of operation from the arctic to the desert. This paper will show the basis for and development of physically based models for the diurnal thermal behavior both of these backgrounds and for major passive countermeasures: camouflage nets and continuous textile materials. The countermeasures set up significant challenges for the thermal modeler with their low but non-zero thermal inertial and the extent to which they influence local aerodynamic behavior. These challenges have been met and the necessary extensive validation has shown the ability of the models to predict successfully the behavior of in-service countermeasures.

Evaluation of a District-Wide Inservice Professional Development Program for Science Teachers: Challenges Faced and Lessons Learned.

ERIC Educational Resources Information Center

Dass, Pradeep Maxwell

Nation-wide dissemination of the Iowa Chautauqua Model for inservice professional development of K-12 science teachers has led to new professional development programs in many states. The Collier Chautauqua Program (CCP) implemented the Iowa Chautauqua model at the district level in Collier County, Florida. A formative evaluation of the…

Development of external regeneration models for FVS: Another wrench in the toolkit

Treesearch

Donald C. E. Robinson

2008-01-01

Despite more than three decades of development, only one full-featured regeneration model has been developed for the Forest Vegetation Simulator (FVS). Regeneration remains a challenging problem because of its all-or-none nature: the need for field inventories that span the vast range of stand structure conditions; the need to accommodate environmental and climatic...

Uses of Agent-Based Modeling for Health Communication: the TELL ME Case Study.

PubMed

Barbrook-Johnson, Peter; Badham, Jennifer; Gilbert, Nigel

2017-08-01

Government communication is an important management tool during a public health crisis, but understanding its impact is difficult. Strategies may be adjusted in reaction to developments on the ground and it is challenging to evaluate the impact of communication separately from other crisis management activities. Agent-based modeling is a well-established research tool in social science to respond to similar challenges. However, there have been few such models in public health. We use the example of the TELL ME agent-based model to consider ways in which a non-predictive policy model can assist policy makers. This model concerns individuals' protective behaviors in response to an epidemic, and the communication that influences such behavior. Drawing on findings from stakeholder workshops and the results of the model itself, we suggest such a model can be useful: (i) as a teaching tool, (ii) to test theory, and (iii) to inform data collection. We also plot a path for development of similar models that could assist with communication planning for epidemics.

ACTIVIS: Visual Exploration of Industry-Scale Deep Neural Network Models.

PubMed

Kahng, Minsuk; Andrews, Pierre Y; Kalro, Aditya; Polo Chau, Duen Horng

2017-08-30

While deep learning models have achieved state-of-the-art accuracies for many prediction tasks, understanding these models remains a challenge. Despite the recent interest in developing visual tools to help users interpret deep learning models, the complexity and wide variety of models deployed in industry, and the large-scale datasets that they used, pose unique design challenges that are inadequately addressed by existing work. Through participatory design sessions with over 15 researchers and engineers at Facebook, we have developed, deployed, and iteratively improved ACTIVIS, an interactive visualization system for interpreting large-scale deep learning models and results. By tightly integrating multiple coordinated views, such as a computation graph overview of the model architecture, and a neuron activation view for pattern discovery and comparison, users can explore complex deep neural network models at both the instance- and subset-level. ACTIVIS has been deployed on Facebook's machine learning platform. We present case studies with Facebook researchers and engineers, and usage scenarios of how ACTIVIS may work with different models.

Participation and occupation in occupational therapy models of practice: A discussion of possibilities and challenges.

PubMed

Larsson-Lund, Maria; Nyman, Anneli

2017-11-01

Occupation has been the focus in occupational therapy practice to greater or lesser degrees from a historical viewpoint. This evokes a need to discuss whether concepts that are added to our field will enhance or blur our focus on occupation. To explore how the concept of participation in the International Classification of Functioning, Disability and Health (ICF) is related to the concept of occupation by reviewing and comparing its use in three models of practice within occupational therapy. The aim was also to generate discussion on possibilities and challenges concerning the relationship of participation and occupation. The models reviewed were The Model of Human Occupation (MOHO), the Canadian Model of Occupational Performance and Engagement (CMOP-E) and the Occupational Therapy Intervention Process Model (OTIPM). The concept of participation was related to occupation in different ways in these models. Based on the review some challenges and considerations for occupational therapy were generated. Relating the concept of participation from the ICF to the concept of occupation in models of practice can be challenging. At the same time, relating the concepts can be a resource to develop occupational therapy and the understanding of occupational issues in society.

Five challenges in evolution and infectious diseases.

PubMed

Metcalf, C J E; Birger, R B; Funk, S; Kouyos, R D; Lloyd-Smith, J O; Jansen, V A A

2015-03-01

Evolution is a key aspect of the biology of many pathogens, driving processes ranging from immune escape to changes in virulence. Because evolution is inherently subject to feedbacks, and because pathogen evolution plays out at scales ranging from within-host to between-host and beyond, evolutionary questions provide special challenges to the modelling community. In this article, we provide an overview of five challenges in modelling the evolution of pathogens and their hosts, and point to areas for development, focussing in particular on the issue of linking theory and data. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

A recombinant vesicular stomatitis virus-based Lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses.

PubMed

Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz

2015-04-01

Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a "universal" LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.

Virtual Modeling for Cities of the Future. State-Of Art and Virtual Modeling for Cities of the Future. State-Of Art AN

NASA Astrophysics Data System (ADS)

Valencia, J.; Muñoz-Nieto, A.; Rodriguez-Gonzalvez, P.

2015-02-01

3D virtual modeling, visualization, dissemination and management of urban areas is one of the most exciting challenges that must face geomatics in the coming years. This paper aims to review, compare and analyze the new technologies, policies and software tools that are in progress to manage urban 3D information. It is assumed that the third dimension increases the quality of the model provided, allowing new approaches to urban planning, conservation and management of architectural and archaeological areas. Despite the fact that displaying 3D urban environments is an issue nowadays solved, there are some challenges to be faced by geomatics in the coming future. Displaying georeferenced linked information would be considered the first challenge. Another challenge to face is to improve the technical requirements if this georeferenced information must be shown in real time. Are there available software tools ready for this challenge? Are they useful to provide services required in smart cities? Throughout this paper, many practical examples that require 3D georeferenced information and linked data will be shown. Computer advances related to 3D spatial databases and software that are being developed to convert rendering virtual environment to a new enriched environment with linked information will be also analyzed. Finally, different standards that Open Geospatial Consortium has assumed and developed regarding the three-dimensional geographic information will be reviewed. Particular emphasis will be devoted on KML, LandXML, CityGML and the new IndoorGML.

Cracking the humanitarian logistic coordination challenge: lessons from the urban search and rescue community.

PubMed

Tatham, Peter; Spens, Karen

2016-04-01

The challenges of achieving successful inter-agency logistic coordination in preparing for and responding to natural disasters and complex emergencies are both well understood and well documented. However, although many of these challenges remain unresolved, the literature reveals that the organisations that form the urban search and rescue (USAR) community have attained a high level of coherence and interoperability that results in a highly efficient and effective response. Therefore, this paper uses the idea of 'borrowing' from other fields as it explores how the processes and procedures used by the USAR community might be applied to improve humanitarian logistic operations. The paper analyses the USAR model and explores how the resultant challenges might be addressed in a humanitarian logistic context. The paper recommends that further research be undertaken in order to develop a modified USAR model that could be operationalised by the international community of humanitarian logisticians. © 2016 The Author(s). Disasters © Overseas Development Institute, 2016.

Cell-free protein synthesis in micro compartments: building a minimal cell from biobricks.

PubMed

Jia, Haiyang; Heymann, Michael; Bernhard, Frank; Schwille, Petra; Kai, Lei

2017-10-25

The construction of a minimal cell that exhibits the essential characteristics of life is a great challenge in the field of synthetic biology. Assembling a minimal cell requires multidisciplinary expertise from physics, chemistry and biology. Scientists from different backgrounds tend to define the essence of 'life' differently and have thus proposed different artificial cell models possessing one or several essential features of living cells. Using the tools and methods of molecular biology, the bottom-up engineering of a minimal cell appears in reach. However, several challenges still remain. In particular, the integration of individual sub-systems that is required to achieve a self-reproducing cell model presents a complex optimization challenge. For example, multiple self-organisation and self-assembly processes have to be carefully tuned. We review advances and developments of new methods and techniques, for cell-free protein synthesis as well as micro-fabrication, for their potential to resolve challenges and to accelerate the development of minimal cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Modelling water use in global hydrological models: review, challenges and directions

NASA Astrophysics Data System (ADS)

Bierkens, M. F.; de Graaf, I.; Wada, Y.; Wanders, N.; Van Beek, L. P.

2017-12-01

During the late 1980s and early 1990s, awareness of the shortage of global water resources lead to the first detailed global water resources assessments using regional statistics of water use and observations of meteorological and hydrological variables. Shortly thereafter, the first macroscale hydrological models (MHM) appeared. In these models, blue water (i.e., surface water and renewable groundwater) availability was calculated by accumulating runoff over a stream network and comparing it with population densities or with estimated water demand for agriculture, industry and households. In this talk we review the evolution of human impact modelling in global land models with a focus on global water resources, touching upon developments of the last 15 years: i.e. calculating human water scarcity; estimating groundwater depletion; adding dams and reservoirs; fully integrating water use (demand, withdrawal, consumption, return flow) in the hydrology; simulating the effects of land use change. We show example studies for each of these steps. We identify We identify major challenges that hamper the further development of integrated water resources modelling. Examples of these are: 1) simulating reservoir operations; 2) including local infrastructure and redistribution; 3) using the correct allocations rules; 4) projecting future water demand and water use. For each of these challenges we signify promising directions for further research.

Prospectus: towards the development of high-fidelity models of wall turbulence at large Reynolds number

PubMed Central

Klewicki, J. C.; Chini, G. P.; Gibson, J. F.

2017-01-01

Recent and on-going advances in mathematical methods and analysis techniques, coupled with the experimental and computational capacity to capture detailed flow structure at increasingly large Reynolds numbers, afford an unprecedented opportunity to develop realistic models of high Reynolds number turbulent wall-flow dynamics. A distinctive attribute of this new generation of models is their grounding in the Navier–Stokes equations. By adhering to this challenging constraint, high-fidelity models ultimately can be developed that not only predict flow properties at high Reynolds numbers, but that possess a mathematical structure that faithfully captures the underlying flow physics. These first-principles models are needed, for example, to reliably manipulate flow behaviours at extreme Reynolds numbers. This theme issue of Philosophical Transactions of the Royal Society A provides a selection of contributions from the community of researchers who are working towards the development of such models. Broadly speaking, the research topics represented herein report on dynamical structure, mechanisms and transport; scale interactions and self-similarity; model reductions that restrict nonlinear interactions; and modern asymptotic theories. In this prospectus, the challenges associated with modelling turbulent wall-flows at large Reynolds numbers are briefly outlined, and the connections between the contributing papers are highlighted. This article is part of the themed issue ‘Toward the development of high-fidelity models of wall turbulence at large Reynolds number’. PMID:28167585

Prospectus: towards the development of high-fidelity models of wall turbulence at large Reynolds number.

PubMed

Klewicki, J C; Chini, G P; Gibson, J F

2017-03-13

Recent and on-going advances in mathematical methods and analysis techniques, coupled with the experimental and computational capacity to capture detailed flow structure at increasingly large Reynolds numbers, afford an unprecedented opportunity to develop realistic models of high Reynolds number turbulent wall-flow dynamics. A distinctive attribute of this new generation of models is their grounding in the Navier-Stokes equations. By adhering to this challenging constraint, high-fidelity models ultimately can be developed that not only predict flow properties at high Reynolds numbers, but that possess a mathematical structure that faithfully captures the underlying flow physics. These first-principles models are needed, for example, to reliably manipulate flow behaviours at extreme Reynolds numbers. This theme issue of Philosophical Transactions of the Royal Society A provides a selection of contributions from the community of researchers who are working towards the development of such models. Broadly speaking, the research topics represented herein report on dynamical structure, mechanisms and transport; scale interactions and self-similarity; model reductions that restrict nonlinear interactions; and modern asymptotic theories. In this prospectus, the challenges associated with modelling turbulent wall-flows at large Reynolds numbers are briefly outlined, and the connections between the contributing papers are highlighted.This article is part of the themed issue 'Toward the development of high-fidelity models of wall turbulence at large Reynolds number'. © 2017 The Author(s).

Modeling pedogenesis at multimillennium timescales: achievements and challenges

NASA Astrophysics Data System (ADS)

Finke, Peter

2013-04-01

The modeling of soil genesis is a particular case of modeling vadose zone processes, because of the variety in processes to be considered and its large (multimillennium) temporal extent. The particular relevancy of pedogenetic modeling for non-pedologists is that it involves the soil compartment carbon cycle. As most of these processes are driven by water flow, modeling hydrological processes is an inevitable component of (non-empirical) modeling of soil genesis. One particular challenge is that both slow and fast pedogenetic processes need to be accounted for. This overview summarizes the state of the art in this new branch of pedology, achievements made so far and current challenges, and is largely based on one particular pedon-scale soil evolution model, SoilGen. SoilGen is essentially a pedon-scale solute transport model that simulates unsaturated water flow, chemical equilibriums of various species with calcite, gypsum and gibbsite as precipitated phases, an exchange phase of Na, K, Ca, Mg, H and Al on clay and organic matter and a solution phase comprising various cations and anions. Additionally, a number of pedogenetic processes are simulated: C-cycling, chemical weathering of primary minerals, physical weathering of soil particles, bioturbation and clay migration. The model was applied onto a climosequence, a chronosequence, a toposequence and as part of a spatio-temporal soilscape reconstruction. Furthermore, the clay migration component has been calibrated and tested and so has the organic matter decomposition component. Quantitative comparisons between simulations and measurements resulted in the identification of possible improvements in the model and associated inputs, identified problems to be solved and identified the current application domain. Major challenges for process-based modeling in the vadose zone at multimillennium timescales can be divided into 4 groups: (i) Reconstruction of initial and boundary conditions; (ii) Accounting for evolution in soil properties such as soil texture and soil structure; (iii) Developing adequate calibration techniques; (iv) Maximizing computational efficiency. Reconstruction of initial and boundary conditions requires multidisciplinary inputs either derived from proxies or from combined vegetation and climate development models. So far, the combination of pedogenetic models and combined vegetation/climate models is rare. At pedogenetic timescales, soil characteristics that are usually considered constant become dynamic: texture, OC, bulk density, precipitated salts, minerals, etc. Interactions and feedbacks between these characteristics and associated hydrological properties need attention, e.g. via pedotransfer functions. The same can be stated for the development of soil structure and associated preferential flow, which is still a challenge. At multimillennium temporal extents, the combination of long model runtime and the fact that most calibration data represent the current stage of soil development requires a special approach. Model performance can be evaluated at various timescales using unconventional proxies. Finally, recognizing the fact that matter redistribution at the landscape scale is of paramount importance at multimillennium extent requires the formulation of computationally efficient 3D models. This will surely involve analysis of the tradeoff between process detail, model accuracy, required boundary inputs and model runtime.

Challenges in Reproducibility, Replicability, and Comparability of Computational Models and Tools for Neuronal and Glial Networks, Cells, and Subcellular Structures.

PubMed

Manninen, Tiina; Aćimović, Jugoslava; Havela, Riikka; Teppola, Heidi; Linne, Marja-Leena

2018-01-01

The possibility to replicate and reproduce published research results is one of the biggest challenges in all areas of science. In computational neuroscience, there are thousands of models available. However, it is rarely possible to reimplement the models based on the information in the original publication, let alone rerun the models just because the model implementations have not been made publicly available. We evaluate and discuss the comparability of a versatile choice of simulation tools: tools for biochemical reactions and spiking neuronal networks, and relatively new tools for growth in cell cultures. The replicability and reproducibility issues are considered for computational models that are equally diverse, including the models for intracellular signal transduction of neurons and glial cells, in addition to single glial cells, neuron-glia interactions, and selected examples of spiking neuronal networks. We also address the comparability of the simulation results with one another to comprehend if the studied models can be used to answer similar research questions. In addition to presenting the challenges in reproducibility and replicability of published results in computational neuroscience, we highlight the need for developing recommendations and good practices for publishing simulation tools and computational models. Model validation and flexible model description must be an integral part of the tool used to simulate and develop computational models. Constant improvement on experimental techniques and recording protocols leads to increasing knowledge about the biophysical mechanisms in neural systems. This poses new challenges for computational neuroscience: extended or completely new computational methods and models may be required. Careful evaluation and categorization of the existing models and tools provide a foundation for these future needs, for constructing multiscale models or extending the models to incorporate additional or more detailed biophysical mechanisms. Improving the quality of publications in computational neuroscience, enabling progressive building of advanced computational models and tools, can be achieved only through adopting publishing standards which underline replicability and reproducibility of research results.

Challenges in Reproducibility, Replicability, and Comparability of Computational Models and Tools for Neuronal and Glial Networks, Cells, and Subcellular Structures

PubMed Central

Manninen, Tiina; Aćimović, Jugoslava; Havela, Riikka; Teppola, Heidi; Linne, Marja-Leena

2018-01-01

The possibility to replicate and reproduce published research results is one of the biggest challenges in all areas of science. In computational neuroscience, there are thousands of models available. However, it is rarely possible to reimplement the models based on the information in the original publication, let alone rerun the models just because the model implementations have not been made publicly available. We evaluate and discuss the comparability of a versatile choice of simulation tools: tools for biochemical reactions and spiking neuronal networks, and relatively new tools for growth in cell cultures. The replicability and reproducibility issues are considered for computational models that are equally diverse, including the models for intracellular signal transduction of neurons and glial cells, in addition to single glial cells, neuron-glia interactions, and selected examples of spiking neuronal networks. We also address the comparability of the simulation results with one another to comprehend if the studied models can be used to answer similar research questions. In addition to presenting the challenges in reproducibility and replicability of published results in computational neuroscience, we highlight the need for developing recommendations and good practices for publishing simulation tools and computational models. Model validation and flexible model description must be an integral part of the tool used to simulate and develop computational models. Constant improvement on experimental techniques and recording protocols leads to increasing knowledge about the biophysical mechanisms in neural systems. This poses new challenges for computational neuroscience: extended or completely new computational methods and models may be required. Careful evaluation and categorization of the existing models and tools provide a foundation for these future needs, for constructing multiscale models or extending the models to incorporate additional or more detailed biophysical mechanisms. Improving the quality of publications in computational neuroscience, enabling progressive building of advanced computational models and tools, can be achieved only through adopting publishing standards which underline replicability and reproducibility of research results. PMID:29765315

A New Direction for Technology-Based Economic Development: The Role of Innovation Intermediaries

ERIC Educational Resources Information Center

Bendis, Richard A.; Seline, Richard S.; Byler, Ethan J.

2008-01-01

Accelerating innovation to drive economic growth is the foremost goal for technology-based economic development organizations today. Realizing this goal through programmes is challenged by limited and outdated operating models. The authors outline their 21st Century Innovation Intermediary model, which pairs commercialization with regional…

Community Dissemination of the Early Start Denver Model: Implications for Science and Practice

ERIC Educational Resources Information Center

Vismara, Laurie A.; Young, Gregory S.; Rogers, Sally J.

2013-01-01

The growing number of Autism Spectrum Disorder cases exceeds the services available for these children. This increase challenges both researchers and service providers to develop systematic, effective dissemination strategies for transporting university research models to community early intervention (EI) programs. The current study developed an…

Midlife Eriksonian Psychosocial Development: Setting the Stage for Late-Life Cognitive and Emotional Health

ERIC Educational Resources Information Center

Malone, Johanna C.; Liu, Sabrina R.; Vaillant, George E.; Rentz, Dorene M.; Waldinger, Robert J.

2016-01-01

Erikson's (1950) model of adult psychosocial development outlines the significance of successful involvement within one's relationships, work, and community for healthy aging. He theorized that the consequences of not meeting developmental challenges included stagnation and emotional despair. Drawing on this model, the present study uses…

Wisconsin's Model Academic Standards for Music.

ERIC Educational Resources Information Center

Nikolay, Pauli; Grady, Susan; Stefonek, Thomas

To assist parents and educators in preparing students for the 21st century, Wisconsin citizens have become involved in the development of challenging academic standards in 12 curricular areas. Having clear standards for students and teachers makes it possible to develop rigorous local curricula and valid, reliable assessments. This model of…

New Models of Hybrid Leadership in Global Higher Education

ERIC Educational Resources Information Center

Tonini, Donna C.; Burbules, Nicholas C.; Gunsalus, C. K.

2016-01-01

This manuscript highlights the development of a leadership preparation program known as the Nanyang Technological University Leadership Academy (NTULA), exploring the leadership challenges unique to a university undergoing rapid growth in a highly multicultural context, and the hybrid model of leadership it developed in response to globalization.…

A Model for Conducting and Assessing Interdisciplinary Undergraduate Dissertations

ERIC Educational Resources Information Center

Engström, Henrik

2015-01-01

This paper presents an effort to create a unified model for conducting and assessing undergraduate dissertations, shared by all disciplines involved in computer game development at a Swedish university. Computer game development includes technology-oriented disciplines as well as disciplines with aesthetical traditions. The challenge has been to…

US EPA - A*Star Partnership - Accelerating the Acceptance of ...

EPA Pesticide Factsheets

The path for incorporating new alternative methods and technologies into quantitative chemical risk assessment poses a diverse set of scientific challenges. Some of these challenges include development of relevant and predictive test systems and computational models to integrate and extrapolate experimental data, and rapid characterization and acceptance of these systems and models. The series of presentations will highlight a collaborative effort between the U.S. Environmental Protection Agency (EPA) and the Agency for Science, Technology and Research (A*STAR) that is focused on developing and applying experimental and computational models for predicting chemical-induced liver and kidney toxicity, brain angiogenesis, and blood-brain-barrier formation. In addressing some of these challenges, the U.S. EPA and A*STAR collaboration will provide a glimpse of what chemical risk assessments could look like in the 21st century. Presentation on US EPA – A*STAR Partnership at international symposium on Accelerating the acceptance of next-generation sciences and their application to regulatory risk assessment in Singapore.

Development of a sheep challenge model for Rift Valley fever.

PubMed

Faburay, Bonto; Gaudreault, Natasha N; Liu, Qinfang; Davis, A Sally; Shivanna, Vinay; Sunwoo, Sun Young; Lang, Yuekun; Morozov, Igor; Ruder, Mark; Drolet, Barbara; Scott McVey, D; Ma, Wenjun; Wilson, William; Richt, Juergen A

2016-02-01

Rift Valley fever (RVF) is a zoonotic disease that causes severe epizootics in ruminants, characterized by mass abortion and high mortality rates in younger animals. The development of a reliable challenge model is an important prerequisite for evaluation of existing and novel vaccines. A study aimed at comparing the pathogenesis of RVF virus infection in US sheep using two genetically different wild type strains of the virus (SA01-1322 and Kenya-128B-15) was performed. A group of sheep was inoculated with both strains and all infected sheep manifested early-onset viremia accompanied by a transient increase in temperatures. The Kenya-128B-15 strain manifested higher virulence compared to SA01-1322 by inducing more severe liver damage, and longer and higher viremia. Genome sequence analysis revealed sequence variations between the two isolates, which potentially could account for the observed phenotypic differences. We conclude that Kenya-128B-15 sheep infection represents a good and virulent challenge model for RVF. Copyright © 2015 Elsevier Inc. All rights reserved.

EvalPartners: Facilitating the Development of a New Model of Voluntary Organization for Professional Evaluation to Support the Development of National Evaluation Capacities

ERIC Educational Resources Information Center

Kosheleva, Natalia; Segone, Marco

2013-01-01

In many less developed democracies Voluntary Organizations for Professional Evaluation (VOPEs) face the challenges of low demand for evaluation and the resulting low economic capacity of national evaluation communities. The VOPE model that evolved in well-developed democracies is not directly applicable under these circumstances, so a new model…

The Use of Dynamic Stochastic Social Behavior Models to Produce Likelihood Functions for Risk Modeling of Proliferation and Terrorist Attacks

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

Young, Jonathan; Thompson, Sandra E.; Brothers, Alan J.

The ability to estimate the likelihood of future events based on current and historical data is essential to the decision making process of many government agencies. Successful predictions related to terror events and characterizing the risks will support development of options for countering these events. The predictive tasks involve both technical and social component models. The social components have presented a particularly difficult challenge. This paper outlines some technical considerations of this modeling activity. Both data and predictions associated with the technical and social models will likely be known with differing certainties or accuracies – a critical challenge is linkingmore » across these model domains while respecting this fundamental difference in certainty level. This paper will describe the technical approach being taken to develop the social model and identification of the significant interfaces between the technical and social modeling in the context of analysis of diversion of nuclear material.« less

New Challenges for Intervertebral Disc Treatment Using Regenerative Medicine

PubMed Central

Masuda, Koichi

2010-01-01

The development of tissue engineering therapies for the intervertebral disc is challenging due to ambiguities of disease and pain mechanisms in patients, and lack of consensus on preclinical models for safety and efficacy testing. Although the issues associated with model selection for studying orthopedic diseases or treatments have been discussed often, the multifaceted challenges associated with developing intervertebral disc tissue engineering therapies require special discussion. This review covers topics relevant to the clinical translation of tissue-engineered technologies: (1) the unmet clinical need, (2) appropriate models for safety and efficacy testing, (3) the need for standardized model systems, and (4) the translational pathways leading to a clinical trial. For preclinical evaluation of new therapies, we recommend establishing biologic plausibility of efficacy and safety using models of increasing complexity, starting with cell culture, small animals (rats and rabbits), and then large animals (goat and minipig) that more closely mimic nutritional, biomechanical, and surgical realities of human application. The use of standardized and reproducible experimental procedures and outcome measures is critical for judging relative efficacy. Finally, success will hinge on carefully designed clinical trials with well-defined patient selection criteria, gold-standard controls, and objective outcome metrics to assess performance in the early postoperative period. PMID:19903086

Sobol Sensitivity Analysis: A Tool to Guide the Development and Evaluation of Systems Pharmacology Models

PubMed Central

Trame, MN; Lesko, LJ

2015-01-01

A systems pharmacology model typically integrates pharmacokinetic, biochemical network, and systems biology concepts into a unifying approach. It typically consists of a large number of parameters and reaction species that are interlinked based upon the underlying (patho)physiology and the mechanism of drug action. The more complex these models are, the greater the challenge of reliably identifying and estimating respective model parameters. Global sensitivity analysis provides an innovative tool that can meet this challenge. CPT Pharmacometrics Syst. Pharmacol. (2015) 4, 69–79; doi:10.1002/psp4.6; published online 25 February 2015 PMID:27548289

Resistance and Protective Immunity in Redfish Lake Sockeye Salmon Exposed to M Type Infectious Hematopoietic Necrosis Virus (IHNV)

USGS Publications Warehouse

Kurath, Gael; Garver, Kyle; Purcell, Maureen K.; LaPatra, Scott E.

2010-01-01

Differential virulence of infectious hematopoietic necrosis virus (IHNV) isolates from the U and M phylogenetic subgroups is clearly evident in the Redfish Lake (RFL) strain of sockeye salmon Oncorhynchus nerka. In these fish, experimental immersion challenges with U isolates cause extremely high mortality and M isolates cause low or no mortality. When survivors of M virus immersion challenges were exposed to a secondary challenge with virulent U type virus they experienced high mortality, indicating that the primary M challenge did not elicit protective immunity. Delivery of a moderate dose (2 × 104 plaque-forming units [PFU]/fish) of virus by intraperitoneal injection challenge did not overcome RFL sockeye salmon resistance to M type IHNV. Injection challenge with a high dose (5 × 106 PFU/fish) of M type virus caused 10% mortality, and in this case survivors did develop protective immunity against a secondary U type virus challenge. Thus, although it is possible for M type IHNV to elicit cross-protective immunity in this disease model, it does not develop after immersion challenge despite entry, transient replication of M virus to low levels, stimulation of innate immune genes, and development of neutralizing antibodies in some fish.

Beyond the rhetoric: what do we mean by a 'model of care'?

PubMed

Davidson, Patricia; Halcomb, Elizabeth; Hickman, L; Phillips, J; Graham, B

2006-01-01

Contemporary health care systems are constantly challenged to revise traditional methods of health care delivery. These challenges are multifaceted and stem from: (1) novel pharmacological and non-pharmacological treatments; (2) changes in consumer demands and expectations; (3) fiscal and resource constraints; (4) changes in societal demographics in particular the ageing of society; (5) an increasing burden of chronic disease; (6) documentation of limitations in traditional health care delivery; (7) increased emphasis on transparency, accountability, evidence-based practice (EBP) and clinical governance structures; and (8) the increasing cultural diversity of the community. These challenges provoke discussion of potential alternative models of care, with scant reference to defining what constitutes a model of care. This paper aims to define what is meant by the term 'model of care' and document the pragmatic systems and processes necessary to develop, plan, implement and evaluate novel models of care delivery. Searches of electronic databases, the reference lists of published materials, policy documents and the Internet were conducted using key words including 'model*', 'framework*', 'models, theoretical' and 'nursing models, theoretical'. The collated material was then analysed and synthesised into this review. This review determined that in addition to key conceptual and theoretical perspectives, quality improvement theory (eg. collaborative methodology), project management methods and change management theory inform both pragmatic and conceptual elements of a model of care. Crucial elements in changing health care delivery through the development of innovative models of care include the planning, development, implementation, evaluation and assessment of the sustainability of the new model. Regardless of whether change in health care delivery is attempted on a micro basis (eg. ward level) or macro basis (eg. national or state system) in order to achieve sustainable, effective and efficient changes a well-planned, systematic process is essential.

Bioreactor Technologies to Support Liver Function In Vitro

PubMed Central

Ebrahimkhani, Mohammad R; Neiman, Jaclyn A Shepard; Raredon, Micah Sam B; Hughes, David J; Griffith, Linda G

2014-01-01

Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drive efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models. PMID:24607703

Challenges and gaps for energy planning models in the developing-world context

NASA Astrophysics Data System (ADS)

Debnath, Kumar Biswajit; Mourshed, Monjur

2018-03-01

Energy planning models (EPMs) support multi-criteria assessments of the impact of energy policies on the economy and environment. Most EPMs originated in developed countries and are primarily aimed at reducing greenhouse gas emissions while enhancing energy security. In contrast, most, if not all, developing countries are predominantly concerned with increasing energy access. Here, we review thirty-four widely used EPMs to investigate their applicability to developing countries and find an absence of consideration of the objectives, challenges, and nuances of the developing context. Key deficiencies arise from the lack of deliberation of the low energy demand resulting from lack of access and availability of supply. Other inadequacies include the lack of consideration of socio-economic nuances such as the prevalence of corruption and resulting cost inflation, the methods for adequately addressing the shortcomings in data quality, availability and adequacy, and the effects of climate change. We argue for further research on characterization and modelling of suppressed demand, climate change impacts, and socio-political feedback in developing countries, and the development of contextual EPMs.

Rapid development of entity-based data models for bioinformatics with persistence object-oriented design and structured interfaces.

PubMed

Ezra Tsur, Elishai

2017-01-01

Databases are imperative for research in bioinformatics and computational biology. Current challenges in database design include data heterogeneity and context-dependent interconnections between data entities. These challenges drove the development of unified data interfaces and specialized databases. The curation of specialized databases is an ever-growing challenge due to the introduction of new data sources and the emergence of new relational connections between established datasets. Here, an open-source framework for the curation of specialized databases is proposed. The framework supports user-designed models of data encapsulation, objects persistency and structured interfaces to local and external data sources such as MalaCards, Biomodels and the National Centre for Biotechnology Information (NCBI) databases. The proposed framework was implemented using Java as the development environment, EclipseLink as the data persistency agent and Apache Derby as the database manager. Syntactic analysis was based on J3D, jsoup, Apache Commons and w3c.dom open libraries. Finally, a construction of a specialized database for aneurysms associated vascular diseases is demonstrated. This database contains 3-dimensional geometries of aneurysms, patient's clinical information, articles, biological models, related diseases and our recently published model of aneurysms' risk of rapture. Framework is available in: http://nbel-lab.com.

A physiome interoperability roadmap for personalized drug development

PubMed Central

2016-01-01

The goal of developing therapies and dosage regimes for characterized subgroups of the general population can be facilitated by the use of simulation models able to incorporate information about inter-individual variability in drug disposition (pharmacokinetics), toxicity and response effect (pharmacodynamics). Such observed variability can have multiple causes at various scales, ranging from gross anatomical differences to differences in genome sequence. Relevant data for many of these aspects, particularly related to molecular assays (known as ‘-omics’), are available in online resources, but identification and assignment to appropriate model variables and parameters is a significant bottleneck in the model development process. Through its efforts to standardize annotation with consequent increase in data usability, the human physiome project has a vital role in improving productivity in model development and, thus, the development of personalized therapy regimes. Here, we review the current status of personalized medicine in clinical practice, outline some of the challenges that must be overcome in order to expand its applicability, and discuss the relevance of personalized medicine to the more widespread challenges being faced in drug discovery and development. We then review some of (i) the key data resources available for use in model development and (ii) the potential areas where advances made within the physiome modelling community could contribute to physiologically based pharmacokinetic and physiologically based pharmacokinetic/pharmacodynamic modelling in support of personalized drug development. We conclude by proposing a roadmap to further guide the physiome community in its on-going efforts to improve data usability, and integration with modelling efforts in the support of personalized medicine development. PMID:27051513

Towards 2000 and Beyond: Preparation of Educational Managers in India.

ERIC Educational Resources Information Center

Sapra, C. L.

1993-01-01

Discusses challenges facing educational management in India resulting from demographic change, social demand for education, economic need for trained manpower. Attempts to develop social model for year 2000, reflecting concerns for strength of India's democracy and secularization. Educational managers will be challenged to achieve universalization…

Challenges Associated With Applying Physiologically Based Pharmacokinetic Modeling for Public Health Decision-Making.

PubMed

Tan, Yu-Mei; Worley, Rachel R; Leonard, Jeremy A; Fisher, Jeffrey W

2018-04-01

The development and application of physiologically based pharmacokinetic (PBPK) models in chemical toxicology have grown steadily since their emergence in the 1980s. However, critical evaluation of PBPK models to support public health decision-making across federal agencies has thus far occurred for only a few environmental chemicals. In order to encourage decision-makers to embrace the critical role of PBPK modeling in risk assessment, several important challenges require immediate attention from the modeling community. The objective of this contemporary review is to highlight 3 of these challenges, including: (1) difficulties in recruiting peer reviewers with appropriate modeling expertise and experience; (2) lack of confidence in PBPK models for which no tissue/plasma concentration data exist for model evaluation; and (3) lack of transferability across modeling platforms. Several recommendations for addressing these 3 issues are provided to initiate dialog among members of the PBPK modeling community, as these issues must be overcome for the field of PBPK modeling to advance and for PBPK models to be more routinely applied in support of public health decision-making.

Product Line Acquisition in the DoD: The Promise, The Challenges

DTIC Science & Technology

1999-12-01

Organizational Structure 8 3.4 Providing an Appropriate Funding Model 9 3.5 Developing and Implementing an Acquisition Strategy 10 3.6 Contractor Interface...providing an appropriate funding model • achieving the right organizational structure • developing and implementing an acquisition strategy • contractor...organizational change rather than attempt a risky enterprise overhaul. 3.4 Providing an Appropriate Funding Model The funding model is closely

Challenges in the development of therapeutics for narcolepsy

PubMed Central

Black, Sarah Wurts; Yamanaka, Akihiro; Kilduff, Thomas S.

2016-01-01

Narcolepsy is a neurological disorder that afflicts 1 in 2000 individuals and is characterized by excessive daytime sleepiness and cataplexy—a sudden loss of muscle tone triggered by positive emotions. Features of narcolepsy include dysregulation of arousal state boundaries as well as autonomic and metabolic disturbances. Disruption of neurotransmission through the hypocretin/orexin (Hcrt) system, usually by degeneration of the HCRT-producing neurons in the posterior hypothalamus, results in narcolepsy. The cause of Hcrt neurodegeneration is unknown but thought to be related to autoimmune processes. Current treatments for narcolepsy are symptomatic, including wake-promoting therapeutics that increase presynaptic dopamine release and anticataplectic agents that activate monoaminergic neurotransmission. Sodium oxybate is the only medication approved by the US Food and Drug Administration that alleviates both sleep/wake disturbances and cataplexy. Development of therapeutics for narcolepsy has been challenged by historical misunderstanding of the disease, its many disparate symptoms and, until recently, its unknown etiology. Animal models have been essential to elucidating the neuropathology underlying narcolepsy. These models have also aided understanding the neurobiology of the Hcrt system, mechanisms of cataplexy, and the pharmacology of narcolepsy medications. Transgenic rodent models will be critical in the development of novel therapeutics for the treatment of narcolepsy, particularly efforts directed to overcome challenges in the development of hypocretin replacement therapy. PMID:26721620

Challenges in the development of therapeutics for narcolepsy.

PubMed

Black, Sarah Wurts; Yamanaka, Akihiro; Kilduff, Thomas S

2017-05-01

Narcolepsy is a neurological disorder that afflicts 1 in 2000 individuals and is characterized by excessive daytime sleepiness and cataplexy-a sudden loss of muscle tone triggered by positive emotions. Features of narcolepsy include dysregulation of arousal state boundaries as well as autonomic and metabolic disturbances. Disruption of neurotransmission through the hypocretin/orexin (Hcrt) system, usually by degeneration of the HCRT-producing neurons in the posterior hypothalamus, results in narcolepsy. The cause of Hcrt neurodegeneration is unknown but thought to be related to autoimmune processes. Current treatments for narcolepsy are symptomatic, including wake-promoting therapeutics that increase presynaptic dopamine release and anticataplectic agents that activate monoaminergic neurotransmission. Sodium oxybate is the only medication approved by the US Food and Drug Administration that alleviates both sleep/wake disturbances and cataplexy. Development of therapeutics for narcolepsy has been challenged by historical misunderstanding of the disease, its many disparate symptoms and, until recently, its unknown etiology. Animal models have been essential to elucidating the neuropathology underlying narcolepsy. These models have also aided understanding the neurobiology of the Hcrt system, mechanisms of cataplexy, and the pharmacology of narcolepsy medications. Transgenic rodent models will be critical in the development of novel therapeutics for the treatment of narcolepsy, particularly efforts directed to overcome challenges in the development of hypocretin replacement therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Training of Evaluators in the Third World: Implementation of the Action Training Model (ATM) in Kenya and Botswana.

ERIC Educational Resources Information Center

Bhola, H. S.

The Action Training Model (ATM) was developed for the delivery of evaluation training to development workers in Kenya and Botswana and implemented under the aegis of the German Foundation for International Development. Training of evaluators is a challenge in any context, but in the Third World environment, evaluation training offers special…

A 3-D Approach for Teaching and Learning about Surface Water Systems through Computational Thinking, Data Visualization and Physical Models

NASA Astrophysics Data System (ADS)

Caplan, B.; Morrison, A.; Moore, J. C.; Berkowitz, A. R.

2017-12-01

Understanding water is central to understanding environmental challenges. Scientists use `big data' and computational models to develop knowledge about the structure and function of complex systems, and to make predictions about changes in climate, weather, hydrology, and ecology. Large environmental systems-related data sets and simulation models are difficult for high school teachers and students to access and make sense of. Comp Hydro, a collaboration across four states and multiple school districts, integrates computational thinking and data-related science practices into water systems instruction to enhance development of scientific model-based reasoning, through curriculum, assessment and teacher professional development. Comp Hydro addresses the need for 1) teaching materials for using data and physical models of hydrological phenomena, 2) building teachers' and students' comfort or familiarity with data analysis and modeling, and 3) infusing the computational knowledge and practices necessary to model and visualize hydrologic processes into instruction. Comp Hydro teams in Baltimore, MD and Fort Collins, CO are integrating teaching about surface water systems into high school courses focusing on flooding (MD) and surface water reservoirs (CO). This interactive session will highlight the successes and challenges of our physical and simulation models in helping teachers and students develop proficiency with computational thinking about surface water. We also will share insights from comparing teacher-led vs. project-led development of curriculum and our simulations.

BioEarth: Envisioning and developing a new regional earth system model to inform natural and agricultural resource management

DOE PAGES

Adam, Jennifer C.; Stephens, Jennie C.; Chung, Serena H.; ...

2014-04-24

Uncertainties in global change impacts, the complexities associated with the interconnected cycling of nitrogen, carbon, and water present daunting management challenges. Existing models provide detailed information on specific sub-systems (e.g., land, air, water, and economics). An increasing awareness of the unintended consequences of management decisions resulting from interconnectedness of these sub-systems, however, necessitates coupled regional earth system models (EaSMs). Decision makers’ needs and priorities can be integrated into the model design and development processes to enhance decision-making relevance and “usability” of EaSMs. BioEarth is a research initiative currently under development with a focus on the U.S. Pacific Northwest region thatmore » explores the coupling of multiple stand-alone EaSMs to generate usable information for resource decision-making. Direct engagement between model developers and non-academic stakeholders involved in resource and environmental management decisions throughout the model development process is a critical component of this effort. BioEarth utilizes a bottom-up approach for its land surface model that preserves fine spatial-scale sensitivities and lateral hydrologic connectivity, which makes it unique among many regional EaSMs. Here, we describe the BioEarth initiative and highlights opportunities and challenges associated with coupling multiple stand-alone models to generate usable information for agricultural and natural resource decision-making.« less

Developing a theoretical framework for complex community-based interventions.

PubMed

Angeles, Ricardo N; Dolovich, Lisa; Kaczorowski, Janusz; Thabane, Lehana

2014-01-01

Applying existing theories to research, in the form of a theoretical framework, is necessary to advance knowledge from what is already known toward the next steps to be taken. This article proposes a guide on how to develop a theoretical framework for complex community-based interventions using the Cardiovascular Health Awareness Program as an example. Developing a theoretical framework starts with identifying the intervention's essential elements. Subsequent steps include the following: (a) identifying and defining the different variables (independent, dependent, mediating/intervening, moderating, and control); (b) postulating mechanisms how the independent variables will lead to the dependent variables; (c) identifying existing theoretical models supporting the theoretical framework under development; (d) scripting the theoretical framework into a figure or sets of statements as a series of hypotheses, if/then logic statements, or a visual model; (e) content and face validation of the theoretical framework; and (f) revising the theoretical framework. In our example, we combined the "diffusion of innovation theory" and the "health belief model" to develop our framework. Using the Cardiovascular Health Awareness Program as the model, we demonstrated a stepwise process of developing a theoretical framework. The challenges encountered are described, and an overview of the strategies employed to overcome these challenges is presented.

Scientific challenges and opportunities in developing novel vaccines for the emerging and developing markets: New Technologies in Emerging Markets, October 16th-18th 2012, World Vaccine Congress, Lyon.

PubMed

Kochhar, Sonali

2013-04-01

Vaccines have had a major role in enhancing the quality of life and increasing life expectancy. Despite these successes and the development of new vaccine technologies, there remain multiple infectious diseases including AIDS, malaria and tuberculosis that require effective prophylactic vaccines. New and traditional technologies have a role in the development and delivery of the new vaccine candidates. The scientific challenges, opportunities and funding models for developing vaccines for low resource settings are highlighted here.

Computational fluid dynamics-habitat suitability index (CFD-HSI) modelling as an exploratory tool for assessing passability of riverine migratory challenge zones for fish

USGS Publications Warehouse

Haro, Alexander J.; Chelminski, Michael; Dudley, Robert W.

2015-01-01

We developed two-dimensional computational fluid hydraulics-habitat suitability index (CFD-HSI) models to identify and qualitatively assess potential zones of shallow water depth and high water velocity that may present passage challenges for five major anadromous fish species in a 2.63-km reach of the main stem Penobscot River, Maine, as a result of a dam removal downstream of the reach. Suitability parameters were based on distribution of fish lengths and body depths and transformed to cruising, maximum sustained and sprint swimming speeds. Zones of potential depth and velocity challenges were calculated based on the hydraulic models; ability of fish to pass a challenge zone was based on the percent of river channel that the contiguous zone spanned and its maximum along-current length. Three river flows (low: 99.1 m3 sec-1; normal: 344.9 m3 sec-1; and high: 792.9 m3 sec-1) were modelled to simulate existing hydraulic conditions and hydraulic conditions simulating removal of a dam at the downstream boundary of the reach. Potential depth challenge zones were nonexistent for all low-flow simulations of existing conditions for deeper-bodied fishes. Increasing flows for existing conditions and removal of the dam under all flow conditions increased the number and size of potential velocity challenge zones, with the effects of zones being more pronounced for smaller species. The two-dimensional CFD-HSI model has utility in demonstrating gross effects of flow and hydraulic alteration, but may not be as precise a predictive tool as a three-dimensional model. Passability of the potential challenge zones cannot be precisely quantified for two-dimensional or three-dimensional models due to untested assumptions and incomplete data on fish swimming performance and behaviours.

Turning challenge into opportunity: what home care needs to know about Medicare advantage.

PubMed

Twiss, Amanda; Schwien, Tina

2008-01-01

With multiple payors having different rules, paperwork, and payment models, the challenge is that MA plans typically focus time and attention on the providers associated with the highest costs--hospitals and physicians. With little attention being paid to the home health providers, MA plans cost containment measures and operational practices create challenges for providers developing an overall treatment plan for a patient's episode of care.

Development and validation of quasi-steady-state heat pump water heater model having stratified water tank and wrapped-tank condenser

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

Shen, Bo; Nawaz, Kashif; Baxter, Van D.

Heat pump water heater systems (HPWH) introduce new challenges for design and modeling tools, because they require vapor compression system balanced with a water storage tank. In addition, a wrapped-tank condenser coil has strong coupling with a stratified water tank, which leads HPWH simulation to a transient process. To tackle these challenges and deliver an effective, hardware-based HPWH equipment design tool, a quasi-steady-state HPWH model was developed based on the DOE/ORNL Heat Pump Design Model (HPDM). Two new component models were added via this study. One is a one-dimensional stratified water tank model, an improvement to the open-source EnergyPlus watermore » tank model, by introducing a calibration factor to account for bulk mixing effect due to water draws, circulations, etc. The other is a wrapped-tank condenser coil model, using a segment-to-segment modeling approach. In conclusion, the HPWH system model was validated against available experimental data. After that, the model was used for parametric simulations to determine the effects of various design factors.« less

Development and validation of quasi-steady-state heat pump water heater model having stratified water tank and wrapped-tank condenser

DOE PAGES

Shen, Bo; Nawaz, Kashif; Baxter, Van D.; ...

2017-10-31

Heat pump water heater systems (HPWH) introduce new challenges for design and modeling tools, because they require vapor compression system balanced with a water storage tank. In addition, a wrapped-tank condenser coil has strong coupling with a stratified water tank, which leads HPWH simulation to a transient process. To tackle these challenges and deliver an effective, hardware-based HPWH equipment design tool, a quasi-steady-state HPWH model was developed based on the DOE/ORNL Heat Pump Design Model (HPDM). Two new component models were added via this study. One is a one-dimensional stratified water tank model, an improvement to the open-source EnergyPlus watermore » tank model, by introducing a calibration factor to account for bulk mixing effect due to water draws, circulations, etc. The other is a wrapped-tank condenser coil model, using a segment-to-segment modeling approach. In conclusion, the HPWH system model was validated against available experimental data. After that, the model was used for parametric simulations to determine the effects of various design factors.« less

Treat All Students like the "Best" Students

ERIC Educational Resources Information Center

Bottoms, Gene

2007-01-01

What would happen if schools offered all students the same challenges and opportunities that some schools now offer only their "best" students? The Southern Regional Education Board addressed that question in 1987, when it developed the High Schools That Work Model. Blending challenging college-preparatory content with modern vocational and…

Teachers' Perceptions of Challenging Student Behaviours in Model Inner City Schools

ERIC Educational Resources Information Center

McCready, Lance T.; Soloway, Geoffrey B.

2010-01-01

Elementary teachers often cite challenging student behaviours and classroom management as areas of concern and therefore priorities for professional development. In this paper, the authors discuss the findings from a two-year research project, Sociocultural Perspectives on Behaviour and Classroom Management (SPBCM). SPBCM examined the social and…

A Perkins Challenge: Assessing Technical Skills in CTE

ERIC Educational Resources Information Center

Stone, James R., III

2009-01-01

Federal law requires state to develop performance measures and data-collection systems for secondary and postsecondary technical-skill attainment. This poses many challenges, such as defining a technical skills, measurement and when to assess students. In this article, the author outlines various assessment models and looks at the challenges…

Correspondence between Traditional Models of Functional Analysis and a Functional Analysis of Manding Behavior

ERIC Educational Resources Information Center

LaRue, Robert H.; Sloman, Kimberly N.; Weiss, Mary Jane; Delmolino, Lara; Hansford, Amy; Szalony, Jill; Madigan, Ryan; Lambright, Nathan M.

2011-01-01

Functional analysis procedures have been effectively used to determine the maintaining variables for challenging behavior and subsequently develop effective interventions. However, fear of evoking dangerous topographies of maladaptive behavior and concerns for reinforcing infrequent maladaptive behavior present challenges for people working in…

Improving on Army Field Gauze for Lethal Vascular Injuries: Challenges in Dressing Development

USDA-ARS?s Scientific Manuscript database

Accounting for half of all deaths, uncontrolled hemorrhage remains the leading cause of death on the battlefield. Gaining hemostatic control of lethal vascular injuries sustained in combat using topical agents remains a challenge. Recent animal testing using a lethal arterial injury model compared a...

A Project Team Analysis Using Tuckman's Model of Small-Group Development.

PubMed

Natvig, Deborah; Stark, Nancy L

2016-12-01

Concerns about equitable workloads for nursing faculty have been well documented, yet a standardized system for workload management does not exist. A project team was challenged to establish an academic workload management system when two dissimilar universities were consolidated. Tuckman's model of small-group development was used as the framework for the analysis of processes and effectiveness of a workload project team. Agendas, notes, and meeting minutes were used as the primary sources of information. Analysis revealed the challenges the team encountered. Utilization of a team charter was an effective tool in guiding the team to become a highly productive group. Lessons learned from the analysis are discussed. Guiding a diverse group into a highly productive team is complex. The use of Tuckman's model of small-group development provided a systematic mechanism to review and understand group processes and tasks. [J Nurs Educ. 2016;55(12):675-681.]. Copyright 2016, SLACK Incorporated.

Theoretical models for coronary vascular biomechanics: Progress & challenges

PubMed Central

Waters, Sarah L.; Alastruey, Jordi; Beard, Daniel A.; Bovendeerd, Peter H.M.; Davies, Peter F.; Jayaraman, Girija; Jensen, Oliver E.; Lee, Jack; Parker, Kim H.; Popel, Aleksander S.; Secomb, Timothy W.; Siebes, Maria; Sherwin, Spencer J.; Shipley, Rebecca J.; Smith, Nicolas P.; van de Vosse, Frans N.

2013-01-01

A key aim of the cardiac Physiome Project is to develop theoretical models to simulate the functional behaviour of the heart under physiological and pathophysiological conditions. Heart function is critically dependent on the delivery of an adequate blood supply to the myocardium via the coronary vasculature. Key to this critical function of the coronary vasculature is system dynamics that emerge via the interactions of the numerous constituent components at a range of spatial and temporal scales. Here, we focus on several components for which theoretical approaches can be applied, including vascular structure and mechanics, blood flow and mass transport, flow regulation, angiogenesis and vascular remodelling, and vascular cellular mechanics. For each component, we summarise the current state of the art in model development, and discuss areas requiring further research. We highlight the major challenges associated with integrating the component models to develop a computational tool that can ultimately be used to simulate the responses of the coronary vascular system to changing demands and to diseases and therapies. PMID:21040741

Weight and the Future of Space Flight Hardware Cost Modeling

NASA Technical Reports Server (NTRS)

Prince, Frank A.

2003-01-01

Weight has been used as the primary input variable for cost estimating almost as long as there have been parametric cost models. While there are good reasons for using weight, serious limitations exist. These limitations have been addressed by multi-variable equations and trend analysis in models such as NAFCOM, PRICE, and SEER; however, these models have not be able to address the significant time lags that can occur between the development of similar space flight hardware systems. These time lags make the cost analyst's job difficult because insufficient data exists to perform trend analysis, and the current set of parametric models are not well suited to accommodating process improvements in space flight hardware design, development, build and test. As a result, people of good faith can have serious disagreement over the cost for new systems. To address these shortcomings, new cost modeling approaches are needed. The most promising approach is process based (sometimes called activity) costing. Developing process based models will require a detailed understanding of the functions required to produce space flight hardware combined with innovative approaches to estimating the necessary resources. Particularly challenging will be the lack of data at the process level. One method for developing a model is to combine notional algorithms with a discrete event simulation and model changes to the total cost as perturbations to the program are introduced. Despite these challenges, the potential benefits are such that efforts should be focused on developing process based cost models.

Effects of Distance Coaching on Teachers' Use of Pyramid Model Practices: A Pilot Study

ERIC Educational Resources Information Center

Artman-Meeker, Kathleen; Hemmeter, Mary Louise; Snyder, Patricia

2014-01-01

The purpose of this pilot study was to compare the effects of 2 professional development approaches on teachers' implementation of the "Pyramid" model, a classroom-wide approach for fostering social-emotional development and addressing challenging behavior. The study had 2 goals: (a) to examine the differential effects of workshop…

Development, fabrication, and modeling of highly sensitive conjugated polymer based piezoresistive sensors in electronic skin applications

NASA Astrophysics Data System (ADS)

Khalili, Nazanin; Naguib, Hani E.; Kwon, Roy H.

2016-04-01

Human intervention can be replaced through development of tools resulted from utilizing sensing devices possessing a wide range of applications including humanoid robots or remote and minimally invasive surgeries. Similar to the five human senses, sensors interface with their surroundings to stimulate a suitable response or action. The sense of touch which arises in human skin is among the most challenging senses to emulate due to its ultra high sensitivity. This has brought forth novel challenging issues to consider in the field of biomimetic robotics. In this work, using a multiphase reaction, a polypyrrole (PPy) based hydrogel is developed as a resistive type pressure sensor with an intrinsically elastic microstructure stemming from three dimensional hollow spheres. Furthermore, a semi-analytical constriction resistance model accounting for the real contact area between the PPy hydrogel sensors and the electrode along with the dependency of the contact resistance change on the applied load is developed. The model is then solved using a Monte Carlo technique and the sensitivity of the sensor is obtained. The experimental results showed the good tracking ability of the proposed model.

Testing Scientific Software: A Systematic Literature Review

PubMed Central

Kanewala, Upulee; Bieman, James M.

2014-01-01

Context Scientific software plays an important role in critical decision making, for example making weather predictions based on climate models, and computation of evidence for research publications. Recently, scientists have had to retract publications due to errors caused by software faults. Systematic testing can identify such faults in code. Objective This study aims to identify specific challenges, proposed solutions, and unsolved problems faced when testing scientific software. Method We conducted a systematic literature survey to identify and analyze relevant literature. We identified 62 studies that provided relevant information about testing scientific software. Results We found that challenges faced when testing scientific software fall into two main categories: (1) testing challenges that occur due to characteristics of scientific software such as oracle problems and (2) testing challenges that occur due to cultural differences between scientists and the software engineering community such as viewing the code and the model that it implements as inseparable entities. In addition, we identified methods to potentially overcome these challenges and their limitations. Finally we describe unsolved challenges and how software engineering researchers and practitioners can help to overcome them. Conclusions Scientific software presents special challenges for testing. Specifically, cultural differences between scientist developers and software engineers, along with the characteristics of the scientific software make testing more difficult. Existing techniques such as code clone detection can help to improve the testing process. Software engineers should consider special challenges posed by scientific software such as oracle problems when developing testing techniques. PMID:25125798

Current Challenges in Health Economic Modeling of Cancer Therapies: A Research Inquiry

PubMed Central

Miller, Jeffrey D.; Foley, Kathleen A.; Russell, Mason W.

2014-01-01

Background The demand for economic models that evaluate cancer treatments is increasing, as healthcare decision makers struggle for ways to manage their budgets while providing the best care possible to patients with cancer. Yet, after nearly 2 decades of cultivating and refining techniques for modeling the cost-effectiveness and budget impact of cancer therapies, serious methodologic and policy challenges have emerged that question the adequacy of economic modeling as a sound decision-making tool in oncology. Objectives We sought to explore some of the contentious issues associated with the development and use of oncology economic models as informative tools in current healthcare decision-making. Our objective was to draw attention to these complex pharmacoeconomic concerns and to promote discussion within the oncology and health economics research communities. Methods Using our combined expertise in health economics research and economic modeling, we structured our inquiry around the following 4 questions: (1) Are economic models adequately addressing questions relevant to oncology decision makers; (2) What are the methodologic limitations of oncology economic models; (3) What guidelines are followed for developing oncology economic models; and (4) Is the evolution of oncology economic modeling keeping pace with treatment innovation? Within the context of each of these questions, we discuss issues related to the technical limitations of oncology modeling, the availability of adequate data for developing models, and the problems with how modeling analyses and results are presented and interpreted. Discussion There is general acceptance that economic models are good, essential tools for decision-making, but the practice of oncology and its rapidly evolving technologies present unique challenges that make assessing and demonstrating value especially complex. There is wide latitude for improvement in oncology modeling methodologies and how model results are presented and interpreted. Conclusion Complex technical and data availability issues with oncology economic modeling pose serious concerns that need to be addressed. It is our hope that this article will provide a framework to guide future discourse on this important topic. PMID:24991399

Current challenges in health economic modeling of cancer therapies: a research inquiry.

PubMed

Miller, Jeffrey D; Foley, Kathleen A; Russell, Mason W

2014-05-01

The demand for economic models that evaluate cancer treatments is increasing, as healthcare decision makers struggle for ways to manage their budgets while providing the best care possible to patients with cancer. Yet, after nearly 2 decades of cultivating and refining techniques for modeling the cost-effectiveness and budget impact of cancer therapies, serious methodologic and policy challenges have emerged that question the adequacy of economic modeling as a sound decision-making tool in oncology. We sought to explore some of the contentious issues associated with the development and use of oncology economic models as informative tools in current healthcare decision-making. Our objective was to draw attention to these complex pharmacoeconomic concerns and to promote discussion within the oncology and health economics research communities. Using our combined expertise in health economics research and economic modeling, we structured our inquiry around the following 4 questions: (1) Are economic models adequately addressing questions relevant to oncology decision makers; (2) What are the methodologic limitations of oncology economic models; (3) What guidelines are followed for developing oncology economic models; and (4) Is the evolution of oncology economic modeling keeping pace with treatment innovation? Within the context of each of these questions, we discuss issues related to the technical limitations of oncology modeling, the availability of adequate data for developing models, and the problems with how modeling analyses and results are presented and interpreted. There is general acceptance that economic models are good, essential tools for decision-making, but the practice of oncology and its rapidly evolving technologies present unique challenges that make assessing and demonstrating value especially complex. There is wide latitude for improvement in oncology modeling methodologies and how model results are presented and interpreted. Complex technical and data availability issues with oncology economic modeling pose serious concerns that need to be addressed. It is our hope that this article will provide a framework to guide future discourse on this important topic.

Using Models to Inform Policy: Insights from Modeling the Complexities of Global Polio Eradication

NASA Astrophysics Data System (ADS)

Thompson, Kimberly M.

Drawing on over 20 years of experience modeling risks in complex systems, this talk will challenge SBP participants to develop models that provide timely and useful answers to critical policy questions when decision makers need them. The talk will include reflections on the opportunities and challenges associated with developing integrated models for complex problems and communicating their results effectively. Dr. Thompson will focus the talk largely on collaborative modeling related to global polio eradication and the application of system dynamics tools. After successful global eradication of wild polioviruses, live polioviruses will still present risks that could potentially lead to paralytic polio cases. This talk will present the insights of efforts to use integrated dynamic, probabilistic risk, decision, and economic models to address critical policy questions related to managing global polio risks. Using a dynamic disease transmission model combined with probabilistic model inputs that characterize uncertainty for a stratified world to account for variability, we find that global health leaders will face some difficult choices, but that they can take actions that will manage the risks effectively. The talk will emphasize the need for true collaboration between modelers and subject matter experts, and the importance of working with decision makers as partners to ensure the development of useful models that actually get used.

Student and resident perspectives on professionalism: beliefs, challenges, and suggested teaching strategies.

PubMed

Salinas-Miranda, Abraham A; Shaffer-Hudkins, Emily J; Bradley-Klug, Kathy L; Monroe, Alicia D H

2014-05-10

The purpose of this study was to investigate the views of medical students and residents regarding the practice of professionalism, their perceived challenges, and ideas for the development of a new curriculum in medical professionalism. Data were collected from four focus groups comprised of 27 residents and medical students recruited from the University of South Florida Morsani School of Medicine and Residency Programs between January and March 2012. A questioning protocol was used to guide the focus group discussion. Data were transcribed for thematic analysis. Learners expressed beliefs regarding key attributes of professional behaviors, factors perceived to be associated with lapses of professional behavior, skills that need to be taught, and strategies to teach professionalism from the learners' perspective. Learners perceived that the values of professionalism are often disconnected from the reality evidenced in clinical training due to a myriad of personal and contextual challenges. Residents and students need help in negotiating some of the challenges to medical professionalism that are encountered in clinical settings. We recommend a learner's centered model of curriculum development in medical professionalism that takes into consideration perceived challenges and strategies for modeling and reinforcing medical professionalism.

Passive Thermal Control Challenges for Future Exploration Missions

NASA Technical Reports Server (NTRS)

Rickman, Steven L.

2004-01-01

This slide presentation reviews the importance of developing passive thermal control for the future exploration missions envisioned in President Bush's call for human exploration of the Moon and Mars. Included in the presentation is a review of the conditions that make the thermal control very challenging on the Moon and Mars. With the future miniaturization of electronics components, power density and the associated challenges of electronics heat dissipation will provide new challenges. There is a challenge for improvement in modeling and analysis of thermal control systems, and for improved facilities to support testing of thermal-vacuum systems.

Why learning and development can lead to poorer recognition memory.

PubMed

Hayes, Brett K; Heit, Evan

2004-08-01

Current models of inductive reasoning in children and adults assume a central role for categorical knowledge. A recent paper by Sloutsky and Fisher challenges this assumption, showing that children are more likely than adults to rely on perceptual similarity as a basis for induction, and introduces a more direct method for examining the representations activated during induction. This method has the potential to constrain models of induction in novel ways, although there are still important challenges.

Simulation Modeling of a Facility Layout in Operations Management Classes

ERIC Educational Resources Information Center

Yazici, Hulya Julie

2006-01-01

Teaching quantitative courses can be challenging. Similarly, layout modeling and lean production concepts can be difficult to grasp in an introductory OM (operations management) class. This article describes a simulation model developed in PROMODEL to facilitate the learning of layout modeling and lean manufacturing. Simulation allows for the…

Modeling feeding behavior of swine to detect illness

USDA-ARS?s Scientific Manuscript database

Animal well-being may be improved by detecting disruptions in feeding behavior indicative of challenged animals. The objectives of this study were to 1) develop and optimize an autoregressive model by adjusting sensitivity of the model to detect disruptions in feeding time; 2) test the model on dail...

Business Model Innovation: A Blueprint for Higher Education

ERIC Educational Resources Information Center

Flanagan, Christine

2012-01-01

Business model innovation is one of the most challenging components of 21st-century leadership. Making incremental improvements to a business model--creating new efficiencies, expanding into adjacent markets--is hard enough. Developing and experimenting with new business models that truly transform how an institution delivers value (while…

Assessing Zika virus replication and the development of Zika-specific antibodies after a mid-gestation viral challenge in guinea pigs

PubMed Central

Fernández-Alarcón, Claudia; Hernandez-Alvarado, Nelmary; Zabeli, Jason C.; Janus, Bradley C.; Putri, Dira S.; Schleiss, Mark R.

2017-01-01

Primary Zika virus (ZIKV) infections that occur during pregnancy can cause spontaneous abortion and profoundly disrupt fetal development. While the full range of developmental abnormalities associated with congenital Zika syndrome is not yet known, severe cases of the syndrome can present with microcephaly, extensive neurologic and ocular damage, and pronounced joint malformations. Animal models that accurately recapitulate congenital Zika syndrome are urgently needed for vaccine development and for the study of ZIKV pathogenesis. As guinea pigs have successfully been used to model transplacental infections by cytomegalovirus, syphilis, and Listeria monocytogenes, we sought to test whether ZIKV could productively infect guinea pigs and whether viral transmission with attendant fetal pathology would occur after a mid-gestation viral challenge. We found that guinea pig cells supported ZIKV replication in vitro. Experimental infection of non-pregnant animals did not result in overt disease but low-level, detectable viremia was observed. When pregnant guinea pigs were challenged with ZIKV at between 18 and 21 days gestational age, ZIKV was not detected in maternal or pup blood, plasma, or tissues and no significant differences in maternal weight gain or pup size were observed following challenge. Nonetheless, a robust antibody response against ZIKV was detected in both the pups and dams. These results suggest that, while guinea pigs can model aspects of the immune response to ZIKV infection during pregnancy, naturally circulating ZIKV strains are not pathogenic during the pregnancy of immunocompetent guinea pigs and do not interfere with normal pup development. PMID:29099873

A Component Approach to Collaborative Scientific Software Development: Tools and Techniques Utilized by the Quantum Chemistry Science Application Partnership

DOE PAGES

Kenny, Joseph P.; Janssen, Curtis L.; Gordon, Mark S.; ...

2008-01-01

Cutting-edge scientific computing software is complex, increasingly involving the coupling of multiple packages to combine advanced algorithms or simulations at multiple physical scales. Component-based software engineering (CBSE) has been advanced as a technique for managing this complexity, and complex component applications have been created in the quantum chemistry domain, as well as several other simulation areas, using the component model advocated by the Common Component Architecture (CCA) Forum. While programming models do indeed enable sound software engineering practices, the selection of programming model is just one building block in a comprehensive approach to large-scale collaborative development which must also addressmore » interface and data standardization, and language and package interoperability. We provide an overview of the development approach utilized within the Quantum Chemistry Science Application Partnership, identifying design challenges, describing the techniques which we have adopted to address these challenges and highlighting the advantages which the CCA approach offers for collaborative development.« less

What did the Romans ever do for us? Putting humans in global land models

NASA Astrophysics Data System (ADS)

Bierkens, M. F.; Wada, Y.; Dermody, B.; Van Beek, L. P.

2016-12-01

During the late 1980s and early 1990s, awareness of the shortage of global water resources lead to the first detailed global water resources assessments using regional statistics of water use and observations of meteorological and hydrological variables. Shortly thereafter, the first macroscale hydrological models (MHM) appeared. In these models, blue water (i.e., surface water and renewable groundwater) availability was calculated by accumulating runoff over a stream network and comparing it with population densities or with estimated water demand for agriculture, industry and households. In this talk we review the evolution of human impact modelling in global land models with a focus on global water resources, touching upon developments of the last 15 years: i.e. calculating human water scarcity; estimating groundwater depletion; adding dams and reservoirs; fully integrating water use (abstraction, application, consumption, return flow) in the hydrology; simulating the effects of land use change. We identify four major challenges that hamper the further development of integrated water resources modelling and thus prohibit realistic projections of the future terrestrial water cycle in the Anthropocene. These are: 1) including the ability to model infrastructural changes and measures; 2) projecting future water demand and water use and associated measures; 3) including virtual water trade; 4) including land use change and landscape change. While all these challenges will likely benefit from hydro-economics and the newly developing field of socio-hydrology, we also show that especially for challenges 3 and 4 lessons can be drawn from the (pre)historic past. To make this point we provide two case studies: one modelling the virtual water trade in the Roman Empire and one modelling human-landscape interaction in prehistoric Calabria (Italy).

A Tool for Investigating Asthma and COPD Exacerbations: A Newly Manufactured and Well Characterised GMP Wild-Type Human Rhinovirus for Use in the Human Viral Challenge Model

PubMed Central

Fullen, Daniel J.; Murray, Bryan; Mori, Julie; Catchpole, Andrew; Borley, Daryl W.; Murray, Edward J.; Balaratnam, Ganesh; Gilbert, Anthony; Mann, Alex; Hughes, Fiona; Lambkin-Williams, Rob

2016-01-01

Background Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose. Methods and Stock Development A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children’s Hospital, USA) was obtained with appropriate medical history and consent. We manufactured a new HRV-16 stock by minimal passage in a WI-38 cell line under Good Manufacturing Practice conditions. Having first subjected the stock to rigorous adventitious agent testing and determining the virus suitability for human use, we conducted an initial safety and pathogenicity clinical study in adult volunteers in our dedicated clinical quarantine facility in London. Human Challenge and Conclusions In this study we have demonstrated the new Wild-Type HRV-16 Challenge Virus to be both safe and pathogenic, causing an appropriate level of disease in experimentally inoculated healthy adult volunteers. Furthermore, by inoculating volunteers with a range of different inoculum titres, we have established the minimum inoculum titre required to achieve reproducible disease. We have demonstrated that although inoculation titres as low as 1 TCID50 can produce relatively high infection rates, the optimal titre for progression with future HRV challenge model development with this virus stock was 10 TCID50. Studies currently underway are evaluating the use of this virus as a challenge agent in asthmatics. Trial Registration ClinicalTrials.gov NCT02522832 PMID:27936016

Reproducible model development in the cardiac electrophysiology Web Lab.

PubMed

Daly, Aidan C; Clerx, Michael; Beattie, Kylie A; Cooper, Jonathan; Gavaghan, David J; Mirams, Gary R

2018-05-26

The modelling of the electrophysiology of cardiac cells is one of the most mature areas of systems biology. This extended concentration of research effort brings with it new challenges, foremost among which is that of choosing which of these models is most suitable for addressing a particular scientific question. In a previous paper, we presented our initial work in developing an online resource for the characterisation and comparison of electrophysiological cell models in a wide range of experimental scenarios. In that work, we described how we had developed a novel protocol language that allowed us to separate the details of the mathematical model (the majority of cardiac cell models take the form of ordinary differential equations) from the experimental protocol being simulated. We developed a fully-open online repository (which we termed the Cardiac Electrophysiology Web Lab) which allows users to store and compare the results of applying the same experimental protocol to competing models. In the current paper we describe the most recent and planned extensions of this work, focused on supporting the process of model building from experimental data. We outline the necessary work to develop a machine-readable language to describe the process of inferring parameters from wet lab datasets, and illustrate our approach through a detailed example of fitting a model of the hERG channel using experimental data. We conclude by discussing the future challenges in making further progress in this domain towards our goal of facilitating a fully reproducible approach to the development of cardiac cell models. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Engaging partners to initiate evaluation efforts: tactics used and lessons learned from the prevention research centers program.

PubMed

Wright, Demia Sundra; Anderson, Lynda A; Brownson, Ross C; Gwaltney, Margaret K; Scherer, Jennifer; Cross, Alan W; Goodman, Robert M; Schwartz, Randy; Sims, Tom; White, Carol R

2008-01-01

The Centers for Disease Control and Prevention's (CDC's) Prevention Research Centers (PRC) Program underwent a 2-year evaluation planning project using a participatory process that allowed perspectives from the national community of PRC partners to be expressed and reflected in a national logic model. The PRC Program recognized the challenge in developing a feasible, useable, and relevant evaluation process for a large, diverse program. To address the challenge, participatory and utilization-focused evaluation models were used. Four tactics guided the evaluation planning process: 1) assessing stakeholders' communication needs and existing communication mechanisms and infrastructure; 2) using existing mechanisms and establishing others as needed to inform, educate, and request feedback; 3) listening to and using feedback received; and 4) obtaining adequate resources and building flexibility into the project plan to support multifaceted mechanisms for data collection. Participatory methods resulted in buy-in from stakeholders and the development of a national logic model. Benefits included CDC's use of the logic model for program planning and development of a national evaluation protocol and increased expectations among PRC partners for involvement. Challenges included the time, effort, and investment of program resources required for the participatory approach and the identification of whom to engage and when to engage them for feedback on project decisions. By using a participatory and utilization-focused model, program partners positively influenced how CDC developed an evaluation plan. The tactics we used can guide the involvement of program stakeholders and help with decisions on appropriate methods and approaches for engaging partners.

A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses

PubMed Central

Safronetz, David; Mire, Chad; Rosenke, Kyle; Feldmann, Friederike; Haddock, Elaine; Geisbert, Thomas; Feldmann, Heinz

2015-01-01

Background Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a “universal” LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models. Methodologies/principle findings Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever. Conclusions/significance Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever. PMID:25884628

Translational research and the evolving landscape for biomedical innovation.

PubMed

Kaitin, Kenneth I

2012-10-01

This article addresses current challenges facing pharmaceutical and biopharmaceutical developers, including the expiration of patents on many high-revenue-generating products, increasing competition in the marketplace, low public support, high regulatory hurdles, and the increasing time, cost, and risk of new product development. To meet these challenges, drug developers are looking to new models of innovation to improve efficiency, lower risk, and increase output. These new models include codevelopment agreements with small companies, multicompany consortia, and strategic partnerships with academic research centers. In the United States and the European Union, the government is supporting these efforts by creating incentives for academic centers to foster translational research and become more "commercially minded". The goal for all stakeholders is to reduce the barriers to product development and bring new medicines to market in a timely and cost-efficient manner.

Applying the Deployment Focused Treatment Development Model to School-Based Yoga for Elementary School Students: Steps One and Two

ERIC Educational Resources Information Center

Smith, Bradley H.; Connington, Alison; McQuillin, Samuel; Crowder Bierman, Leigh

2014-01-01

There is growing interest in yoga to enhance positive youth development, but many challenges to overcome before introducing yoga to schools. Weisz et al. [Weisz, J. R., Jensen, A. L., McLeod, B. D. (2004). "Development and dissemination of child and adolescent therapies: milestones, methods, and a new deployment-focussed model." In E.…

Overcoming challenges of catastrophe modelling in data poor regions

NASA Astrophysics Data System (ADS)

Grassby, L.; Millinship, I.; Breinl, K.

2012-04-01

There is an increasing demand for loss accumulation tools in expanding international insurance markets such as India, China and Thailand. This reflects the combination of an increase in exposures in these territories as industry intensifies and urban development expands, as well as several notable natural catastrophes affecting these areas over the past few years (e.g. extreme floods in Mumbai in 2006 and in Thailand in 2011). Large, global insurers and reinsurers are embracing the opportunity to underwrite these exposures but only where adequate tools are available to provide understanding of the hazards, exposures and potential losses. Unlike more developed countries, data availability in these regions is typically limited and of poor resolution, but model development is still required in order to analyse the risk. Some of the modelling challenges associated with data limitations include: (1) dealing with a lack of hydrological data which results in greater uncertainty of the flow rate and event frequency; (2) lower DTM resolution than that available across much of Europe, which underlies the hazard component of the catastrophe model; (3) limited accessibility to data that characterises the Built Environment including information on different building types and their susceptibility to damage; and (4) a lack of claims data from previous events or engineering research into the vulnerability of different building types. This is used to generate of country and structure specific vulnerability curves that explain the relationship between hazard intensity and damages. By presenting an industry specific flood model for data-poor India in collaboration with Allianz Re, we illustrate how we have overcome many of these challenges to allow loss accumulations to be made. The resulting model was successfully validated against the floods in Mumbai and Surat in 2006 and is being developed further with the availability of new data.

Developing predictive insight into changing water systems: use-inspired hydrologic science for the Anthropocene

NASA Astrophysics Data System (ADS)

Thompson, S. E.; Sivapalan, M.; Harman, C. J.; Srinivasan, V.; Hipsey, M. R.; Reed, P.; Montanari, A.; Blöschl, G.

2013-12-01

Globally, many different kinds of water resources management issues call for policy- and infrastructure-based responses. Yet responsible decision-making about water resources management raises a fundamental challenge for hydrologists: making predictions about water resources on decadal- to century-long timescales. Obtaining insight into hydrologic futures over 100 yr timescales forces researchers to address internal and exogenous changes in the properties of hydrologic systems. To do this, new hydrologic research must identify, describe and model feedbacks between water and other changing, coupled environmental subsystems. These models must be constrained to yield useful insights, despite the many likely sources of uncertainty in their predictions. Chief among these uncertainties are the impacts of the increasing role of human intervention in the global water cycle - a defining challenge for hydrology in the Anthropocene. Here we present a research agenda that proposes a suite of strategies to address these challenges from the perspectives of hydrologic science research. The research agenda focuses on the development of co-evolutionary hydrologic modeling to explore coupling across systems, and to address the implications of this coupling on the long-time behavior of the coupled systems. Three research directions support the development of these models: hydrologic reconstruction, comparative hydrology and model-data learning. These strategies focus on understanding hydrologic processes and feedbacks over long timescales, across many locations, and through strategic coupling of observational and model data in specific systems. We highlight the value of use-inspired and team-based science that is motivated by real-world hydrologic problems but targets improvements in fundamental understanding to support decision-making and management. Fully realizing the potential of this approach will ultimately require detailed integration of social science and physical science understanding of water systems, and is a priority for the developing field of sociohydrology.

The paradigm shift to an "open" model in drug development.

PubMed

Au, Regina

2014-12-01

The rising cost of healthcare, the rising cost for drug development, the patent cliff for Big pharma, shorter patent protection, decrease reimbursement, and the recession have made it more difficult for the pharmaceutical and biotechnology industry to develop drugs. Due to the unsustainable amount of time and money in developing a drug that will have a significant return on investment (ROI) it has become hard to sustain a robust pipeline. The industry is transforming its business model to meet these challenges. In essence a paradigm shift is occurring; the old "closed" model is giving way to a new "open" business model.

Challenges Associated With Applying Physiologically Based Pharmacokinetic Modeling for Public Health Decision-Making

EPA Science Inventory

The development and application of physiologically based pharmacokinetic (PBPK) models in chemical toxicology have grown steadily since their emergence in the 1980s. However, critical evaluation of PBPK models to support public health decision-making across federal agencies has t...

Developing and validating risk prediction models in an individual participant data meta-analysis

PubMed Central

2014-01-01

Background Risk prediction models estimate the risk of developing future outcomes for individuals based on one or more underlying characteristics (predictors). We review how researchers develop and validate risk prediction models within an individual participant data (IPD) meta-analysis, in order to assess the feasibility and conduct of the approach. Methods A qualitative review of the aims, methodology, and reporting in 15 articles that developed a risk prediction model using IPD from multiple studies. Results The IPD approach offers many opportunities but methodological challenges exist, including: unavailability of requested IPD, missing patient data and predictors, and between-study heterogeneity in methods of measurement, outcome definitions and predictor effects. Most articles develop their model using IPD from all available studies and perform only an internal validation (on the same set of data). Ten of the 15 articles did not allow for any study differences in baseline risk (intercepts), potentially limiting their model’s applicability and performance in some populations. Only two articles used external validation (on different data), including a novel method which develops the model on all but one of the IPD studies, tests performance in the excluded study, and repeats by rotating the omitted study. Conclusions An IPD meta-analysis offers unique opportunities for risk prediction research. Researchers can make more of this by allowing separate model intercept terms for each study (population) to improve generalisability, and by using ‘internal-external cross-validation’ to simultaneously develop and validate their model. Methodological challenges can be reduced by prospectively planned collaborations that share IPD for risk prediction. PMID:24397587

Towards a Generalizable Time Expression Model for Temporal Reasoning in Clinical Notes

PubMed Central

Velupillai, Sumithra; Mowery, Danielle L.; Abdelrahman, Samir; Christensen, Lee; Chapman, Wendy W

2015-01-01

Accurate temporal identification and normalization is imperative for many biomedical and clinical tasks such as generating timelines and identifying phenotypes. A major natural language processing challenge is developing and evaluating a generalizable temporal modeling approach that performs well across corpora and institutions. Our long-term goal is to create such a model. We initiate our work on reaching this goal by focusing on temporal expression (TIMEX3) identification. We present a systematic approach to 1) generalize existing solutions for automated TIMEX3 span detection, and 2) assess similarities and differences by various instantiations of TIMEX3 models applied on separate clinical corpora. When evaluated on the 2012 i2b2 and the 2015 Clinical TempEval challenge corpora, our conclusion is that our approach is successful – we achieve competitive results for automated classification, and we identify similarities and differences in TIMEX3 modeling that will be informative in the development of a simplified, general temporal model. PMID:26958265

Model-based and Model-free Machine Learning Techniques for Diagnostic Prediction and Classification of Clinical Outcomes in Parkinson's Disease.

PubMed

Gao, Chao; Sun, Hanbo; Wang, Tuo; Tang, Ming; Bohnen, Nicolaas I; Müller, Martijn L T M; Herman, Talia; Giladi, Nir; Kalinin, Alexandr; Spino, Cathie; Dauer, William; Hausdorff, Jeffrey M; Dinov, Ivo D

2018-05-08

In this study, we apply a multidisciplinary approach to investigate falls in PD patients using clinical, demographic and neuroimaging data from two independent initiatives (University of Michigan and Tel Aviv Sourasky Medical Center). Using machine learning techniques, we construct predictive models to discriminate fallers and non-fallers. Through controlled feature selection, we identified the most salient predictors of patient falls including gait speed, Hoehn and Yahr stage, postural instability and gait difficulty-related measurements. The model-based and model-free analytical methods we employed included logistic regression, random forests, support vector machines, and XGboost. The reliability of the forecasts was assessed by internal statistical (5-fold) cross validation as well as by external out-of-bag validation. Four specific challenges were addressed in the study: Challenge 1, develop a protocol for harmonizing and aggregating complex, multisource, and multi-site Parkinson's disease data; Challenge 2, identify salient predictive features associated with specific clinical traits, e.g., patient falls; Challenge 3, forecast patient falls and evaluate the classification performance; and Challenge 4, predict tremor dominance (TD) vs. posture instability and gait difficulty (PIGD). Our findings suggest that, compared to other approaches, model-free machine learning based techniques provide a more reliable clinical outcome forecasting of falls in Parkinson's patients, for example, with a classification accuracy of about 70-80%.

Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy

PubMed Central

McGreevy, Joe W.; Hakim, Chady H.; McIntosh, Mark A.; Duan, Dongsheng

2015-01-01

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs. PMID:25740330

Advancing the management and control of typhoid fever: a review of the historical role of human challenge studies.

PubMed

Waddington, Claire S; Darton, Thomas C; Woodward, William E; Angus, Brian; Levine, Myron M; Pollard, Andrew J

2014-05-01

Typhoid infection causes considerable morbidity and mortality worldwide, particularly in settings where lack of clean water and inadequate sanitation facilitate disease spread through faecal-oral transmission. Improved understanding of the pathogenesis, immune control and microbiology of Salmonella Typhi infection can help accelerate the development of improved vaccines and diagnostic tests necessary for disease control. S. Typhi is a human-restricted pathogen; therefore animal models are limited in their relevance to human infection. During the latter half of the 20th century, induced human infection ("challenge") studies with S. Typhi were used effectively to assess quantitatively the human host response to challenge and to measure directly the efficacy of typhoid vaccines in preventing clinical illness. Here, the findings of these historic challenge studies are reviewed, highlighting the pivotal role that challenge studies have had in improving our understanding of the host-pathogen interaction, and illustrating issues relevant to modern typhoid challenge model design. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

On the role of model-based monitoring for adaptive planning under uncertainty

NASA Astrophysics Data System (ADS)

Raso, Luciano; Kwakkel, Jan; Timmermans, Jos; Haasnoot, Mariolijn

2016-04-01

Adaptive plans, designed to anticipate and respond to an unfolding uncertain future, have found a fertile application domain in the planning of deltas that are exposed to rapid socioeconomic development and climate change. Adaptive planning, under the moniker of adaptive delta management, is used in the Dutch Delta Program for developing a nation-wide plan to prepare for uncertain climate change and socio-economic developments. Scientifically, adaptive delta management relies heavily on Dynamic Adaptive Policy Pathways. Currently, in the Netherlands the focus is shifting towards implementing the adaptive delta plan. This shift is especially relevant because the efficacy of adaptive plans hinges on monitoring on-going developments and ensuring that actions are indeed taken if and when necessary. In the design of an effective monitoring system for an adaptive plan, three challenges have to be confronted: • Shadow of the past: The development of adaptive plans and the design of their monitoring system relies heavily on current knowledge of the system, and current beliefs about plausible future developments. A static monitoring system is therefore exposed to the exact same uncertainties one tries to address through adaptive planning. • Inhibition of learning: Recent applications of adaptive planning tend to overlook the importance of learning and new information, and fail to account for this explicitly in the design of adaptive plans. • Challenge of surprise: Adaptive policies are designed in light of the current foreseen uncertainties. However, developments that are not considered during the design phase as being plausible could still substantially affect the performance of adaptive policies. The shadow of the past, the inhibition of learning, and the challenge of surprise taken together suggest that there is a need for redesigning the concepts of monitoring and evaluation to support the implementation of adaptive plans. Innovations from control theory, triggered by the challenge of uncertainty in operational control, may offer solutions from which monitoring for adaptive planning can benefit. Specifically: (i) in control, observations are incorporated into the model through data assimilation, updating the present state, boundary conditions, and parameters based on new observations, diminishing the shadow of the past; (ii) adaptive control is a way to modify the characteristics of the internal model, incorporating new knowledge on the system, countervailing the inhibition of learning; and (iii) in closed-loop control, a continuous system update equips the controller with "inherent robustness", i.e. to capacity to adapts to new conditions even when these were not initially considered. We aim to explore how inherent robustness addresses the challenge of surprise. Innovations in model-based control might help to improve and adapt the models used to support adaptive delta management to new information (reducing uncertainty). Moreover, this would offer a starting point for using these models not only in the design of adaptive plans, but also as part of the monitoring. The proposed research requires multidisciplinary cooperation between control theory, the policy sciences, and integrated assessment modeling.

Early career professional development issues for military academic psychiatrists.

PubMed

Warner, Christopher H; Bobo, William V; Flynn, Julianne

2005-01-01

Academically motivated graduates of military psychiatric residency programs confront serious challenges. In this article, the authors present a junior faculty development model organized around four overlapping domains: mentorship, scholarship, research, and career planning/development. Using these four domains as a platform for discussion, the authors focus on challenges facing academically oriented early-career military psychiatrists and provide guidance. The authors believe that a proactive stance, skillful mentoring, self-awareness through conscious planning and effort, ability to capitalize on existing opportunities for growth, and attention to detail are all vital to the junior military psychiatrist.

Technology Investments in the NASA Entry Systems Modeling Project

NASA Technical Reports Server (NTRS)

Barnhardt, Michael; Wright, Michael; Hughes, Monica

2017-01-01

The Entry Systems Modeling (ESM) technology development project, initiated in 2012 under NASAs Game Changing Development (GCD) Program, is engaged in maturation of fundamental research developing aerosciences, materials, and integrated systems products for entry, descent, and landing(EDL)technologies [1]. To date, the ESM project has published over 200 papers in these areas, comprising the bulk of NASAs research program for EDL modeling. This presentation will provide an overview of the projects successes and challenges, and an assessment of future investments in EDL modeling and simulation relevant to NASAs mission

A novel porcine model of ventilator-associated pneumonia caused by oropharyngeal challenge with Pseudomonas aeruginosa.

PubMed

Li Bassi, Gianluigi; Rigol, Montserrat; Marti, Joan-Daniel; Saucedo, Lina; Ranzani, Otavio T; Roca, Ignasi; Cabanas, Maria; Muñoz, Laura; Giunta, Valeria; Luque, Nestor; Rinaudo, Mariano; Esperatti, Mariano; Fernandez-Barat, Laia; Ferrer, Miquel; Vila, Jordi; Ramirez, Jose; Torres, Antoni

2014-05-01

Animal models of ventilator-associated pneumonia (VAP) in primates, sheep, and pigs differ in the underlying pulmonary injury, etiology, bacterial inoculation methods, and time to onset. The most common ovine and porcine models do not reproduce the primary pathogenic mechanism of the disease, through the aspiration of oropharyngeal pathogens, or the most prevalent human etiology. Herein the authors characterize a novel porcine model of VAP due to aspiration of oropharyngeal secretions colonized by Pseudomonas aeruginosa. Ten healthy pigs were intubated, positioned in anti-Trendelenburg, and mechanically ventilated for 72 h. Three animals did not receive bacterial challenge, whereas in seven animals, a P. aeruginosa suspension was instilled into the oropharynx. Tracheal aspirates were cultured and respiratory mechanics were recorded. On autopsy, lobar samples were obtained to corroborate VAP through microbiological and histological studies. In animals not challenged, diverse bacterial colonization of the airways was found and monolobar VAP rarely developed. In animals with P. aeruginosa challenge, colonization of tracheal secretion increased up to 6.39 ± 0.34 log colony-forming unit (cfu)/ml (P < 0.001). VAP was confirmed in six of seven pigs, in 78% of the cases developed in the dependent lung segments (right medium and lower lobes, P = 0.032). The static respiratory system elastance worsened to 41.5 ± 5.8 cm H2O/l (P = 0.001). The authors devised a VAP model caused by aspiration of oropharyngeal P. aeruginosa, a frequent causative pathogen of human VAP. The model also overcomes the practical and legislative limitations associated with the use of primates. The authors' model could be employed to study pathophysiologic mechanisms, as well as novel diagnostic/preventive strategies.

Computational Aspects of Data Assimilation and the ESMF

NASA Technical Reports Server (NTRS)

daSilva, A.

2003-01-01

The scientific challenge of developing advanced data assimilation applications is a daunting task. Independently developed components may have incompatible interfaces or may be written in different computer languages. The high-performance computer (HPC) platforms required by numerically intensive Earth system applications are complex, varied, rapidly evolving and multi-part systems themselves. Since the market for high-end platforms is relatively small, there is little robust middleware available to buffer the modeler from the difficulties of HPC programming. To complicate matters further, the collaborations required to develop large Earth system applications often span initiatives, institutions and agencies, involve geoscience, software engineering, and computer science communities, and cross national borders.The Earth System Modeling Framework (ESMF) project is a concerted response to these challenges. Its goal is to increase software reuse, interoperability, ease of use and performance in Earth system models through the use of a common software framework, developed in an open manner by leaders in the modeling community. The ESMF addresses the technical and to some extent the cultural - aspects of Earth system modeling, laying the groundwork for addressing the more difficult scientific aspects, such as the physical compatibility of components, in the future. In this talk we will discuss the general philosophy and architecture of the ESMF, focussing on those capabilities useful for developing advanced data assimilation applications.

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

Phillips, Claire L.; Bond-Lamberty, Ben; Desai, Ankur R.

A recent acceleration of model-data synthesis activities has leveraged many terrestrial carbon (C) datasets, but utilization of soil respiration (RS) data has not kept pace with other types such as eddy covariance (EC) fluxes and soil C stocks. Here we argue that RS data, including non-continuous measurements from survey sampling campaigns, have unrealized value and should be utilized more extensively and creatively in data synthesis and modeling activities. We identify three major challenges in interpreting RS data, and discuss opportunities to address them. The first challenge is that when RS is compared to ecosystem respiration (RECO) measured from EC towers,more » it is not uncommon to find substantial mismatch, indicating one or both flux methodologies are unreliable. We argue the most likely cause of mismatch is unreliable EC data, and there is an unrecognized opportunity to utilize RS for EC quality control. The second challenge is that RS integrates belowground heterotrophic (RH) and autotrophic (RA) activity, whereas modelers generally prefer partitioned fluxes, and few models include an explicit RS output. Opportunities exist to use the total RS flux for data assimilation and model benchmarking methods rather than less-certain partitioned fluxes. Pushing for more experiments that not only partition RS but also monitor the age of RA and RH, as well as for the development of belowground RA components in models, would allow for more direct comparison between measured and modeled values. The third challenge is that soil respiration is generally measured at a very different resolution than that needed for comparison to EC or ecosystem- to global-scale models. Measuring soil fluxes with finer spatial resolution and more extensive coverage, and downscaling EC fluxes to match the scale of RS, will improve chamber and tower comparisons. Opportunities also exist to estimate RH at regional scales by implementing decomposition functional types, akin to plant functional types. We conclude by discussing the benefits that wide use of RS data will bring to model development, and database developments that will make RS data more robust, useful, and broadly available to the research community.« less

Developing Cognitive Models for Social Simulation from Survey Data

NASA Astrophysics Data System (ADS)

Alt, Jonathan K.; Lieberman, Stephen

The representation of human behavior and cognition continues to challenge the modeling and simulation community. The use of survey and polling instruments to inform belief states, issue stances and action choice models provides a compelling means of developing models and simulations with empirical data. Using these types of data to population social simulations can greatly enhance the feasibility of validation efforts, the reusability of social and behavioral modeling frameworks, and the testable reliability of simulations. We provide a case study demonstrating these effects, document the use of survey data to develop cognitive models, and suggest future paths forward for social and behavioral modeling.

The Future of Water Security in Metropolitan Region of Sao Paulo Through Different Climate Scenarios

NASA Astrophysics Data System (ADS)

Gesualdo, G. C.; Oliveira, P. T. S.; Rodrigues, D. B. B.

2017-12-01

Achieving a balance between water availability and demand is one of the most pressing environmental challenges in the twenty-first century. This challenge is exacerbated by, climate change, which has already affected the water balance of landscapes globally by intensifying runoff, reducing snowpacks, and shifting precipitation regimes. Understanding these changes is crucial to identifying future water availability and developing sustainable management plans, especially in developing countries. Here, we address the developing country water balance challenge by assessing the influence of climate change on the water availability in the Jaguari basin, Southeastern Brazil. The Jaguari basin is one of the main sources of freshwater for 9 million people in the Metropolitan Region of São Paulo. This region represents about 7% of the Brazil's Gross Domestic Product. The critical importance of the water balance challenge in this area has been highlighted recently when a major drought in southeastern Brazil revealed the vulnerability of current water management systems. Still today, the per capita water availability in the region remains severely limited. To help address this water balance challenge, we use a modeling approach to predict future water vulnerabilities of this region under different climate scenarios. Here, we calibrated and validated a lumped conceptual model using HYMOD to evaluate future scenarios using downscaled climate models resulting from HadGEM2-ES and MIROC5 GCMs forced by RCP4.5 and RCP8.5 scenarios. We also present future directions which include bias correction from long-term weather station data and an empirical uncertainty assessment. Our results provide an important overview of climate change impacts on streamflow and future water availability in the Jaguari basin, which can be used to guide the basin`s water security plans and strategies.

The kinetics of thermal generation of flavour.

PubMed

Parker, Jane K

2013-01-01

Control and optimisation of flavour is the ultimate challenge for the food and flavour industry. The major route to flavour formation during thermal processing is the Maillard reaction, which is a complex cascade of interdependent reactions initiated by the reaction between a reducing sugar and an amino compound. The complexity of the reaction means that researchers turn to kinetic modelling in order to understand the control points of the reaction and to manipulate the flavour profile. Studies of the kinetics of flavour formation have developed over the past 30 years from single- response empirical models of binary aqueous systems to sophisticated multi-response models in food matrices, based on the underlying chemistry, with the power to predict the formation of some key aroma compounds. This paper discusses in detail the development of kinetic models of thermal generation of flavour and looks at the challenges involved in predicting flavour. Copyright © 2012 Society of Chemical Industry.

Curricular Innovation for Sustainability: The Piedmont/Ponderosa Model of Faculty Development

ERIC Educational Resources Information Center

Barlett, Peggy F.; Chase, Geoffrey W.

2012-01-01

Curricular innovation is at the center of the challenges many colleges and universities face as they seek to help students address more successfully than previous generations the complex, multi-faceted, systemic challenges of global climate change, population growth, loss of biodiversity, environmental justice, toxic wastes, and food insecurity.…

Implementing Competency-Based Education: Challenges, Strategies, and a Decision-Making Framework

ERIC Educational Resources Information Center

Dragoo, Amie; Barrows, Richard

2016-01-01

The number of competency-based education (CBE) degree programs has increased rapidly over the past five years, yet there is little research on CBE program development. This study utilized conceptual models of higher education change and a qualitative methodology to analyze the strategies and challenges in implementing CBE business degree programs…

Future Orientation in Times of Threat and Challenge: How Resilient Adolescents Construct Their Future

ERIC Educational Resources Information Center

Seginer, Rachel

2008-01-01

Drawing on the importance of future orientation for adolescent development this analysis presents a model describing how future orientation is affected by high challenge (or resilience) in the face of political violence. The analysis consists of three parts. The first two present future orientation conceptualization and the psychological processes…

The effects of dexamethasone administration and E. bovis challenge on fecal oocyst count and immune function in weaned beef calves

USDA-ARS?s Scientific Manuscript database

Stressful events are believed to predispose beef calves to clinical coccidiosis. Previous studies aimed at reproducing stress-induced coccidiosis have been unsuccessful. No study has simultaneously subjected calves to stress and Eimeria challenge. Our initial goal was to develop a model of stress...

Faculty practice in a small liberal arts college.

PubMed

Speziale, H J

2001-01-01

Small liberal arts colleges are challenged to find ways to participate in faculty practice. With limited access to large healthcare centers, small liberal arts colleges must create innovative faculty practice models. The author shares one college's experience in faculty practice that can be used by others, detailing practice development, funding, developmental challenges, and future goals.

Exploring the Visuospatial Challenge of Learning about Day and Night and the Sun's Path

ERIC Educational Resources Information Center

Heywood, David; Parker, Joan; Rowlands, Mark

2013-01-01

The role of visualization and model-based reasoning has become increasingly significant in science education across a range of contexts. It is generally recognized that supporting learning in developing causal explanations for observed astronomical events presents considerable pedagogic challenge. Understanding the Sun's apparent movement…

Challenges in Transdisciplinary, Integrated Projects: Reflections on the Case of Faculty Members' Failure to Collaborate

ERIC Educational Resources Information Center

Vanasupa, Linda; McCormick, Kathryn E.; Stefanco, Carolyn J.; Herter, Roberta J.; McDonald, Margot

2012-01-01

In this article we describe the challenges of transdisciplinary teamwork involving four faculty members from dissimilar epistemological traditions in the process of developing a manuscript on the lessons learned in our teaching collaboration. Our difficulty originated in implicit mental models and assumptions that caused incongruence between our…

The Better Boat Challenge

ERIC Educational Resources Information Center

Schomburg, Aaron

2008-01-01

"On your mark, get set, go!" Elementary students love to hear these words as they participate in the annual Third Grade Better Boat Challenge. This highly motivational project started a few years ago as the author was developing the third-grade science curriculum to include a study that revolved around models, design, and problem solving. It has…

US EPA - A*Star Partnership - Accelerating the Acceptance of Next-Generation Sciences and Their Application to Regulatory Risk Assessment (A*Star Symposium, Singapore)

EPA Science Inventory

The path for incorporating new alternative methods and technologies into quantitative chemical risk assessment poses a diverse set of scientific challenges. Some of these challenges include development of relevant and predictive test systems and computational models to integrate...

Advantages and Challenges of Using Physics Curricula as a Model for Reforming an Undergraduate Biology Course

PubMed Central

Donovan, D. A.; Atkins, L. J.; Salter, I. Y.; Gallagher, D. J.; Kratz, R. F.; Rousseau, J. V.; Nelson, G. D.

2013-01-01

We report on the development of a life sciences curriculum, targeted to undergraduate students, which was modeled after a commercially available physics curriculum and based on aspects of how people learn. Our paper describes the collaborative development process and necessary modifications required to apply a physics pedagogical model in a life sciences context. While some approaches were easily adapted, others provided significant challenges. Among these challenges were: representations of energy, introducing definitions, the placement of Scientists’ Ideas, and the replicability of data. In modifying the curriculum to address these challenges, we have come to see them as speaking to deeper differences between the disciplines, namely that introductory physics—for example, Newton's laws, magnetism, light—is a science of pairwise interaction, while introductory biology—for example, photosynthesis, evolution, cycling of matter in ecosystems—is a science of linked processes, and we suggest that this is how the two disciplines are presented in introductory classes. We illustrate this tension through an analysis of our adaptations of the physics curriculum for instruction on the cycling of matter and energy; we show that modifications of the physics curriculum to address the biological framework promotes strong gains in student understanding of these topics, as evidenced by analysis of student work. PMID:23737629

Advantages and challenges of using physics curricula as a model for reforming an undergraduate biology course.

PubMed

Donovan, D A; Atkins, L J; Salter, I Y; Gallagher, D J; Kratz, R F; Rousseau, J V; Nelson, G D

2013-06-01

We report on the development of a life sciences curriculum, targeted to undergraduate students, which was modeled after a commercially available physics curriculum and based on aspects of how people learn. Our paper describes the collaborative development process and necessary modifications required to apply a physics pedagogical model in a life sciences context. While some approaches were easily adapted, others provided significant challenges. Among these challenges were: representations of energy, introducing definitions, the placement of Scientists' Ideas, and the replicability of data. In modifying the curriculum to address these challenges, we have come to see them as speaking to deeper differences between the disciplines, namely that introductory physics--for example, Newton's laws, magnetism, light--is a science of pairwise interaction, while introductory biology--for example, photosynthesis, evolution, cycling of matter in ecosystems--is a science of linked processes, and we suggest that this is how the two disciplines are presented in introductory classes. We illustrate this tension through an analysis of our adaptations of the physics curriculum for instruction on the cycling of matter and energy; we show that modifications of the physics curriculum to address the biological framework promotes strong gains in student understanding of these topics, as evidenced by analysis of student work.

Challenge Pools of Hepatitis C Virus Genotypes 1–6 Prototype Strains: Replication Fitness and Pathogenicity in Chimpanzees and Human Liver–Chimeric Mouse Models

PubMed Central

Bukh, Jens; Meuleman, Philip; Tellier, Raymond; Engle, Ronald E.; Feinstone, Stephen M.; Eder, Gerald; Satterfield, William C.; Govindarajan, Sugantha; Krawczynski, Krzysztof; Miller, Roger H.; Leroux-Roels, Geert; Purcell, Robert H.

2010-01-01

Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1–6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >104.7 IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 103–105 chimpanzee infectious doses/mL. Human liver–chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1–6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo. PMID:20353362

Fundamental Challenges for Modeling Electrochemical Energy Storage Systems at the Atomic Scale.

PubMed

Groß, Axel

2018-04-23

There is a strong need to improve the efficiency of electrochemical energy storage, but progress is hampered by significant technological and scientific challenges. This review describes the potential contribution of atomic-scale modeling to the development of more efficient batteries, with a particular focus on first-principles electronic structure calculations. Numerical and theoretical obstacles are discussed, along with ways to overcome them, and some recent examples are presented illustrating the insights into electrochemical energy storage that can be gained from quantum chemical studies.

Modeling nanomaterial environmental fate in aquatic systems.

PubMed

Dale, Amy L; Casman, Elizabeth A; Lowry, Gregory V; Lead, Jamie R; Viparelli, Enrica; Baalousha, Mohammed

2015-03-03

Mathematical models improve our fundamental understanding of the environmental behavior, fate, and transport of engineered nanomaterials (NMs, chemical substances or materials roughly 1-100 nm in size) and facilitate risk assessment and management activities. Although today's large-scale environmental fate models for NMs are a considerable improvement over early efforts, a gap still remains between the experimental research performed to date on the environmental fate of NMs and its incorporation into models. This article provides an introduction to the current state of the science in modeling the fate and behavior of NMs in aquatic environments. We address the strengths and weaknesses of existing fate models, identify the challenges facing researchers in developing and validating these models, and offer a perspective on how these challenges can be addressed through the combined efforts of modelers and experimentalists.

School Innovation in Science: A Model for Supporting School and Teacher Development

ERIC Educational Resources Information Center

Tytler, Russell

2007-01-01

"School Innovation in Science" represents a model, developed through working with more than 200 Victorian schools, to improve science teaching and learning. SIS works at the level of the science team and the teacher, providing resources to challenge and support the change process. Its emphasis is on strategic planning supported by a…

Professional Development for Secondary School Mathematics Teachers: A Peer Mentoring Model

ERIC Educational Resources Information Center

Kensington-Miller, Barbara

2012-01-01

Professional development is important for all teachers, and in low socio-economic schools where the challenges of teaching are greater this need is crucial. A model involving a combination of one-on-one peer mentoring integrated with group peer mentoring was piloted with experienced mathematics teachers of senior students in low socio-economic…

Analysis, modeling, and simulation (AMS) testbed development and evaluation to support dynamic mobility applications (DMA) and active transportation and demand management (ATDM) programs — gaps, challenges and future research.

DOT National Transportation Integrated Search

2017-05-01

The primary objective of AMS project is to develop multiple simulation Testbeds/transportation models to evaluate the impacts of DMA connected vehicle applications and the active and dynamic transportation management (ATDM) strategies. Through this p...

Professional Development Design Considerations in Climate Change Education: Teacher Enactment and Student Learning

ERIC Educational Resources Information Center

Drewes, Andrea; Henderson, Joseph; Mouza, Chrystalla

2018-01-01

Climate change is one of the most pressing challenges facing society, and climate change educational models are emerging in response. This study investigates the implementation and enactment of a climate change professional development (PD) model for science educators and its impact on student learning. Using an intrinsic case study methodology,…

Women's Later Life Career Development: Looking through the Lens of the Kaleidoscope Career Model

ERIC Educational Resources Information Center

August, Rachel A.

2011-01-01

This study explores the relevance of the Kaleidoscope Career Model (KCM) to women's later life career development. Qualitative interview data were gathered from 14 women in both the "truly" late career and bridge employment periods using a longitudinal design. The relevance of authenticity, balance, and challenge--central parameters in the KCM--is…

Development of a Pedagogical Model to Help Engineering Faculty Design Interdisciplinary Curricula

ERIC Educational Resources Information Center

Navarro, Maria; Foutz, Timothy; Thompson, Sidney; Singer, Kerri Patrick

2016-01-01

The purpose of this study was to develop a model to help engineering faculty overcome the challenges they face when asked to design and implement interdisciplinary curricula. Researchers at a U.S. University worked with an Interdisciplinary Consultant Team and prepared a steering document with Guiding Principles and Essential Elements for the…

Leadership Development in Higher Education: Exploring Model Impact among Students and Alumni

ERIC Educational Resources Information Center

Bommarito, Michael S.

2012-01-01

The purpose of this study was to investigate the impact of an institution-wide leadership development model on students at a private Christian university. The university being studied in this research made a significant commitment to the principles of servant-leadership as well as Kouzes and Posner's (2002) Leadership Challenge development…

Impact of Telecentre Tools on Wellbeing and Community: A Case Study and Conceptual Model of the Malian Experience

ERIC Educational Resources Information Center

Glander-Dolo, S. Mackenzie

2010-01-01

This case study of Malian technology implementation questions the historic patron-client approach of international development planning and deployment of aid and assistance to least developed countries while addressing the added challenges that globalization brings. Using a systems lens and analogy, a conceptual model is built from a literature…

A Computational Approach for Probabilistic Analysis of LS-DYNA Water Impact Simulations

NASA Technical Reports Server (NTRS)

Horta, Lucas G.; Mason, Brian H.; Lyle, Karen H.

2010-01-01

NASA s development of new concepts for the Crew Exploration Vehicle Orion presents many similar challenges to those worked in the sixties during the Apollo program. However, with improved modeling capabilities, new challenges arise. For example, the use of the commercial code LS-DYNA, although widely used and accepted in the technical community, often involves high-dimensional, time consuming, and computationally intensive simulations. Because of the computational cost, these tools are often used to evaluate specific conditions and rarely used for statistical analysis. The challenge is to capture what is learned from a limited number of LS-DYNA simulations to develop models that allow users to conduct interpolation of solutions at a fraction of the computational time. For this problem, response surface models are used to predict the system time responses to a water landing as a function of capsule speed, direction, attitude, water speed, and water direction. Furthermore, these models can also be used to ascertain the adequacy of the design in terms of probability measures. This paper presents a description of the LS-DYNA model, a brief summary of the response surface techniques, the analysis of variance approach used in the sensitivity studies, equations used to estimate impact parameters, results showing conditions that might cause injuries, and concluding remarks.

Why the elderly could bankrupt Canada and how demographic imperatives will force the redesign of acute care service delivery.

PubMed

Sinha, Samir K

2011-01-01

Canada's aging population poses a significant challenge for the existing healthcare system. While individuals 65 and older accounted for 13.7% of the population in 2005, they accounted for 60% of all acute care service spending. This paper further illustrates how the heterogeneity of the older population and its impact on patterns of healthcare use demonstrate the failings of our current care systems. Our outdated acute care models frequently disadvantage the system's highest users, who are often characterized by factors such as poly-morbidity, functional impairment and social frailty. Understanding how implementing innovative models that challenge deeply ingrained ways of providing care has proven to be a significant challenge, this paper highlights one hospital's mission to transform current traditional paradigms of care by developing and implementing an elder-friendly hospital integrated service delivery model. This hospital aims to demonstrate wide-ranging benefits of this model that can contribute toward optimizing the outcomes of hospitalization for older adults and the system as a whole. The establishment of a national agency that could support the development of a national aging strategy to promote best practice dissemination and implementation could also ensure that the significant health, social and economic benefits that better care models can realize could be more easily achieved.

Modelling impacts of climate change on arable crop diseases: progress, challenges and applications.

PubMed

Newbery, Fay; Qi, Aiming; Fitt, Bruce Dl

2016-08-01

Combining climate change, crop growth and crop disease models to predict impacts of climate change on crop diseases can guide planning of climate change adaptation strategies to ensure future food security. This review summarises recent developments in modelling climate change impacts on crop diseases, emphasises some major challenges and highlights recent trends. The use of multi-model ensembles in climate change modelling and crop modelling is contributing towards measures of uncertainty in climate change impact projections but other aspects of uncertainty remain largely unexplored. Impact assessments are still concentrated on few crops and few diseases but are beginning to investigate arable crop disease dynamics at the landscape level. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Queensland Youth Cancer Service: A Partnership Model to Facilitate Access to Quality Care for Young People Diagnosed with Cancer.

PubMed

Bradford, Natalie K; Henney, Roslyn; Walker, Rick; Walpole, Euan; Kennedy, Glen; Nicholls, Wayne; Pinkerton, Ross

2018-06-01

Global recognition of the need to improve outcomes for adolescents and young adults (AYA) with cancer has led to the development of specific oncology programs and services. In Australia, Youth Cancer Services (YCS) are now established across the country. While each service has been shaped by nationally agreed principles, program development has been influenced by local policy and geographic differences. Queensland is a vast state with a widely dispersed population; coordination of cancer services for young people across this landscape presents unique challenges. The Queensland YCS (QYCS) work in a consultative partnership model with primary treating teams, across both pediatric and adult tertiary cancer services. Understanding how cancer services approach challenges and service development can provide guidance for other developing services. In this article, we describe the goals and development of QYCS and review the outcomes achieved in the service to date. We reviewed referral data and retrieved statewide clinical activity from the web-based data system. We compared these data with cancer registry data to identify disparities and areas for service development. While the service has achieved notable outcomes, challenges remain. These include recruitment of appropriately skilled and trained health professionals for this newly developing area of oncology. In addition, there is an ongoing need to advocate for this relatively small patient group, and to promote awareness and understanding of the need for AYA-specific services. With the dispersed population and concentration of services in metropolitan Brisbane, identifying and testing new innovative models, including telehealth, to reach all AYA diagnosed with cancer regardless of location of care are priorities.

SUITABILITY OF USING IN VITRO AND COMPUTATIONALLY ESTIMATED PARAMETERS IN SIMPLIFIED PHARMACOKINETIC MODELS

EPA Science Inventory

A challenge in PBPK model development is estimating the parameters for absorption, distribution, metabolism, and excretion of the parent compound and metabolites of interest. One approach to reduce the number of parameters has been to simplify pharmacokinetic models by lumping p...

Identification of Putative Cardiovascular System Developmental Toxicants using a Classification Model based on Signaling Pathway-Adverse Outcome Pathways

EPA Science Inventory

An important challenge for an integrative approach to developmental systems toxicology is associating putative molecular initiating events (MIEs), cell signaling pathways, cell function and modeled fetal exposure kinetics. We have developed a chemical classification model based o...

Steering operational synergies in terrestrial observation networks: opportunity for advancing Earth system dynamics modelling

NASA Astrophysics Data System (ADS)

Baatz, Roland; Sullivan, Pamela L.; Li, Li; Weintraub, Samantha R.; Loescher, Henry W.; Mirtl, Michael; Groffman, Peter M.; Wall, Diana H.; Young, Michael; White, Tim; Wen, Hang; Zacharias, Steffen; Kühn, Ingolf; Tang, Jianwu; Gaillardet, Jérôme; Braud, Isabelle; Flores, Alejandro N.; Kumar, Praveen; Lin, Henry; Ghezzehei, Teamrat; Jones, Julia; Gholz, Henry L.; Vereecken, Harry; Van Looy, Kris

2018-05-01

Advancing our understanding of Earth system dynamics (ESD) depends on the development of models and other analytical tools that apply physical, biological, and chemical data. This ambition to increase understanding and develop models of ESD based on site observations was the stimulus for creating the networks of Long-Term Ecological Research (LTER), Critical Zone Observatories (CZOs), and others. We organized a survey, the results of which identified pressing gaps in data availability from these networks, in particular for the future development and evaluation of models that represent ESD processes, and provide insights for improvement in both data collection and model integration. From this survey overview of data applications in the context of LTER and CZO research, we identified three challenges: (1) widen application of terrestrial observation network data in Earth system modelling, (2) develop integrated Earth system models that incorporate process representation and data of multiple disciplines, and (3) identify complementarity in measured variables and spatial extent, and promoting synergies in the existing observational networks. These challenges lead to perspectives and recommendations for an improved dialogue between the observation networks and the ESD modelling community, including co-location of sites in the existing networks and further formalizing these recommendations among these communities. Developing these synergies will enable cross-site and cross-network comparison and synthesis studies, which will help produce insights around organizing principles, classifications, and general rules of coupling processes with environmental conditions.

A Teacher Accountability Model for Overcoming Self-Exclusion of Pupils

ERIC Educational Resources Information Center

Jamal, Abu-Hussain; Tilchin, Oleg; Essawi, Mohammad

2015-01-01

Self-exclusion of pupils is one of the prominent challenges of education. In this paper we propose the TERA model, which shapes the process of creating formative accountability of teachers to overcome the self-exclusion of pupils. Development of the model includes elaboration and integration of interconnected model components. The TERA model…

Insights into mortality patterns and causes of death through a process point of view model.

PubMed

Anderson, James J; Li, Ting; Sharrow, David J

2017-02-01

Process point of view (POV) models of mortality, such as the Strehler-Mildvan and stochastic vitality models, represent death in terms of the loss of survival capacity through challenges and dissipation. Drawing on hallmarks of aging, we link these concepts to candidate biological mechanisms through a framework that defines death as challenges to vitality where distal factors defined the age-evolution of vitality and proximal factors define the probability distribution of challenges. To illustrate the process POV, we hypothesize that the immune system is a mortality nexus, characterized by two vitality streams: increasing vitality representing immune system development and immunosenescence representing vitality dissipation. Proximal challenges define three mortality partitions: juvenile and adult extrinsic mortalities and intrinsic adult mortality. Model parameters, generated from Swedish mortality data (1751-2010), exhibit biologically meaningful correspondences to economic, health and cause-of-death patterns. The model characterizes the twentieth century epidemiological transition mainly as a reduction in extrinsic mortality resulting from a shift from high magnitude disease challenges on individuals at all vitality levels to low magnitude stress challenges on low vitality individuals. Of secondary importance, intrinsic mortality was described by a gradual reduction in the rate of loss of vitality presumably resulting from reduction in the rate of immunosenescence. Extensions and limitations of a distal/proximal framework for characterizing more explicit causes of death, e.g. the young adult mortality hump or cancer in old age are discussed.

Insights into mortality patterns and causes of death through a process point of view model

PubMed Central

Anderson, James J.; Li, Ting; Sharrow, David J.

2016-01-01

Process point of view models of mortality, such as the Strehler-Mildvan and stochastic vitality models, represent death in terms of the loss of survival capacity through challenges and dissipation. Drawing on hallmarks of aging, we link these concepts to candidate biological mechanisms through a framework that defines death as challenges to vitality where distal factors defined the age-evolution of vitality and proximal factors define the probability distribution of challenges. To illustrate the process point of view, we hypothesize that the immune system is a mortality nexus, characterized by two vitality streams: increasing vitality representing immune system development and immunosenescence representing vitality dissipation. Proximal challenges define three mortality partitions: juvenile and adult extrinsic mortalities and intrinsic adult mortality. Model parameters, generated from Swedish mortality data (1751-2010), exhibit biologically meaningful correspondences to economic, health and cause-of-death patterns. The model characterizes the 20th century epidemiological transition mainly as a reduction in extrinsic mortality resulting from a shift from high magnitude disease challenges on individuals at all vitality levels to low magnitude stress challenges on low vitality individuals. Of secondary importance, intrinsic mortality was described by a gradual reduction in the rate of loss of vitality presumably resulting from reduction in the rate of immunosenescence. Extensions and limitations of a distal/proximal framework for characterizing more explicit causes of death, e.g. the young adult mortality hump or cancer in old age are discussed. PMID:27885527

Lorcaserin: drug profile and illustrative model of the regulatory challenges of weight-loss drug development.

PubMed

Bays, Harold E

2011-03-01

Lorcaserin is a selective 5-hydroxytryptamine receptor 2c agonist developed as a weight-loss drug. Phase II and III clinical trials support lorcaserin as not only reducing adiposity (i.e., fat mass), but also as improving the metabolic diseases commonly associated with adiposopathy (i.e., fat dysfunction). At the time of this writing, regulatory processes continue towards evaluating lorcaserin as a potentially marketed weight-loss and weight-maintenance agent. Some of the challenges facing lorcaserin are similar to the difficulties encountered by all investigational weight-loss therapeutic agents, which include evolving paths towards approval. While important for clinicians to understand approval hurdles for all therapeutics, it is especially critical for researchers and developers to grasp the unique regulatory complexities of anti-obesity agents. This article profiles lorcaserin as an illustrative example of general drug development regulatory processes, and specifically details the unique challenge of weight-loss drug development.

Developing predictive insight into changing water systems: use-inspired hydrologic science for the Anthropocene

NASA Astrophysics Data System (ADS)

Thompson, S. E.; Sivapalan, M.; Harman, C. J.; Srinivasan, V.; Hipsey, M. R.; Reed, P.; Montanari, A.; Blöschl, G.

2013-06-01

Globally, many different kinds of water resources management issues call for policy and infrastructure based responses. Yet responsible decision making about water resources management raises a fundamental challenge for hydrologists: making predictions about water resources on decadal-to-century long timescales. Obtaining insight into hydrologic futures over 100 yr timescales forces researchers to address internal and exogenous changes in the properties of hydrologic systems. To do this, new hydrologic research must identify, describe and model feedbacks between water and other changing, coupled environmental subsystems. These models must be constrained to yield useful insights, despite the many likely sources of uncertainty in their predictions. Chief among these uncertainties are the impacts of the increasing role of human intervention in the global water cycle - a defining challenge for hydrology in the Anthropocene. Here we present a research agenda that proposes a suite of strategies to address these challenges. The research agenda focuses on the development of co-evolutionary hydrologic modeling to explore coupling across systems, and to address the implications of this coupling on the long-time behavior of the coupled systems. Three research directions support the development of these models: hydrologic reconstruction, comparative hydrology and model-data learning. These strategies focus on understanding hydrologic processes and feedbacks over long timescales, across many locations, and through strategic coupling of observational and model data in specific systems. We highlight the value of use-inspired and team-based science that is motivated by real-world hydrologic problems but targets improvements in fundamental understanding to support decision-making and management.

An Overview of the NASA Energy and Water cycle Study (NEWS) and the North American Water Program (NAWP)

NASA Astrophysics Data System (ADS)

Houser, P. R.

2014-12-01

NEWS: 10 years ago, NASA established the NASA Energy and Water-cycle Study (NEWS), whose long-term grand challenge is to document and enable improved, observationally based, predictions of water and energy cycle consequences of Earth system variability and change. The NEWS program builds upon existing NASA-supported basic research in atmospheric physics and dynamics, radiation, climate modeling, and terrestrial hydrology. While these NASA programs fund research activities that address individual aspects of the global energy and water cycles, they are not specifically designed to generate a coordinated result. NEWS developed the first coordinated attempt to describe the complete global energy and water cycle using existing and forthcoming satellite and ground based observations, and laying the foundation for essential NEWS developments in model representations of atmospheric energy and water exchange processes. This comprehensive energy and water data analysis program exploited crucial datasets, some requiring complete re-processing, and new satellite measurements. NAWP: Dramatically changing climates has had an indelible impact on North America's water crisis. To decisively address these challenges, we recommend that NAWP coalesce an interdisciplinary, international and interagency effort to make significant contributions to continental- to decision-scale hydroclimate science and solutions. By entraining, integrating and coordinating the vast array of interdisciplinary observational and prediction resources available, NAWP will significantly advance skill in predicting, assessing and managing variability and changes in North American water resources. We adopt three challenges to organize NAWP efforts. The first deals with developing a scientific basis and tools for mitigating and adapting to changes in the water supply-demand balance. The second challenge is benchmarking; to use incomplete and uncertain observations to assess water storage and quality dynamics, and to characterize the information content of water cycle predictions in a way that allows for model improvement. The final challenge is to establish clear pathways to inform water managers, practitioners and decision makers about newly developed tools, observations and research results.

LARP Long Quadrupole: A "Long" Step Toward an LHC

ScienceCinema

Giorgio Ambrosio

2017-12-09

The beginning of the development of Nb3Sn magnets for particle accelerators goes back to the 1960’s. But only very recently has this development begun to face the challenges of fabricating Nb3Sn magnets which can meet the requirements of modern particle accelerators. LARP (the LHC Accelerator Research Program) is leading this effort focusing on long models of the Interaction Region quadrupoles for a possible luminosity upgrade of the Large Hadron Collider. A major milestone in this development is to test, by the end of 2009, 4m-long quadrupole models, which will be the first Nb3Sn accelerator-type magnets approaching the length of real accelerator magnets. The Long Quadrupoles (LQ) are “Proof-of-Principle” magnets which are to demonstrate that Nb3Sn technology is sufficiently mature for use in high energy particle accelerators. Their design is based on the LARP Technological Quadrupole (TQ) models, under development at FNAL and LBNL, which have design gradients higher than 200 T/m and an aperture of 90 mm. Several challenges must be addressed for the successful fabrication of long Nb3Sn coils and magnets. These challenges and the solutions adopted will be presented together with the main features of the LQ magnets. Several R&D lines are participating to this effort and their contributions will be also presented.

Developing Flexible Discrete Event Simulation Models in an Uncertain Policy Environment

NASA Technical Reports Server (NTRS)

Miranda, David J.; Fayez, Sam; Steele, Martin J.

2011-01-01

On February 1st, 2010 U.S. President Barack Obama submitted to Congress his proposed budget request for Fiscal Year 2011. This budget included significant changes to the National Aeronautics and Space Administration (NASA), including the proposed cancellation of the Constellation Program. This change proved to be controversial and Congressional approval of the program's official cancellation would take many months to complete. During this same period an end-to-end discrete event simulation (DES) model of Constellation operations was being built through the joint efforts of Productivity Apex Inc. (PAl) and Science Applications International Corporation (SAIC) teams under the guidance of NASA. The uncertainty in regards to the Constellation program presented a major challenge to the DES team, as to: continue the development of this program-of-record simulation, while at the same time remain prepared for possible changes to the program. This required the team to rethink how it would develop it's model and make it flexible enough to support possible future vehicles while at the same time be specific enough to support the program-of-record. This challenge was compounded by the fact that this model was being developed through the traditional DES process-orientation which lacked the flexibility of object-oriented approaches. The team met this challenge through significant pre-planning that led to the "modularization" of the model's structure by identifying what was generic, finding natural logic break points, and the standardization of interlogic numbering system. The outcome of this work resulted in a model that not only was ready to be easily modified to support any future rocket programs, but also a model that was extremely structured and organized in a way that facilitated rapid verification. This paper discusses in detail the process the team followed to build this model and the many advantages this method provides builders of traditional process-oriented discrete event simulations.

Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models.

PubMed

Rivera-Hernandez, Tania; Pandey, Manisha; Henningham, Anna; Cole, Jason; Choudhury, Biswa; Cork, Amanda J; Gillen, Christine M; Ghaffar, Khairunnisa Abdul; West, Nicholas P; Silvestri, Guido; Good, Michael F; Moyle, Peter M; Toth, Istvan; Nizet, Victor; Batzloff, Michael R; Walker, Mark J

2016-06-14

Group A Streptococcus (GAS) is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i) streptolysin O (SLO), interleukin 8 (IL-8) protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP]), group A streptococcal C5a peptidase (SCPA), arginine deiminase (ADI), and trigger factor (TF); (ii) the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii) group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a "gold standard" for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model. This set of experiments demonstrates the inherent variability of mouse models for the characterization of GAS vaccine candidate protective efficacy. Such variability poses an important challenge for GAS vaccine development, as advancement of candidates to human clinical trials requires strong evidence of efficacy. This study highlights the need for an open discussion within the field regarding standardization of animal models for GAS vaccine development. Copyright © 2016 Rivera-Hernandez et al.

Ensemble method for dengue prediction.

PubMed

Buczak, Anna L; Baugher, Benjamin; Moniz, Linda J; Bagley, Thomas; Babin, Steven M; Guven, Erhan

2018-01-01

In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico) during four dengue seasons: 1) peak height (i.e., maximum weekly number of cases during a transmission season; 2) peak week (i.e., week in which the maximum weekly number of cases occurred); and 3) total number of cases reported during a transmission season. A dengue transmission season is the 12-month period commencing with the location-specific, historical week with the lowest number of cases. At the beginning of the Dengue Challenge, participants were provided with the same input data for developing the models, with the prediction testing data provided at a later date. Our approach used ensemble models created by combining three disparate types of component models: 1) two-dimensional Method of Analogues models incorporating both dengue and climate data; 2) additive seasonal Holt-Winters models with and without wavelet smoothing; and 3) simple historical models. Of the individual component models created, those with the best performance on the prior four years of data were incorporated into the ensemble models. There were separate ensembles for predicting each of the three targets at each of the two locations. Our ensemble models scored higher for peak height and total dengue case counts reported in a transmission season for Iquitos than all other models submitted to the Dengue Challenge. However, the ensemble models did not do nearly as well when predicting the peak week. The Dengue Challenge organizers scored the dengue predictions of the Challenge participant groups. Our ensemble approach was the best in predicting the total number of dengue cases reported for transmission season and peak height for Iquitos, Peru.

Ensemble method for dengue prediction

PubMed Central

Baugher, Benjamin; Moniz, Linda J.; Bagley, Thomas; Babin, Steven M.; Guven, Erhan

2018-01-01

Background In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico) during four dengue seasons: 1) peak height (i.e., maximum weekly number of cases during a transmission season; 2) peak week (i.e., week in which the maximum weekly number of cases occurred); and 3) total number of cases reported during a transmission season. A dengue transmission season is the 12-month period commencing with the location-specific, historical week with the lowest number of cases. At the beginning of the Dengue Challenge, participants were provided with the same input data for developing the models, with the prediction testing data provided at a later date. Methods Our approach used ensemble models created by combining three disparate types of component models: 1) two-dimensional Method of Analogues models incorporating both dengue and climate data; 2) additive seasonal Holt-Winters models with and without wavelet smoothing; and 3) simple historical models. Of the individual component models created, those with the best performance on the prior four years of data were incorporated into the ensemble models. There were separate ensembles for predicting each of the three targets at each of the two locations. Principal findings Our ensemble models scored higher for peak height and total dengue case counts reported in a transmission season for Iquitos than all other models submitted to the Dengue Challenge. However, the ensemble models did not do nearly as well when predicting the peak week. Conclusions The Dengue Challenge organizers scored the dengue predictions of the Challenge participant groups. Our ensemble approach was the best in predicting the total number of dengue cases reported for transmission season and peak height for Iquitos, Peru. PMID:29298320

Computational Molecular Modeling for Evaluating the Toxicity of Environmental Chemicals: Prioritizing Bioassay Requirements

EPA Science Inventory

This commentary provides an overview of the challenges that arise from applying molecular modeling tools developed and commonly used for pharmaceutical discovery to the problem of predicting the potential toxicities of environmental chemicals.

The Mock LISA Data Challenge Round 3: New and Improved Sources

NASA Technical Reports Server (NTRS)

Baker, John

2008-01-01

The Mock LISA Data Challenges are a program to demonstrate and encourage the development of data-analysis capabilities for LISA. Each round of challenges consists of several data sets containing simulated instrument noise and gravitational waves from sources of undisclosed parameters. Participants are asked to analyze the data sets and report the maximum information they can infer about the source parameters. The challenges are being released in rounds of increasing complexity and realism. Challenge 3. currently in progress, brings new source classes, now including cosmic-string cusps and primordial stochastic backgrounds, and more realistic signal models for supermassive black-hole inspirals and galactic double white dwarf binaries.

A multiresolution method for climate system modeling: application of spherical centroidal Voronoi tessellations

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

Ringler, Todd; Ju, Lili; Gunzburger, Max

2008-11-14

During the next decade and beyond, climate system models will be challenged to resolve scales and processes that are far beyond their current scope. Each climate system component has its prototypical example of an unresolved process that may strongly influence the global climate system, ranging from eddy activity within ocean models, to ice streams within ice sheet models, to surface hydrological processes within land system models, to cloud processes within atmosphere models. These new demands will almost certainly result in the develop of multiresolution schemes that are able, at least regionally, to faithfully simulate these fine-scale processes. Spherical centroidal Voronoimore » tessellations (SCVTs) offer one potential path toward the development of a robust, multiresolution climate system model components. SCVTs allow for the generation of high quality Voronoi diagrams and Delaunay triangulations through the use of an intuitive, user-defined density function. In each of the examples provided, this method results in high-quality meshes where the quality measures are guaranteed to improve as the number of nodes is increased. Real-world examples are developed for the Greenland ice sheet and the North Atlantic ocean. Idealized examples are developed for ocean–ice shelf interaction and for regional atmospheric modeling. In addition to defining, developing, and exhibiting SCVTs, we pair this mesh generation technique with a previously developed finite-volume method. Our numerical example is based on the nonlinear, shallow water equations spanning the entire surface of the sphere. This example is used to elucidate both the potential benefits of this multiresolution method and the challenges ahead.« less

Next generation human skin constructs as advanced tools for drug development.

PubMed

Abaci, H E; Guo, Zongyou; Doucet, Yanne; Jacków, Joanna; Christiano, Angela

2017-11-01

Many diseases, as well as side effects of drugs, manifest themselves through skin symptoms. Skin is a complex tissue that hosts various specialized cell types and performs many roles including physical barrier, immune and sensory functions. Therefore, modeling skin in vitro presents technical challenges for tissue engineering. Since the first attempts at engineering human epidermis in 1970s, there has been a growing interest in generating full-thickness skin constructs mimicking physiological functions by incorporating various skin components, such as vasculature and melanocytes for pigmentation. Development of biomimetic in vitro human skin models with these physiological functions provides a new tool for drug discovery, disease modeling, regenerative medicine and basic research for skin biology. This goal, however, has long been delayed by the limited availability of different cell types, the challenges in establishing co-culture conditions, and the ability to recapitulate the 3D anatomy of the skin. Recent breakthroughs in induced pluripotent stem cell (iPSC) technology and microfabrication techniques such as 3D-printing have allowed for building more reliable and complex in vitro skin models for pharmaceutical screening. In this review, we focus on the current developments and prevailing challenges in generating skin constructs with vasculature, skin appendages such as hair follicles, pigmentation, immune response, innervation, and hypodermis. Furthermore, we discuss the promising advances that iPSC technology offers in order to generate in vitro models of genetic skin diseases, such as epidermolysis bullosa and psoriasis. We also discuss how future integration of the next generation human skin constructs onto microfluidic platforms along with other tissues could revolutionize the early stages of drug development by creating reliable evaluation of patient-specific effects of pharmaceutical agents. Impact statement Skin is a complex tissue that hosts various specialized cell types and performs many roles including barrier, immune, and sensory functions. For human-relevant drug testing, there has been a growing interest in building more physiological skin constructs by incorporating different skin components, such as vasculature, appendages, pigment, innervation, and adipose tissue. This paper provides an overview of the strategies to build complex human skin constructs that can faithfully recapitulate human skin and thus can be used in drug development targeting skin diseases. In particular, we discuss recent developments and remaining challenges in incorporating various skin components, availability of iPSC-derived skin cell types and in vitro skin disease models. In addition, we provide insights on the future integration of these complex skin models with other organs on microfluidic platforms as well as potential readout technologies for high-throughput drug screening.

An entrustable professional activity (EPA) for handoffs as a model for EPA assessment development.

PubMed

Aylward, Michael; Nixon, James; Gladding, Sophia

2014-10-01

Medical education is moving toward assessment of educational outcomes rather than educational processes. The American Board of Internal Medicine and American Board of Pediatrics milestones and the concept of entrustable professional activities (EPA)--skills essential to the practice of medicine that educators progressively entrust learners to perform--provide new approaches to assessing outcomes. Although some defined EPAs exist for internal medicine and pediatrics, the continued development and implementation of EPAs remains challenging. As residency programs are expected to begin reporting milestone-based performance, however, they will need examples of how to overcome these challenges. The authors describe a model for the development and implementation of an EPA using the resident handoff as an example. The model includes nine steps: selecting the EPA, determining where skills are practiced and assessed, addressing barriers to assessment, determining components of the EPA, determining needed assessment tools, developing new assessments if needed, determining criteria for advancement through entrustment levels, mapping milestones to the EPA, and faculty development. Following implementation, 78% of interns at the University of Minnesota Medical School were observed giving handoffs and provided feedback. The authors suggest that this model of EPA development--which includes engaging stakeholders, an iterative process to describing the behavioral characteristics of each domain at each level of entrustment, and the development of specific assessment tools that support both formative feedback and summative decisions about entrustment--can serve as a model for EPA development for other clinical skills and specialty areas.

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

Adam, J. C.; Stephens, J. C.; Chung, Serena

As managers of agricultural and natural resources are confronted with uncertainties in global change impacts, the complexities associated with the interconnected cycling of nitrogen, carbon, and water present daunting management challenges. Existing models provide detailed information on specific sub-systems (land, air, water, economics, etc). An increasing awareness of the unintended consequences of management decisions resulting from interconnectedness of these sub-systems, however, necessitates coupled regional earth system models (EaSMs). Decision makers’ needs and priorities can be integrated into the model design and development processes to enhance decision-making relevance and "usability" of EaSMs. BioEarth is a current research initiative with a focusmore » on the U.S. Pacific Northwest region that explores the coupling of multiple stand-alone EaSMs to generate usable information for resource decision-making. Direct engagement between model developers and non-academic stakeholders involved in resource and environmental management decisions throughout the model development process is a critical component of this effort. BioEarth utilizes a "bottom-up" approach, upscaling a catchment-scale model to basin and regional scales, as opposed to the "top-down" approach of downscaling global models utilized by most other EaSM efforts. This paper describes the BioEarth initiative and highlights opportunities and challenges associated with coupling multiple stand-alone models to generate usable information for agricultural and natural resource decision-making.« less

Placing biodiversity in ecosystem models without getting lost in translation

NASA Astrophysics Data System (ADS)

Queirós, Ana M.; Bruggeman, Jorn; Stephens, Nicholas; Artioli, Yuri; Butenschön, Momme; Blackford, Jeremy C.; Widdicombe, Stephen; Allen, J. Icarus; Somerfield, Paul J.

2015-04-01

A key challenge to progressing our understanding of biodiversity's role in the sustenance of ecosystem function is the extrapolation of the results of two decades of dedicated empirical research to regional, global and future landscapes. Ecosystem models provide a platform for this progression, potentially offering a holistic view of ecosystems where, guided by the mechanistic understanding of processes and their connection to the environment and biota, large-scale questions can be investigated. While the benefits of depicting biodiversity in such models are widely recognized, its application is limited by difficulties in the transfer of knowledge from small process oriented ecology into macro-scale modelling. Here, we build on previous work, breaking down key challenges of that knowledge transfer into a tangible framework, highlighting successful strategies that both modelling and ecology communities have developed to better interact with one another. We use a benthic and a pelagic case-study to illustrate how aspects of the links between biodiversity and ecosystem process have been depicted in marine ecosystem models (ERSEM and MIRO), from data, to conceptualisation and model development. We hope that this framework may help future interactions between biodiversity researchers and model developers by highlighting concrete solutions to common problems, and in this way contribute to the advance of the mechanistic understanding of the role of biodiversity in marine (and terrestrial) ecosystems.

Development of anti-inflammatory drugs - the research and development process.

PubMed

Knowles, Richard Graham

2014-01-01

The research and development process for novel drugs to treat inflammatory diseases is described, and several current issues and debates relevant to this are raised: the decline in productivity, attrition, challenges and trends in developing anti-inflammatory drugs, the poor clinical predictivity of experimental models of inflammatory diseases, heterogeneity within inflammatory diseases, 'improving on the Beatles' in treating inflammation, and the relationships between big pharma and biotechs. The pharmaceutical research and development community is responding to these challenges in multiple ways which it is hoped will lead to the discovery and development of a new generation of anti-inflammatory medicines. © 2013 Nordic Pharmacological Society. Published by John Wiley & Sons Ltd.

The Asian Human Resource Approach in Global Perspective.

ERIC Educational Resources Information Center

Cummings, William K.

1995-01-01

Challenges the prevailing Western approach to education by asserting that several Asian nations have and are developing a distinctive approach to human resource development. Describes characteristics of this approach and contrasts it to the Western model. (CFR)

Travel Demand Model Development and Application Guidelines (Rev.)

DOT National Transportation Integrated Search

1995-06-01

There is a new challenge confronting state and regional agencies -- the : selection and development of appropriate analysis tools for application to the : planning problems presented by the 1990 Federal Clear Air Act Amendments (CAAA), : the 1991 Fed...

Future supply chains enabled by continuous processing--opportunities and challenges. May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Srai, Jagjit Singh; Badman, Clive; Krumme, Markus; Futran, Mauricio; Johnston, Craig

2015-03-01

This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily "continuous processing"-based supply chain. The current predominantly "large batch" and centralized manufacturing system designed for the "blockbuster" drug has driven a slow-paced, inventory heavy operating model that is increasingly regarded as inflexible and unsustainable. Indeed, new markets and the rapidly evolving technology landscape will drive more product variety, shorter product life-cycles, and smaller drug volumes, which will exacerbate an already unsustainable economic model. Future supply chains will be required to enhance affordability and availability for patients and healthcare providers alike despite the increased product complexity. In this more challenging supply scenario, we examine the potential for a more pull driven, near real-time demand-based supply chain, utilizing continuous processing where appropriate as a key element of a more "flow-through" operating model. In this discussion paper on future supply chain models underpinned by developments in the continuous manufacture of pharmaceuticals, we have set out; The significant opportunities to moving to a supply chain flow-through operating model, with substantial opportunities in inventory reduction, lead-time to patient, and radically different product assurance/stability regimes. Scenarios for decentralized production models producing a greater variety of products with enhanced volume flexibility. Production, supply, and value chain footprints that are radically different from today's monolithic and centralized batch manufacturing operations. Clinical trial and drug product development cost savings that support more rapid scale-up and market entry models with early involvement of SC designers within New Product Development. The major supply chain and industrial transformational challenges that need to be addressed. The paper recognizes that although current batch operational performance in pharma is far from optimal and not necessarily an appropriate end-state benchmark for batch technology, the adoption of continuous supply chain operating models underpinned by continuous production processing, as full or hybrid solutions in selected product supply chains, can support industry transformations to deliver right-first-time quality at substantially lower inventory profiles. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Animal models of asthma: utility and limitations.

PubMed

Aun, Marcelo Vivolo; Bonamichi-Santos, Rafael; Arantes-Costa, Fernanda Magalhães; Kalil, Jorge; Giavina-Bianchi, Pedro

2017-01-01

Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as Drosophila , rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes of allergen administration.

Partners in Research: Developing a Model for Undergraduate Faculty-Student Collaboration.

PubMed

Reitmaier Koehler, Amy; Reveling Smith, Linda; Davies, Susan; Mangan-Danckwart, Deborah

2015-10-09

Maintaining scholarship while delivering an undergraduate nursing program is a challenge for nursing faculty. In this paper, we describe an approach that involves undergraduate nursing students in a program of faculty research, which evaluates new approaches to teaching and learning. Students work with faculty to develop a research proposal, identifying specific questions and exploring relevant literature. Projects may include original data collection with faculty supervision, or secondary analysis of existing datasets. Foci have included partnership learning between nursing students and older adults, models of sustainability for a traveling health clinic, and experiences of aging. Findings and recommendations feed into the broader faculty research agenda, provide a foundation for subsequent projects, and inform further development of educational programs. Students have presented at local and national conferences and developed papers for publication based on this joint work. We describe the benefits and challenges of these partnerships, drawing upon student and faculty reflections.

Sustainability of cross-functional teams for marketing strategy development and implementation.

PubMed

Kono, Ken; Antonucci, Don

2006-01-01

This article presents a case study on a cross-functional team used for marketing strategy development and execution at a health insurance company. The study found a set of success factors that contributed to the initial success of the team, but the factors were not enough to maintain the team's high level of productivity over time. The study later identified a set of 8 factors that helped sustain the team's high-productivity level. The 2 sets (ie, success and its subsequent sustainability factors) are analyzed against a normative model of team effectiveness. All the factors are explained by the normative model except for 1 sustainability factor, "challenge motivator." In fact, the study found the "challenge motivator" to be the most critical factor to keep up the team's productivity over time. Apart from a performance crisis, the authors developed 3 "challenge motivators"--first, more granular market information that could unearth hidden performance issues; second, constant value creation to shareholders as the firm being publicly traded; and third, the firm's strategic mandate to meet and exceed customer expectations that puts ultimate performance pressure on the marketing strategy team.

Early Career Professional Development Issues for Military Academic Psychiatrists

ERIC Educational Resources Information Center

Warner, Christopher H.; Bobo, William V.; Flynn, Julianne

2005-01-01

Objective: Academically motivated graduates of military psychiatric residency programs confront serious challenges. Method: In this article, the authors present a junior faculty development model organized around four overlapping domains: mentorship, scholarship, research, and career planning/development. Using these four domains as a platform for…

Characterizing land use change in multidisciplinary landscape-level analyses.

Treesearch

Jeffrey D. Kline

2003-01-01

Economists increasingly face opportunities to collaborate with ecologists on landscape-level analyses of socioeconomic and ecological processes. This often calls for developing empirical models to project land use change as input into ecological models. Providing ecologists with the land use information they desire can present many challenges regarding data, modeling,...

Using a Participatory Culture-Specific Model to Increase the Effectiveness of Social Justice Courses in School Psychology

ERIC Educational Resources Information Center

Graybill, Emily C.; Varjas, Kris; Meyers, Joel; Greenberg, Daphne; Roach, Andrew T.

2013-01-01

The Participatory Culture-Specific Model of Course Development (PCSMCD), adapted from the Participatory Culture-Specific Intervention Model, is a proposed framework to address challenges to social justice education by addressing the following four course variables: instructor characteristics, instructor experiences, student characteristics, and…

AP233: An Information Model for Systems Engineering

NASA Technical Reports Server (NTRS)

Siebes, Georg

2009-01-01

In today's world, information is abundant. We have no problems generating it. But we are challenged to find, organize, and exchange information. center dot A standardized model of information can help. Such a model nearly completed its development for Systems Engineering. It is referred to as AP233 (AP = Application Protocol).

An Engineered Organoid Culture Model That Incorporates Human Mesenchymal and Epithelial Cells to Model Palatal Fusion.

EPA Science Inventory

During embryonic development, fusion events are critical to morphogenesis of organs and tissues, including the iris, urethra, heart, neural tube, and secondary palate. Modeling this process in vitro is challenging as the interactions of mesenchymal and epithelial cells can be cr...

Feasibility of Representing a Danish Microbiology Model Using FHIR.

PubMed

Andersen, Mie Vestergaard; Kristensen, Ida Hvass; Larsen, Malene Møller; Pedersen, Claus Hougaard; Gøeg, Kirstine Rosenbeck; Pape-Haugaard, Louise B

2017-01-01

Achieving interoperability in health is a challenge and requires standardization. The newly developed HL7 standard: Fast Healthcare Interoperability Resources (FHIR) promises both flexibility and interoperability. This study investigates the feasibility of expressing a Danish microbiology message model content in FHIR to explore whether complex in-use legacy models can be migrated and what challenges this may pose. The Danish microbiology message model (the DMM) is used as a case to illustrate challenges and opportunities accosted with applying the FHIR standard. Mapping of content from DMM to FHIR was done as close as possible to the DMM to minimize migration costs except when the structure of the content did not fit into FHIR. From the DMM a total of 183 elements were mapped to FHIR. 75 (40.9%) elements were modeled as existing FHIR elements and 96 (52.5%) elements were modeled as extensions and 12 (6.6%) elements were deemed unnecessary because of build-in FHIR characteristics. In this study, it was possible to represent the content of a Danish message model using HL7 FHIR.

A Systems Approach to Scalable Transportation Network Modeling

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

Perumalla, Kalyan S

2006-01-01

Emerging needs in transportation network modeling and simulation are raising new challenges with respect to scal-ability of network size and vehicular traffic intensity, speed of simulation for simulation-based optimization, and fidel-ity of vehicular behavior for accurate capture of event phe-nomena. Parallel execution is warranted to sustain the re-quired detail, size and speed. However, few parallel simulators exist for such applications, partly due to the challenges underlying their development. Moreover, many simulators are based on time-stepped models, which can be computationally inefficient for the purposes of modeling evacuation traffic. Here an approach is presented to de-signing a simulator with memory andmore » speed efficiency as the goals from the outset, and, specifically, scalability via parallel execution. The design makes use of discrete event modeling techniques as well as parallel simulation meth-ods. Our simulator, called SCATTER, is being developed, incorporating such design considerations. Preliminary per-formance results are presented on benchmark road net-works, showing scalability to one million vehicles simu-lated on one processor.« less

Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation.

PubMed

Renukaradhya, Gourapura J; Narasimhan, Balaji; Mallapragada, Surya K

2015-12-10

Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers - 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, is discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections. Copyright © 2015 Elsevier B.V. All rights reserved.

An integrative model of the impairments in insight in schizophrenia: emerging research on causal factors and treatments.

PubMed

Vohs, Jenifer L; George, Sunita; Leonhardt, Bethany L; Lysaker, Paul H

2016-10-01

Poor insight, or unawareness of some major aspect of mental illness, is a major barrier to wellness when it interferes with persons seeking out treatment or forming their own understanding of the challenges they face. One barrier to addressing impaired insight is the absence of a comprehensive model of how poor insight develops. To explore this issue we review how poor insight is the result of multiple phenomena which interfere with the construction of narrative accounts of psychiatric challenges, rather than a single social or biological cause. Expert commentary: We propose an integrative model of poor insight in schizophrenia which involves the interaction of symptoms, deficits in neurocognition, social cognition, metacognition, and stigma. Emerging treatments for poor insight including therapies which focus on the development of metacognition are discussed.

Developing Staffing Models to Support Population Health Management And Quality Oucomes in Ambulatory Care Settings.

PubMed

Haas, Sheila A; Vlasses, Frances; Havey, Julia

2016-01-01

There are multiple demands and challenges inherent in establishing staffing models in ambulatory heath care settings today. If health care administrators establish a supportive physical and interpersonal health care environment, and develop high-performing interprofessional teams and staffing models and electronic documentation systems that track performance, patients will have more opportunities to receive safe, high-quality evidence-based care that encourages patient participation in decision making, as well as provision of their care. The health care organization must be aligned and responsive to the community within which it resides, fully invested in population health management, and continuously scanning the environment for competitive, regulatory, and external environmental risks. All of these challenges require highly competent providers willing to change attitudes and culture such as movement toward collaborative practice among the interprofessional team including the patient.

Open challenges in structure-based virtual screening: Receptor modeling, target flexibility consideration and active site water molecules description.

PubMed

Spyrakis, Francesca; Cavasotto, Claudio N

2015-10-01

Structure-based virtual screening is currently an established tool in drug lead discovery projects. Although in the last years the field saw an impressive progress in terms of algorithm development, computational performance, and retrospective and prospective applications in ligand identification, there are still long-standing challenges where further improvement is needed. In this review, we consider the conceptual frame, state-of-the-art and recent developments of three critical "structural" issues in structure-based drug lead discovery: the use of homology modeling to accurately model the binding site when no experimental structures are available, the necessity of accounting for the dynamics of intrinsically flexible systems as proteins, and the importance of considering active site water molecules in lead identification and optimization campaigns. Copyright © 2015 Elsevier Inc. All rights reserved.

Challenges in Visual Analysis of Ensembles

DOE PAGES

Crossno, Patricia

2018-04-12

Modeling physical phenomena through computational simulation increasingly relies on generating a collection of related runs, known as an ensemble. In this paper, we explore the challenges we face in developing analysis and visualization systems for large and complex ensemble data sets, which we seek to understand without having to view the results of every simulation run. Implementing approaches and ideas developed in response to this goal, we demonstrate the analysis of a 15K run material fracturing study using Slycat, our ensemble analysis system.

Challenges in Visual Analysis of Ensembles

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

Crossno, Patricia

Modeling physical phenomena through computational simulation increasingly relies on generating a collection of related runs, known as an ensemble. In this paper, we explore the challenges we face in developing analysis and visualization systems for large and complex ensemble data sets, which we seek to understand without having to view the results of every simulation run. Implementing approaches and ideas developed in response to this goal, we demonstrate the analysis of a 15K run material fracturing study using Slycat, our ensemble analysis system.

Environmental fate and exposure models: advances and challenges in 21st century chemical risk assessment.

PubMed

Di Guardo, Antonio; Gouin, Todd; MacLeod, Matthew; Scheringer, Martin

2018-01-24

Environmental fate and exposure models are a powerful means to integrate information on chemicals, their partitioning and degradation behaviour, the environmental scenario and the emissions in order to compile a picture of chemical distribution and fluxes in the multimedia environment. A 1995 pioneering book, resulting from a series of workshops among model developers and users, reported the main advantages and identified needs for research in the field of multimedia fate models. Considerable efforts were devoted to their improvement in the past 25 years and many aspects were refined; notably the inclusion of nanomaterials among the modelled substances, the development of models at different spatial and temporal scales, the estimation of chemical properties and emission data, the incorporation of additional environmental media and processes, the integration of sensitivity and uncertainty analysis in the simulations. However, some challenging issues remain and require research efforts and attention: the need of methods to estimate partition coefficients for polar and ionizable chemical in the environment, a better description of bioavailability in different environments as well as the requirement of injecting more ecological realism in exposure predictions to account for the diversity of ecosystem structures and functions in risk assessment. Finally, to transfer new scientific developments into the realm of regulatory risk assessment, we propose the formation of expert groups that compare, discuss and recommend model modifications and updates and help develop practical tools for risk assessment.

Using natural selection and optimization for smarter vegetation models - challenges and opportunities

NASA Astrophysics Data System (ADS)

Franklin, Oskar; Han, Wang; Dieckmann, Ulf; Cramer, Wolfgang; Brännström, Åke; Pietsch, Stephan; Rovenskaya, Elena; Prentice, Iain Colin

2017-04-01

Dynamic global vegetation models (DGVMs) are now indispensable for understanding the biosphere and for estimating the capacity of ecosystems to provide services. The models are continuously developed to include an increasing number of processes and to utilize the growing amounts of observed data becoming available. However, while the versatility of the models is increasing as new processes and variables are added, their accuracy suffers from the accumulation of uncertainty, especially in the absence of overarching principles controlling their concerted behaviour. We have initiated a collaborative working group to address this problem based on a 'missing law' - adaptation and optimization principles rooted in natural selection. Even though this 'missing law' constrains relationships between traits, and therefore can vastly reduce the number of uncertain parameters in ecosystem models, it has rarely been applied to DGVMs. Our recent research have shown that optimization- and trait-based models of gross primary production can be both much simpler and more accurate than current models based on fixed functional types, and that observed plant carbon allocations and distributions of plant functional traits are predictable with eco-evolutionary models. While there are also many other examples of the usefulness of these and other theoretical principles, it is not always straight-forward to make them operational in predictive models. In particular on longer time scales, the representation of functional diversity and the dynamical interactions among individuals and species presents a formidable challenge. Here we will present recent ideas on the use of adaptation and optimization principles in vegetation models, including examples of promising developments, but also limitations of the principles and some key challenges.

An Agent Based Collaborative Simplification of 3D Mesh Model

NASA Astrophysics Data System (ADS)

Wang, Li-Rong; Yu, Bo; Hagiwara, Ichiro

Large-volume mesh model faces the challenge in fast rendering and transmission by Internet. The current mesh models obtained by using three-dimensional (3D) scanning technology are usually very large in data volume. This paper develops a mobile agent based collaborative environment on the development platform of mobile-C. Communication among distributed agents includes grasping image of visualized mesh model, annotation to grasped image and instant message. Remote and collaborative simplification can be efficiently conducted by Internet.

Calibration and validation of coarse-grained models of atomic systems: application to semiconductor manufacturing

NASA Astrophysics Data System (ADS)

Farrell, Kathryn; Oden, J. Tinsley

2014-07-01

Coarse-grained models of atomic systems, created by aggregating groups of atoms into molecules to reduce the number of degrees of freedom, have been used for decades in important scientific and technological applications. In recent years, interest in developing a more rigorous theory for coarse graining and in assessing the predictivity of coarse-grained models has arisen. In this work, Bayesian methods for the calibration and validation of coarse-grained models of atomistic systems in thermodynamic equilibrium are developed. For specificity, only configurational models of systems in canonical ensembles are considered. Among major challenges in validating coarse-grained models are (1) the development of validation processes that lead to information essential in establishing confidence in the model's ability predict key quantities of interest and (2), above all, the determination of the coarse-grained model itself; that is, the characterization of the molecular architecture, the choice of interaction potentials and thus parameters, which best fit available data. The all-atom model is treated as the "ground truth," and it provides the basis with respect to which properties of the coarse-grained model are compared. This base all-atom model is characterized by an appropriate statistical mechanics framework in this work by canonical ensembles involving only configurational energies. The all-atom model thus supplies data for Bayesian calibration and validation methods for the molecular model. To address the first challenge, we develop priors based on the maximum entropy principle and likelihood functions based on Gaussian approximations of the uncertainties in the parameter-to-observation error. To address challenge (2), we introduce the notion of model plausibilities as a means for model selection. This methodology provides a powerful approach toward constructing coarse-grained models which are most plausible for given all-atom data. We demonstrate the theory and methods through applications to representative atomic structures and we discuss extensions to the validation process for molecular models of polymer structures encountered in certain semiconductor nanomanufacturing processes. The powerful method of model plausibility as a means for selecting interaction potentials for coarse-grained models is discussed in connection with a coarse-grained hexane molecule. Discussions of how all-atom information is used to construct priors are contained in an appendix.

Challenging Situations when Teaching Children with Autism Spectrum Disorders in General Physical Education

ERIC Educational Resources Information Center

Obrusnikova, Iva; Dillon, Suzanna R.

2011-01-01

As the first step of an instrument development, teaching challenges that occur when students with autism spectrum disorders are educated in general physical education were elicited using Goldfried and D'Zurilla's (1969) behavioral-analytic model. Data were collected from a convenience sample of 43 certified physical educators (29 women and 14 men)…

Measuring Fidelity of Implementation--Methodological and Conceptual Issues and Challenges. CRESST Report 811

ERIC Educational Resources Information Center

Osmundson, Ellen; Herman, Joan; Ringstaff, Cathy; Dai, Yunyun; Timms, Mike

2012-01-01

A central challenge in efficacy studies centers on the issue of "fidelity of implementation," that is, the extent to which participants use the curriculum specified by curriculum developers. In this study, we describe and discuss a "fidelity of implementation" model using multiple methods and instruments to compare two versions of a science…

Bebras--A Sustainable Community Building Model for the Concept Based Learning of Informatics and Computational Thinking

ERIC Educational Resources Information Center

Dagiene, Valentina; Stupuriene, Gabriele

2016-01-01

As an international informatics contest, or challenge, Bebras has started the second decade of its existence. The contest attracts more and more countries every year, recently there have been over 40 participating countries. From a single contest-focused annual event Bebras developed to a multifunctional challenge and an activities-based…

Challenges in a Physics Course: Introducing Student-Centred Activities for Increased Learning

ERIC Educational Resources Information Center

Hernandez, Carola; Ravn, Ole; Forero-Shelton, Manu

2014-01-01

This article identifies and analyses some of the challenges that arose in a development process of changing from a content-based teaching environment to a student-centred environment in an undergraduate physics course for medicine and biology students at Universidad de los Andes. Through the use of the Critical Research model proposed by Skovsmose…

Developing School Heads as Instructional Leaders in School-Based Assessment: Challenges and Next Steps

ERIC Educational Resources Information Center

Lingam, Govinda Ishwar; Lingam, Narsamma

2016-01-01

The study explored challenges faced by school leaders in the Pacific nation of Solomon Islands in school-based assessment, and the adequacy of an assessment course to prepare them. A questionnaire including both open and closed-ended questions elicited relevant data from the school leaders. Modelling best practices in school-based assessment was…

Motivation, Challenges, Support (MCS) Cycle Model for the Development of PBL Tutors

ERIC Educational Resources Information Center

Constantinou, Costas S.; Nicolaou, Stella A.

2018-01-01

Problem-Based Learning (PBL) is well known for enhancing students' problem solving skills and teamwork, while the role of PBL tutors is to facilitate discussion rather than teach. This study used four focus groups to explore PBL tutors' motivation, challenges and support mechanisms, and the relationship between these. The study found that there…

Preparing the Principal to Drive the Goals of Education for All: A Conceptual Case Developmental Model

ERIC Educational Resources Information Center

Hutton, Disraeli M.

2014-01-01

The Education for All (EFA) goals, established for countries to improve educational performance, are most challenging for many developing countries. Notwithstanding the challenges, each country must implement suitable programme intervention in order to accomplish these goals. Goal 6 calls for the overall improvement of the education product, which…

Protecting rural communities from terrorism: a statewide, community-based model.

PubMed

Clawson, Art; Brooks, Robert G

2003-01-01

Given the number of Americans who live in rural areas and the unique challenges they face in the provision of health care services, special attention to planning for and responding to terrorist acts is warranted. After September 11, 2001, Florida developed a statewide, community-based model that applies the public health principles of assessment, policy development, and assurance. This model can serve as a possible framework for other states and communities.

Clinical Predictive Modeling Development and Deployment through FHIR Web Services.

PubMed

Khalilia, Mohammed; Choi, Myung; Henderson, Amelia; Iyengar, Sneha; Braunstein, Mark; Sun, Jimeng

2015-01-01

Clinical predictive modeling involves two challenging tasks: model development and model deployment. In this paper we demonstrate a software architecture for developing and deploying clinical predictive models using web services via the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) standard. The services enable model development using electronic health records (EHRs) stored in OMOP CDM databases and model deployment for scoring individual patients through FHIR resources. The MIMIC2 ICU dataset and a synthetic outpatient dataset were transformed into OMOP CDM databases for predictive model development. The resulting predictive models are deployed as FHIR resources, which receive requests of patient information, perform prediction against the deployed predictive model and respond with prediction scores. To assess the practicality of this approach we evaluated the response and prediction time of the FHIR modeling web services. We found the system to be reasonably fast with one second total response time per patient prediction.

Clinical Predictive Modeling Development and Deployment through FHIR Web Services

PubMed Central

Khalilia, Mohammed; Choi, Myung; Henderson, Amelia; Iyengar, Sneha; Braunstein, Mark; Sun, Jimeng

2015-01-01

Clinical predictive modeling involves two challenging tasks: model development and model deployment. In this paper we demonstrate a software architecture for developing and deploying clinical predictive models using web services via the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) standard. The services enable model development using electronic health records (EHRs) stored in OMOP CDM databases and model deployment for scoring individual patients through FHIR resources. The MIMIC2 ICU dataset and a synthetic outpatient dataset were transformed into OMOP CDM databases for predictive model development. The resulting predictive models are deployed as FHIR resources, which receive requests of patient information, perform prediction against the deployed predictive model and respond with prediction scores. To assess the practicality of this approach we evaluated the response and prediction time of the FHIR modeling web services. We found the system to be reasonably fast with one second total response time per patient prediction. PMID:26958207

Development of NASA's Sample Cartridge Assembly: Summary of GEDS Design, Development Testing, and Thermal Analyses

NASA Technical Reports Server (NTRS)

O'Connor, Brian; Hernandez, Deborah; Hornsby, Linda; Brown, Maria; Horton-Mullins, Kathryn

2017-01-01

Outline: Background of ISS (International Space Station) Material Science Research Rack; NASA SCA (Sample Cartridge Assembly) Design; GEDS (Gravitational Effects in Distortion in Sintering) Experiment Ampoule Design; Development Testing Summary; Thermal Modeling and Analysis. Summary: GEDS design development challenging (GEDS Ampoule design developed through MUGS (Microgravity) testing; Short duration transient sample processing; Unable to measure sample temperatures); MUGS Development testing used to gather data (Actual LGF (Low Gradient Furnace)-like furnace response; Provided sample for sintering evaluation); Transient thermal model integral to successful GEDS experiment (Development testing provided furnace response; PI (Performance Indicator) evaluation of sintering anchored model evaluation of processing durations; Thermal transient model used to determine flight SCA sample processing profiles).

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

Dinh, Nam; Athe, Paridhi; Jones, Christopher

The Virtual Environment for Reactor Applications (VERA) code suite is assessed in terms of capability and credibility against the Consortium for Advanced Simulation of Light Water Reactors (CASL) Verification and Validation Plan (presented herein) in the context of three selected challenge problems: CRUD-Induced Power Shift (CIPS), Departure from Nucleate Boiling (DNB), and Pellet-Clad Interaction (PCI). Capability refers to evidence of required functionality for capturing phenomena of interest while capability refers to the evidence that provides confidence in the calculated results. For this assessment, each challenge problem defines a set of phenomenological requirements against which the VERA software is assessed. Thismore » approach, in turn, enables the focused assessment of only those capabilities relevant to the challenge problem. The evaluation of VERA against the challenge problem requirements represents a capability assessment. The mechanism for assessment is the Sandia-developed Predictive Capability Maturity Model (PCMM) that, for this assessment, evaluates VERA on 8 major criteria: (1) Representation and Geometric Fidelity, (2) Physics and Material Model Fidelity, (3) Software Quality Assurance and Engineering, (4) Code Verification, (5) Solution Verification, (6) Separate Effects Model Validation, (7) Integral Effects Model Validation, and (8) Uncertainty Quantification. For each attribute, a maturity score from zero to three is assigned in the context of each challenge problem. The evaluation of these eight elements constitutes the credibility assessment for VERA.« less

A Latent Variable Analysis of Continuing Professional Development Constructs Using PLS-SEM Modeling

ERIC Educational Resources Information Center

Yazdi, Mona Tabatabaee; Motallebzadeh, Khalil; Ashraf, Hamid; Baghaei, Purya

2017-01-01

Continuing Professional Development (CPD), in the area of teacher education, refers to the procedures, programs or strategies that help teachers encounter the challenges of their work and accomplish their own and their learning center's goals. To this aim, the purpose of this study is to propose and validate an appropriate model of EFL teachers'…

Development of a Cross-Disciplinary Investigative Model for the Introduction of Microarray Techniques at Non-R1 Undergraduate Institutions

ERIC Educational Resources Information Center

Walker, David E.; Lutz, Gary P.; Alvarez, Consuelo J.

2008-01-01

Integrating advanced biological techniques into instruction at non-R1 institutions can prove to be a challenge. Here, we report the creation of a model for the introduction of gene expression microarray technology into a research laboratory. A student assessment tool was used to evaluate: (1) technical skill development; (2) cross-disciplinary…

Teachers' Professional Development through University-School Partnerships: Theoretical Standpoints and Evidence from Two Pilot Studies in Chile

ERIC Educational Resources Information Center

Grau, Valeska; Calcagni, Elisa; Preiss, David D.; Ortiz, Dominga

2017-01-01

This paper presents a teacher professional development programme, based on a university-schools partnership and a collective reflection model, addressing the needs of in-service teacher education in Chile. First, the main challenges faced by both teachers and teacher education in Chile are summarised. Then, the foundations of this model are…

Seasonal forecasting and health impact models: challenges and opportunities.

PubMed

Ballester, Joan; Lowe, Rachel; Diggle, Peter J; Rodó, Xavier

2016-10-01

After several decades of intensive research, steady improvements in understanding and modeling the climate system have led to the development of the first generation of operational health early warning systems in the era of climate services. These schemes are based on collaborations across scientific disciplines, bringing together real-time climate and health data collection, state-of-the-art seasonal climate predictions, epidemiological impact models based on historical data, and an understanding of end user and stakeholder needs. In this review, we discuss the challenges and opportunities of this complex, multidisciplinary collaboration, with a focus on the factors limiting seasonal forecasting as a source of predictability for climate impact models. © 2016 New York Academy of Sciences.

Application of the NUREG/CR-6850 EPRI/NRC Fire PRA Methodology to a DOE Facility

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

Tom Elicson; Bentley Harwood; Richard Yorg

2011-03-01

The application NUREG/CR-6850 EPRI/NRC fire PRA methodology to DOE facility presented several challenges. This paper documents the process and discusses several insights gained during development of the fire PRA. A brief review of the tasks performed is provided with particular focus on the following: • Tasks 5 and 14: Fire-induced risk model and fire risk quantification. A key lesson learned was to begin model development and quantification as early as possible in the project using screening values and simplified modeling if necessary. • Tasks 3 and 9: Fire PRA cable selection and detailed circuit failure analysis. In retrospect, it wouldmore » have been beneficial to perform the model development and quantification in 2 phases with detailed circuit analysis applied during phase 2. This would have allowed for development of a robust model and quantification earlier in the project and would have provided insights into where to focus the detailed circuit analysis efforts. • Tasks 8 and 11: Scoping fire modeling and detailed fire modeling. More focus should be placed on detailed fire modeling and less focus on scoping fire modeling. This was the approach taken for the fire PRA. • Task 14: Fire risk quantification. Typically, multiple safe shutdown (SSD) components fail during a given fire scenario. Therefore dependent failure analysis is critical to obtaining a meaningful fire risk quantification. Dependent failure analysis for the fire PRA presented several challenges which will be discussed in the full paper.« less

A Crowdsourcing Approach to Developing and Assessing Prediction Algorithms for AML Prognosis

PubMed Central

Noren, David P.; Long, Byron L.; Norel, Raquel; Rrhissorrakrai, Kahn; Hess, Kenneth; Hu, Chenyue Wendy; Bisberg, Alex J.; Schultz, Andre; Engquist, Erik; Liu, Li; Lin, Xihui; Chen, Gregory M.; Xie, Honglei; Hunter, Geoffrey A. M.; Norman, Thea; Friend, Stephen H.; Stolovitzky, Gustavo; Kornblau, Steven; Qutub, Amina A.

2016-01-01

Acute Myeloid Leukemia (AML) is a fatal hematological cancer. The genetic abnormalities underlying AML are extremely heterogeneous among patients, making prognosis and treatment selection very difficult. While clinical proteomics data has the potential to improve prognosis accuracy, thus far, the quantitative means to do so have yet to be developed. Here we report the results and insights gained from the DREAM 9 Acute Myeloid Prediction Outcome Prediction Challenge (AML-OPC), a crowdsourcing effort designed to promote the development of quantitative methods for AML prognosis prediction. We identify the most accurate and robust models in predicting patient response to therapy, remission duration, and overall survival. We further investigate patient response to therapy, a clinically actionable prediction, and find that patients that are classified as resistant to therapy are harder to predict than responsive patients across the 31 models submitted to the challenge. The top two performing models, which held a high sensitivity to these patients, substantially utilized the proteomics data to make predictions. Using these models, we also identify which signaling proteins were useful in predicting patient therapeutic response. PMID:27351836

Hierarchical Bayesian spatial models for multispecies conservation planning and monitoring

Treesearch

Carlos Carroll; Devin S. Johnson; Jeffrey R. Dunk; William J. Zielinski

2010-01-01

Biologists who develop and apply habitat models are often familiar with the statistical challenges posed by their data’s spatial structure but are unsure of whether the use of complex spatial models will increase the utility of model results in planning. We compared the relative performance of nonspatial and hierarchical Bayesian spatial models for three vertebrate and...

Hyperresolution Global Land Surface Modeling: Meeting a Grand Challenge for Monitoring Earth's Terrestrial Water

NASA Technical Reports Server (NTRS)

Wood, Eric F.; Roundy, Joshua K.; Troy, Tara J.; van Beek, L. P. H.; Bierkens, Marc F. P.; 4 Blyth, Eleanor; de Roo, Ad; Doell. Petra; Ek, Mike; Famiglietti, James;

Hyperresolution global land surface modeling: Meeting a grand challenge for monitoring Earth's terrestrial water

NASA Astrophysics Data System (ADS)

Wood, Eric F.; Roundy, Joshua K.; Troy, Tara J.; van Beek, L. P. H.; Bierkens, Marc F. P.; Blyth, Eleanor; de Roo, Ad; DöLl, Petra; Ek, Mike; Famiglietti, James; Gochis, David; van de Giesen, Nick; Houser, Paul; Jaffé, Peter R.; Kollet, Stefan; Lehner, Bernhard; Lettenmaier, Dennis P.; Peters-Lidard, Christa; Sivapalan, Murugesu; Sheffield, Justin; Wade, Andrew; Whitehead, Paul

2011-05-01

Monitoring Earth's terrestrial water conditions is critically important to many hydrological applications such as global food production; assessing water resources sustainability; and flood, drought, and climate change prediction. These needs have motivated the development of pilot monitoring and prediction systems for terrestrial hydrologic and vegetative states, but to date only at the rather coarse spatial resolutions (˜10-100 km) over continental to global domains. Adequately addressing critical water cycle science questions and applications requires systems that are implemented globally at much higher resolutions, on the order of 1 km, resolutions referred to as hyperresolution in the context of global land surface models. This opinion paper sets forth the needs and benefits for a system that would monitor and predict the Earth's terrestrial water, energy, and biogeochemical cycles. We discuss six major challenges in developing a system: improved representation of surface-subsurface interactions due to fine-scale topography and vegetation; improved representation of land-atmospheric interactions and resulting spatial information on soil moisture and evapotranspiration; inclusion of water quality as part of the biogeochemical cycle; representation of human impacts from water management; utilizing massively parallel computer systems and recent computational advances in solving hyperresolution models that will have up to 109 unknowns; and developing the required in situ and remote sensing global data sets. We deem the development of a global hyperresolution model for monitoring the terrestrial water, energy, and biogeochemical cycles a "grand challenge" to the community, and we call upon the international hydrologic community and the hydrological science support infrastructure to endorse the effort.

Expanding the nursing profession.

PubMed

Warr, J; Gobbi, M; Johnson, S

this paper explores the political, economic and demographic developments which are shaping new nursing practices throughout the world. The authors observe that these developments are generally seen to challenge traditional models of nursing and encourage the role of sub-professional support workers.

PBPK models for the prediction of in vivo performance of oral dosage forms.

PubMed

Kostewicz, Edmund S; Aarons, Leon; Bergstrand, Martin; Bolger, Michael B; Galetin, Aleksandra; Hatley, Oliver; Jamei, Masoud; Lloyd, Richard; Pepin, Xavier; Rostami-Hodjegan, Amin; Sjögren, Erik; Tannergren, Christer; Turner, David B; Wagner, Christian; Weitschies, Werner; Dressman, Jennifer

2014-06-16

Drug absorption from the gastrointestinal (GI) tract is a highly complex process dependent upon numerous factors including the physicochemical properties of the drug, characteristics of the formulation and interplay with the underlying physiological properties of the GI tract. The ability to accurately predict oral drug absorption during drug product development is becoming more relevant given the current challenges facing the pharmaceutical industry. Physiologically-based pharmacokinetic (PBPK) modeling provides an approach that enables the plasma concentration-time profiles to be predicted from preclinical in vitro and in vivo data and can thus provide a valuable resource to support decisions at various stages of the drug development process. Whilst there have been quite a few successes with PBPK models identifying key issues in the development of new drugs in vivo, there are still many aspects that need to be addressed in order to maximize the utility of the PBPK models to predict drug absorption, including improving our understanding of conditions in the lower small intestine and colon, taking the influence of disease on GI physiology into account and further exploring the reasons behind population variability. Importantly, there is also a need to create more appropriate in vitro models for testing dosage form performance and to streamline data input from these into the PBPK models. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the current status of PBPK models available. The current challenges in PBPK set-ups for oral drug absorption including the composition of GI luminal contents, transit and hydrodynamics, permeability and intestinal wall metabolism are discussed in detail. Further, the challenges regarding the appropriate integration of results from in vitro models, such as consideration of appropriate integration/estimation of solubility and the complexity of the in vitro release and precipitation data, are also highlighted as important steps to advancing the application of PBPK models in drug development. It is expected that the "innovative" integration of in vitro data from more appropriate in vitro models and the enhancement of the GI physiology component of PBPK models, arising from the OrBiTo project, will lead to a significant enhancement in the ability of PBPK models to successfully predict oral drug absorption and advance their role in preclinical and clinical development, as well as for regulatory applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Modelling challenges for battery materials and electrical energy storage

NASA Astrophysics Data System (ADS)

Muller, Richard P.; Schultz, Peter A.

2013-10-01

Many vital requirements in world-wide energy production, from the electrification of transportation to better utilization of renewable energy production, depend on developing economical, reliable batteries with improved performance characteristics. Batteries reduce the need for gasoline and liquid hydrocarbons in an electrified transportation fleet, but need to be lighter, longer-lived and have higher energy densities, without sacrificing safety. Lighter and higher-capacity batteries make portable electronics more convenient. Less expensive electrical storage accelerates the introduction of renewable energy to electrical grids by buffering intermittent generation from solar or wind. Meeting these needs will probably require dramatic changes in the materials and chemistry used by batteries for electrical energy storage. New simulation capabilities, in both methods and computational resources, promise to fundamentally accelerate and advance the development of improved materials for electric energy storage. To fulfil this promise significant challenges remain, both in accurate simulations at various relevant length scales and in the integration of relevant information across multiple length scales. This focus section of Modelling and Simulation in Materials Science and Engineering surveys the challenges of modelling for energy storage, describes recent successes, identifies remaining challenges, considers various approaches to surmount these challenges and discusses the potential of these methods for future battery development. Zhang et al begin with atoms and electrons, with a review of first-principles studies of the lithiation of silicon electrodes, and then Fan et al examine the development and use of interatomic potentials to the study the mechanical properties of lithiated silicon in larger atomistic simulations. Marrocchelli et al study ionic conduction, an important aspect of lithium-ion battery performance, simulated by molecular dynamics. Emerging high-throughput methods allow rapid screening of promising new candidates for battery materials, illustrated for Li-ion olivine phosphates by Hajiyani et al . This collection includes descriptions of new techniques to model the chemistry at an electrode-electrolyte interface; Gunceler et al demonstrate coupling an electronic description of the electrode chemistry with the fluid electrolyte in a joint density functional theory method. Bridging to longer length scales to probe mechanical properties and transport, Preiss et al present a proof-of-concept phase field approach for a permeation model at an electrochemical interface, An and Jiang examine finite element simulations for transient deformation and transport in electrodes, and Haftabaradaran et al study the application of an analytical model to investigate the critical thickness for fracture in thick film electrodes. The focus section concludes with a study by Chung et al which combines modelling and experiment, examining the validity of the Bruggeman relation for porous electrodes. All of the papers were peer-reviewed following the standard procedure established by the Editorial Board of Modelling and Simulation in Materials Science and Engineering .

Building a sustainable Academic Health Department: the South Carolina model.

PubMed

Smith, Lillian Upton; Waddell, Lisa; Kyle, Joseph; Hand, Gregory A

2014-01-01

Given the limited resources available to public health, it is critical that university programs complement the development needs of agencies. Unfortunately, academic and practice public health entities have long been challenged in building sustainable collaborations that support practice-based research, teaching, and service. The academic health department concept offers a promising solution. In South Carolina, the partners started their academic health department program with a small grant that expanded into a dynamic infrastructure that supports innovative professional exchange and development programs. This article provides a background and describes the key elements of the South Carolina model: joint leadership, a multicomponent memorandum of agreement, and a shared professional development mission. The combination of these elements allows the partners to leverage resources and deftly respond to challenges and opportunities, ultimately fostering the sustainability of the collaboration.

The challenge and promise of anti-epileptic therapy development in animal models

PubMed Central

Simonato, Michele; Brooks-Kayal, Amy R; Engel, Jerome; Galanopoulou, Aristea S; Jensen, Frances E; Moshé, Solomon L; O’Brien, Terence J; Pitkanen, Asla; Wilcox, Karen S; French, Jacqueline A

2016-01-01

Translation of successful target and compound validation studies into clinically effective therapies is a major challenge, with potential for costly clinical trial failures. This situation holds true for the epilepsies—complex diseases with different causes and symptoms. Although the availability of predictive animal models has led to the development of effective antiseizure therapies that are routinely used in clinical practice, showing that translation can be successful, several important unmet therapeutic needs still exist. Available treatments do not fully control seizures in a third of patients with epilepsy, and produce substantial side-effects. No treatment can prevent the development of epilepsy in at-risk patients or cure patients with epilepsy. And no specific treatment for epilepsy-associated comorbidities exists. To meet these demands, a redesign of translational approaches is urgently needed. PMID:25127174

Boxes of Model Building and Visualization.

PubMed

Turk, Dušan

2017-01-01

Macromolecular crystallography and electron microscopy (single-particle and in situ tomography) are merging into a single approach used by the two coalescing scientific communities. The merger is a consequence of technical developments that enabled determination of atomic structures of macromolecules by electron microscopy. Technological progress in experimental methods of macromolecular structure determination, computer hardware, and software changed and continues to change the nature of model building and visualization of molecular structures. However, the increase in automation and availability of structure validation are reducing interactive manual model building to fiddling with details. On the other hand, interactive modeling tools increasingly rely on search and complex energy calculation procedures, which make manually driven changes in geometry increasingly powerful and at the same time less demanding. Thus, the need for accurate manual positioning of a model is decreasing. The user's push only needs to be sufficient to bring the model within the increasing convergence radius of the computing tools. It seems that we can now better than ever determine an average single structure. The tools work better, requirements for engagement of human brain are lowered, and the frontier of intellectual and scientific challenges has moved on. The quest for resolution of new challenges requires out-of-the-box thinking. A few issues such as model bias and correctness of structure, ongoing developments in parameters defining geometric restraints, limitations of the ideal average single structure, and limitations of Bragg spot data are discussed here, together with the challenges that lie ahead.

Supersonics Project - Airport Noise Tech Challenge

NASA Technical Reports Server (NTRS)

Bridges, James

2010-01-01

The Airport Noise Tech Challenge research effort under the Supersonics Project is reviewed. While the goal of "Improved supersonic jet noise models validated on innovative nozzle concepts" remains the same, the success of the research effort has caused the thrust of the research to be modified going forward in time. The main activities from FY06-10 focused on development and validation of jet noise prediction codes. This required innovative diagnostic techniques to be developed and deployed, extensive jet noise and flow databases to be created, and computational tools to be developed and validated. Furthermore, in FY09-10 systems studies commissioned by the Supersonics Project showed that viable supersonic aircraft were within reach using variable cycle engine architectures if exhaust nozzle technology could provide 3-5dB of suppression. The Project then began to focus on integrating the technologies being developed in its Tech Challenge areas to bring about successful system designs. Consequently, the Airport Noise Tech Challenge area has shifted efforts from developing jet noise prediction codes to using them to develop low-noise nozzle concepts for integration into supersonic aircraft. The new plan of research is briefly presented by technology and timelines.

Zika virus vaccines.

PubMed

Abbink, Peter; Stephenson, Kathryn E; Barouch, Dan H

2018-06-19

The recent epidemic of Zika virus (ZIKV) in the Americas has revealed the devastating consequences of ZIKV infection, particularly in pregnant women. Congenital Zika syndrome, characterized by malformations and microcephaly in neonates as well as developmental challenges in children, highlights the need for the development of a safe and effective vaccine. Multiple vaccine candidates have been developed and have shown promising results in both animal models and phase I clinical trials. However, important challenges remain for the clinical development of these vaccines. In this Progress article, we discuss recent preclinical studies and lessons learned from first-in-human clinical trials with ZIKV vaccines.

Full Dome Development for Interactive Immersive Training Capabilities

DTIC Science & Technology

2015-04-03

called the the vDome Player. This application serves as a familiar user interface for direct media playback. Modeled after the widely used VLC ...charrette challenge to task. Below are my notes on where everyone is in planning thei r f inal proj ects . Please let me know (comments or emai l...space with a lot of sound and feeling. What is challenging ? The challenge is how to get depth of field in the dome. Trying to gently allure people into

Comprehensive, multi-modal characterization of an imiquimod-induced human skin inflammation model for drug development.

PubMed

van der Kolk, Tessa; Assil, Salma; Rijneveld, Rianne; Klaassen, Erica S; Feiss, Gary; Florencia, Edwin; Prens, Errol P; Burggraaf, Jacobus; Moerland, Matthijs; Rissmann, Robert; van Doorn, Martijn B A

2018-05-16

Imiquimod (IMQ) is often used as topical challenge agent to provoke local skin inflammation. The objective of this study was to develop and refine a rapid, temporary and reversible human skin inflammation model with IMQ for application in clinical drug development. A randomized, vehicle-controlled, open-label, dose-ranging study was conducted in 16 healthy male subjects. IMQ (5 mg) was applied once daily for 72h under occlusion to intact skin (n = 8) or tape stripped (TS) skin (n = 8). Although IMQ alone induced limited effects, TS+IMQ treatment showed larger responses in several domains including erythema and perfusion (p<0.0001), mRNA expression of inflammatory markers (p<0.01) and inflammatory cell influx compared to vehicle. In conclusion, a rapid, human IMQ skin inflammation challenge model was successfully developed with a clear benefit of TS prior to IMQ application. Future interaction studies will enable proof-of-pharmacology of novel compounds targeting the innate immune system. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Issues and Problems in the Current Development of Vocational Education in China

ERIC Educational Resources Information Center

Shi, Weiping

2013-01-01

Chinese vocational education is currently in its most optimal development period in history. This article discusses several challenges of different dimensions faced by vocational education in China as it develops, such as scale versus quality, development goals, a lifelong vocational education system, and creating model institutions; and puts…

A Software Development Simulation Model of a Spiral Process

NASA Technical Reports Server (NTRS)

Mizell, Carolyn; Malone, Linda

2007-01-01

There is a need for simulation models of software development processes other than the waterfall because processes such as spiral development are becoming more and more popular. The use of a spiral process can make the inherently difficult job of cost and schedule estimation even more challenging due to its evolutionary nature, but this allows for a more flexible process that can better meet customers' needs. This paper will present a discrete event simulation model of spiral development that can be used to analyze cost and schedule effects of using such a process in comparison to a waterfall process.

Software Tools for Developing and Simulating the NASA LaRC CMF Motion Base

NASA Technical Reports Server (NTRS)

Bryant, Richard B., Jr.; Carrelli, David J.

2006-01-01

The NASA Langley Research Center (LaRC) Cockpit Motion Facility (CMF) motion base has provided many design and analysis challenges. In the process of addressing these challenges, a comprehensive suite of software tools was developed. The software tools development began with a detailed MATLAB/Simulink model of the motion base which was used primarily for safety loads prediction, design of the closed loop compensator and development of the motion base safety systems1. A Simulink model of the digital control law, from which a portion of the embedded code is directly generated, was later added to this model to form a closed loop system model. Concurrently, software that runs on a PC was created to display and record motion base parameters. It includes a user interface for controlling time history displays, strip chart displays, data storage, and initializing of function generators used during motion base testing. Finally, a software tool was developed for kinematic analysis and prediction of mechanical clearances for the motion system. These tools work together in an integrated package to support normal operations of the motion base, simulate the end to end operation of the motion base system providing facilities for software-in-the-loop testing, mechanical geometry and sensor data visualizations, and function generator setup and evaluation.

Issues and challenges of involving users in medical device development.

PubMed

Bridgelal Ram, Mala; Grocott, Patricia R; Weir, Heather C M

2008-03-01

User engagement has become a central tenet of health-care policy. This paper reports on a case study in progress that highlights user engagement in the research process in relation to medical device development. To work with a specific group of medical device users to uncover unmet needs, translating these into design concepts, novel technologies and products. To validate a knowledge transfer model that may be replicated for a range of medical device applications and user groups. In depth qualitative case study to elicit and analyse user needs. The focus is on identifying design concepts for medical device applications from unmet needs, and validating these in an iterative feedback loop to the users. The case study has highlighted three interrelated challenges: ensuring unmet needs drive new design concepts and technology development; managing user expectations and managing the research process. Despite the challenges, active participation of users is crucial to developing usable and clinically effective devices.

A model of teaching and learning in the operating theatre.

PubMed

Lyon, Patricia

2004-12-01

This paper extends the work of an earlier publication by the same author which reported the findings of a case study designed to investigate how medical students learn and are taught in the operating theatre. The earlier paper was descriptive in nature, examining the challenges students face as learners in theatres. These were conceptualised around 3 key domains: the challenge posed by the physical environment; the challenge of the educational task, and the challenge of managing and negotiating a role as a participant in the professional workplace of theatres. This paper focuses exclusively on the third domain. It presents an interpretive model of teaching and learning in the operating theatre, drawing largely on conceptual frameworks developed within the literature on learning in work-based settings. A multimethod strategy included observation in theatres, interviews with students and surgeons, and a student survey. The themes that characterised the case were identified and the relationships among these themes were explored, leading to the development of the model. Symbolic interactionism provided the underlying theoretical framework. In any particular theatre session, the way in which learning evolves or is obstructed for any student, and the shape that teaching takes, depends on the interpretations that the student and the surgeon make in 'sizing up' the teaching and learning environment. How surgeons and students interpret and respond to each others' behaviour, style, attitude and even demeanour, has consequences for the way teaching and learning develop. The concepts of legitimacy and trust underpin these interpretations and are central to understanding the processes of teaching and learning in this setting.

Molecular modeling: An open invitation for applied mathematics

NASA Astrophysics Data System (ADS)

Mezey, Paul G.

2013-10-01

Molecular modeling methods provide a very wide range of challenges for innovative mathematical and computational techniques, where often high dimensionality, large sets of data, and complicated interrelations imply a multitude of iterative approximations. The physical and chemical basis of these methodologies involves quantum mechanics with several non-intuitive aspects, where classical interpretation and classical analogies are often misleading or outright wrong. Hence, instead of the everyday, common sense approaches which work so well in engineering, in molecular modeling one often needs to rely on rather abstract mathematical constraints and conditions, again emphasizing the high level of reliance on applied mathematics. Yet, the interdisciplinary aspects of the field of molecular modeling also generates some inertia and perhaps too conservative reliance on tried and tested methodologies, that is at least partially caused by the less than up-to-date involvement in the newest developments in applied mathematics. It is expected that as more applied mathematicians take up the challenge of employing the latest advances of their field in molecular modeling, important breakthroughs may follow. In this presentation some of the current challenges of molecular modeling are discussed.

X-1 to X-Wings: Developing a Parametric Cost Model

NASA Technical Reports Server (NTRS)

Sterk, Steve; McAtee, Aaron

2015-01-01

In todays cost-constrained environment, NASA needs an X-Plane database and parametric cost model that can quickly provide rough order of magnitude predictions of cost from initial concept to first fight of potential X-Plane aircraft. This paper takes a look at the steps taken in developing such a model and reports the results. The challenges encountered in the collection of historical data and recommendations for future database management are discussed. A step-by-step discussion of the development of Cost Estimating Relationships (CERs) is then covered.

Pathology resident and fellow education in a time of disruptive technologies.

PubMed

Ziai, James M; Smith, Brian R

2012-12-01

The development of disruptive technologies is changing the practice of pathology. Their implementation challenges traditional educational paradigms. Training programs must adapt to these heuristic needs. The dual explosion of new medical knowledge and innovative methodologies adds new practice aspects to the pathologist's areas of expertise. This transformation potentially challenges the traditional core model of training. It raises questions as to how pathology should incorporate future expanding subspecialty needs into educational and practice models. This article examines the impact of these disruptive technologies on resident and fellow education and explores alternative educational and practice models that may better accommodate pathology's future. Copyright © 2012 Elsevier Inc. All rights reserved.

Future Asian Education: The Challenge of Numbers.

ERIC Educational Resources Information Center

Adiseshiah, Malcolm S.

1980-01-01

Probes educational problems and needs in the developing nations of Asia. The major problems are overpopulation, poor educational facilities in rural areas, insufficient financial resources, inappropriate educational models and objectives, and unrealistically high expectations. More recent educational models stress equalizing educational access and…

Multi-Cone Model for Estimating GPS Ionospheric Delays

NASA Technical Reports Server (NTRS)

Sparks, Lawrence; Komjathy, Attila; Mannucci, Anthony

2009-01-01

The multi-cone model is a computational model for estimating ionospheric delays of Global Positioning System (GPS) signals. It is a direct descendant of the conical-domain model. A primary motivation for the development of this model is the need to find alternatives for modeling slant delays at low latitudes, where ionospheric behavior poses an acute challenge for GPS signal-delay estimates based upon the thin-shell model of the ionosphere.

Recommended Research Directions for Improving the Validation of Complex Systems Models.

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

Vugrin, Eric D.; Trucano, Timothy G.; Swiler, Laura Painton

Improved validation for models of complex systems has been a primary focus over the past year for the Resilience in Complex Systems Research Challenge. This document describes a set of research directions that are the result of distilling those ideas into three categories of research -- epistemic uncertainty, strong tests, and value of information. The content of this document can be used to transmit valuable information to future research activities, update the Resilience in Complex Systems Research Challenge's roadmap, inform the upcoming FY18 Laboratory Directed Research and Development (LDRD) call and research proposals, and facilitate collaborations between Sandia and externalmore » organizations. The recommended research directions can provide topics for collaborative research, development of proposals, workshops, and other opportunities.« less

A systematic review of the challenges to implementation of the patient-centred medical home: lessons for Australia.

PubMed

Janamian, Tina; Jackson, Claire L; Glasson, Nicola; Nicholson, Caroline

2014-08-04

To review the available literature to identify the major challenges and barriers to implementation and adoption of the patient-centred medical home (PCMH) model, topical in current Australian primary care reforms. Systematic review of peer-reviewed literature. PubMed and Embase databases were searched in December 2012 for studies published in English between January 2007 and December 2012. Studies of any type were included if they defined PCMH using the Patient-Centered Primary Care Collaborative Joint Principles, and reported data on challenges and barriers to implementation and adoption of the PCMH model. One researcher with content knowledge in the area abstracted data relating to the review objective and study design from eligible articles. A second researcher reviewed the abstracted data alongside the original article to check for accuracy and completeness. Thematic synthesis was used to in three stages: free line-by-line coding of data; organisation of "free codes" into related areas to construct "descriptive" themes and develop "analytical" themes. The main barriers identified related to: challenges with the transformation process; difficulties associated with change management; challenges in implementing and using an electronic health record that administers principles of PCMH; challenges with funding and appropriate payment models; insufficient resources and infrastructure within practices; and inadequate measures of performance. This systematic review documents the key challenges and barriers to implementing the PCMH model in United States family practice. It provides valuable evidence for Australian clinicians, policymakers, and organisations approaching adoption of PCMH elements within reform initiatives in this country.

Terrestrial Planet Finder Coronagraph Observatory summary

NASA Technical Reports Server (NTRS)

Ford, Virginia; Levine-Westa, Marie; Kissila, Andy; Kwacka, Eug; Hoa, Tim; Dumonta, Phil; Lismana, Doug; Fehera, Peter; Cafferty, Terry

2005-01-01

Creating an optical space telescope observatory capable of detecting and characterizing light from extra-solar terrestrial planets poses technical challenges related to extreme wavefront stability. The Terrestrial Planet Finder Coronagraph design team has been developing an observatory based on trade studies, modeling and analysis that has guided us towards design choices to enable this challenging mission. This paper will describe the current flight baseline design of the observatory and the trade studies that have been performed. The modeling and analysis of this design will be described including predicted performance and the tasks yet to be done.

Modeling and simulation challenges pursued by the Consortium for Advanced Simulation of Light Water Reactors (CASL)

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

Turinsky, Paul J., E-mail: turinsky@ncsu.edu; Kothe, Douglas B., E-mail: kothe@ornl.gov

The Consortium for the Advanced Simulation of Light Water Reactors (CASL), the first Energy Innovation Hub of the Department of Energy, was established in 2010 with the goal of providing modeling and simulation (M&S) capabilities that support and accelerate the improvement of nuclear energy's economic competitiveness and the reduction of spent nuclear fuel volume per unit energy, and all while assuring nuclear safety. To accomplish this requires advances in M&S capabilities in radiation transport, thermal-hydraulics, fuel performance and corrosion chemistry. To focus CASL's R&D, industry challenge problems have been defined, which equate with long standing issues of the nuclear powermore » industry that M&S can assist in addressing. To date CASL has developed a multi-physics “core simulator” based upon pin-resolved radiation transport and subchannel (within fuel assembly) thermal-hydraulics, capitalizing on the capabilities of high performance computing. CASL's fuel performance M&S capability can also be optionally integrated into the core simulator, yielding a coupled multi-physics capability with untapped predictive potential. Material models have been developed to enhance predictive capabilities of fuel clad creep and growth, along with deeper understanding of zirconium alloy clad oxidation and hydrogen pickup. Understanding of corrosion chemistry (e.g., CRUD formation) has evolved at all scales: micro, meso and macro. CFD R&D has focused on improvement in closure models for subcooled boiling and bubbly flow, and the formulation of robust numerical solution algorithms. For multiphysics integration, several iterative acceleration methods have been assessed, illuminating areas where further research is needed. Finally, uncertainty quantification and data assimilation techniques, based upon sampling approaches, have been made more feasible for practicing nuclear engineers via R&D on dimensional reduction and biased sampling. Industry adoption of CASL's evolving M&S capabilities, which is in progress, will assist in addressing long-standing and future operational and safety challenges of the nuclear industry. - Highlights: • Complexity of physics based modeling of light water reactor cores being addressed. • Capability developed to help address problems that have challenged the nuclear power industry. • Simulation capabilities that take advantage of high performance computing developed.« less

PopGen Fishbowl: A Free Online Simulation Model of Microevolutionary Processes

ERIC Educational Resources Information Center

Jones, Thomas C.; Laughlin, Thomas F.

2010-01-01

Natural selection and other components of evolutionary theory are known to be particularly challenging concepts for students to understand. To help illustrate these concepts, we developed a simulation model of microevolutionary processes. The model features all the components of Hardy-Weinberg theory, with population size, selection, gene flow,…

Emergence of Tables as First-Graders Cope with Modelling Tasks

ERIC Educational Resources Information Center

Peled, Irit; Keisar, Einav

2015-01-01

In this action research, first-graders were challenged to cope with a sequence of modelling tasks involving an analysis of given situations and choices of mathematical tools. In the course of the sequence, they underwent a change in the nature of their problem-solving processes and developed modelling competencies. Moreover, during the task…

Deep learning for healthcare: review, opportunities and challenges.

PubMed

Miotto, Riccardo; Wang, Fei; Wang, Shuang; Jiang, Xiaoqian; Dudley, Joel T

2017-05-06

Gaining knowledge and actionable insights from complex, high-dimensional and heterogeneous biomedical data remains a key challenge in transforming health care. Various types of data have been emerging in modern biomedical research, including electronic health records, imaging, -omics, sensor data and text, which are complex, heterogeneous, poorly annotated and generally unstructured. Traditional data mining and statistical learning approaches typically need to first perform feature engineering to obtain effective and more robust features from those data, and then build prediction or clustering models on top of them. There are lots of challenges on both steps in a scenario of complicated data and lacking of sufficient domain knowledge. The latest advances in deep learning technologies provide new effective paradigms to obtain end-to-end learning models from complex data. In this article, we review the recent literature on applying deep learning technologies to advance the health care domain. Based on the analyzed work, we suggest that deep learning approaches could be the vehicle for translating big biomedical data into improved human health. However, we also note limitations and needs for improved methods development and applications, especially in terms of ease-of-understanding for domain experts and citizen scientists. We discuss such challenges and suggest developing holistic and meaningful interpretable architectures to bridge deep learning models and human interpretability. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Talent management best practices: how exemplary health care organizations create value in a down economy.

PubMed

Groves, Kevin S

2011-01-01

: Difficult economic conditions and powerful workforce trends pose significant challenges to managing talent in health care organizations. Although robust research evidence supports the many benefits of maintaining a strong commitment to talent management practices despite these challenges, many organizations compound the problem by resorting to workforce reductions and limiting or eliminating investments in talent management. : This study examines how nationwide health care systems address these challenges through best practice talent management systems. Addressing important gaps in talent management theory and practice, this study develops a best practice model of talent management that is grounded in the contextual challenges facing health care practitioners. : Utilizing a qualitative case study that examined 15 nationwide health care systems, data were collected through semistructured interviews with 30 executives and document analysis of talent management program materials submitted by each organization. : Exemplary health care organizations employ a multiphased talent management system composed of six sequential phases and associated success factors that drive effective implementation. Based on these findings, a model of talent management best practices in health care organizations is presented. : Health care practitioners may utilize the best practice model to assess and enhance their respective talent management systems by establishing the business case for talent management, defining, identifying, and developing high-potential leaders, carefully communicating high-potential designations, and evaluating talent management outcomes.

Rewriting Professional Development: Professional Learning Communities in an Urban Charter School

ERIC Educational Resources Information Center

Glasheen, Gregory J.

2017-01-01

This study challenges traditional professional development models, in which teachers are positioned as receptacles for knowledge and "best practices". This type of professional development devalues the local knowledge teachers possess, their theories of practice (Lytle & Cochran-Smith, 1994), and their ability to reflect on their…

The Measure of Adolescent Heterosocial Competence: Development and Initial Validation

ERIC Educational Resources Information Center

Grover, Rachel L.; Nangle, Douglas W.; Zeff, Karen R.

2005-01-01

We developed and began construct validation of the Measure of Adolescent Heterosocial Competence (MAHC), a self-report instrument assessing the ability to negotiate effectively a range of challenging other-sex social interactions. Development followed the Goldfried and D'Zurilla (1969) behavioral-analytic model for assessing competence.…

Collaborative Outcome Measurement: Development of the Nationally Standardized Minimum Data Set

ERIC Educational Resources Information Center

Stephens, Barry C.; Kirchner, Corinne; Orr, Alberta L.; Suvino, Dawn; Rogers, Priscilla

2009-01-01

This article discusses the challenging process of developing a common data set for independent living programs serving older adults who are visually impaired. The three-year project, which included collaborative efforts among many stakeholders that encompass diverse program models, resulted in the development of the Internet-based Nationally…

A Motivational Theory of Life-Span Development

ERIC Educational Resources Information Center

Heckhausen, Jutta; Wrosch, Carsten; Schulz, Richard

2010-01-01

This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the…

Developing Culturally Responsive Teaching through Professional Noticing within Teacher Educator Modelling

ERIC Educational Resources Information Center

Averill, Robin; Anderson, Dayle; Drake, Michael

2015-01-01

Much evidence exists that culturally responsive and equitable teaching practices are challenging to develop. Evidence exists that in-the-moment coaching of "rehearsals" of practice can help foster mathematics teaching strategies, but how such coaching can assist the development of culturally responsive practice is less clear. Drawn from…

The social and political lives of zoonotic disease models: narratives, science and policy.

PubMed

Leach, Melissa; Scoones, Ian

2013-07-01

Zoonotic diseases currently pose both major health threats and complex scientific and policy challenges, to which modelling is increasingly called to respond. In this article we argue that the challenges are best met by combining multiple models and modelling approaches that elucidate the various epidemiological, ecological and social processes at work. These models should not be understood as neutral science informing policy in a linear manner, but as having social and political lives: social, cultural and political norms and values that shape their development and which they carry and project. We develop and illustrate this argument in relation to the cases of H5N1 avian influenza and Ebola, exploring for each the range of modelling approaches deployed and the ways they have been co-constructed with a particular politics of policy. Addressing the complex, uncertain dynamics of zoonotic disease requires such social and political lives to be made explicit in approaches that aim at triangulation rather than integration, and plural and conditional rather than singular forms of policy advice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Quiescent complement in nonhuman primates during E coli Shiga toxin-induced hemolytic uremic syndrome and thrombotic microangiopathy.

PubMed

Lee, Benjamin C; Mayer, Chad L; Leibowitz, Caitlin S; Stearns-Kurosawa, D J; Kurosawa, Shinichiro

2013-08-01

Enterohemorrhagic Escherichia coli (EHEC) produce ribosome-inactivating Shiga toxins (Stx1, Stx2) responsible for development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI). Some patients show complement activation during EHEC infection, raising the possibility of therapeutic targeting of complement for relief. Our juvenile nonhuman primate (Papio baboons) models of endotoxin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and AKI with glomerular thrombotic microangiopathy. There were no significant increases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) or Stx2 (n = 5) in plasma samples from T0 to euthanasia at 49.5 to 128 hours post-challenge. d-dimer and cell injury markers (HMGB1, histones) confirmed coagulopathy and cell injury. Thus, complement activation is not required for the development of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical models, and benefits or risks of complement inhibition should be studied further for this infection.

Solar Sail Roadmap Mission GN and C Challenges

NASA Technical Reports Server (NTRS)

Heaton, Andrew F.

2005-01-01

The NASA In-Space Propulsion program is funding development work for solar sails to enhance future scientific opportunities. Key to this effort are scientific solar sail roadmap missions identified by peer review. The two near-term missions of interest are L1 Diamond and Solar Polar Imager. Additionally, the New Millennium Program is sponsoring the Space Technology 9 (ST9) demonstration mission. Solar sails are one of five technologies competing for the ST9 flight demonstration. Two candidate solar sail missions have been identified for a potential ST9 flight. All the roadmap missions and candidate flight demonstration missions face various GN&C challenges. A variety of efforts are underway to address these challenges. These include control actuator design and testing, low thrust optimization studies, attitude control system design and modeling, control-structure interaction studies, trajectory control design, and solar radiation pressure model development. Here we survey the various efforts underway and identify a few of specific recent interest and focus.

Building Information Modelling: Challenges and Barriers in Implement of BIM for Interior Design Industry in Malaysia

NASA Astrophysics Data System (ADS)

Hamid, A. B. Abd; Taib, M. Z. Mohd; Razak, A. H. N. Abdul; Embi, M. R.

2018-04-01

Building Information Modelling (BIM) is an innovative approach that has developed crossways the global in architecture, engineering and construction (AEC) industry. The construction industry of Malaysia has undergone a rapid development and dynamic technology adoption in advance and methods between the players industry and stakeholders. Consequently, limited technologies and devices have not been successful as it should have been. This study will be emphasizing scenarios of challenges and barriers in adopting BIM in interior design industry in Malaysia. The study was emphasizing the challenges and barriers in BIM usage from the designer’s perspective. The data are collected through the questionnaires as to identifying the barriers, knowledge, readiness and awareness and distributed to interior design firms were selected randomly. The finding of this research is to examine the barriers and causes of variables BIM usage for interior design industry in Malaysia. The outcome of this study is to identify the constraint of adoption BIM in interior design industry compare to others players in same industry.

Anthrax vaccine antigen-adjuvant formulations completely protect New Zealand white rabbits against challenge with Bacillus anthracis Ames strain spores.

PubMed

Peachman, Kristina K; Li, Qin; Matyas, Gary R; Shivachandra, Sathish B; Lovchik, Julie; Lyons, Rick C; Alving, Carl R; Rao, Venigalla B; Rao, Mangala

2012-01-01

In an effort to develop an improved anthrax vaccine that shows high potency, five different anthrax protective antigen (PA)-adjuvant vaccine formulations that were previously found to be efficacious in a nonhuman primate model were evaluated for their efficacy in a rabbit pulmonary challenge model using Bacillus anthracis Ames strain spores. The vaccine formulations include PA adsorbed to Alhydrogel, PA encapsulated in liposomes containing monophosphoryl lipid A, stable liposomal PA oil-in-water emulsion, PA displayed on bacteriophage T4 by the intramuscular route, and PA mixed with Escherichia coli heat-labile enterotoxin administered by the needle-free transcutaneous route. Three of the vaccine formulations administered by the intramuscular or the transcutaneous route as a three-dose regimen induced 100% protection in the rabbit model. One of the formulations, liposomal PA, also induced significantly higher lethal toxin neutralizing antibodies than PA-Alhydrogel. Even 5 months after the second immunization of a two-dose regimen, rabbits vaccinated with liposomal PA were 100% protected from lethal challenge with Ames strain spores. In summary, the needle-free skin delivery and liposomal formulation that were found to be effective in two different animal model systems appear to be promising candidates for next-generation anthrax vaccine development.

Synthetic biology of cyanobacteria: unique challenges and opportunities

PubMed Central

Berla, Bertram M.; Saha, Rajib; Immethun, Cheryl M.; Maranas, Costas D.; Moon, Tae Seok; Pakrasi, Himadri B.

2013-01-01

Photosynthetic organisms, and especially cyanobacteria, hold great promise as sources of renewably-produced fuels, bulk and specialty chemicals, and nutritional products. Synthetic biology tools can help unlock cyanobacteria's potential for these functions, but unfortunately tool development for these organisms has lagged behind that for S. cerevisiae and E. coli. While these organisms may in many cases be more difficult to work with as “chassis” strains for synthetic biology than certain heterotrophs, the unique advantages of autotrophs in biotechnology applications as well as the scientific importance of improved understanding of photosynthesis warrant the development of these systems into something akin to a “green E. coli.” In this review, we highlight unique challenges and opportunities for development of synthetic biology approaches in cyanobacteria. We review classical and recently developed methods for constructing targeted mutants in various cyanobacterial strains, and offer perspective on what genetic tools might most greatly expand the ability to engineer new functions in such strains. Similarly, we review what genetic parts are most needed for the development of cyanobacterial synthetic biology. Finally, we highlight recent methods to construct genome-scale models of cyanobacterial metabolism and to use those models to measure properties of autotrophic metabolism. Throughout this paper, we discuss some of the unique challenges of a diurnal, autotrophic lifestyle along with how the development of synthetic biology and biotechnology in cyanobacteria must fit within those constraints. PMID:24009604

Multiphysics and multiscale modelling, data-model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics.

PubMed

Chabiniok, Radomir; Wang, Vicky Y; Hadjicharalambous, Myrianthi; Asner, Liya; Lee, Jack; Sermesant, Maxime; Kuhl, Ellen; Young, Alistair A; Moireau, Philippe; Nash, Martyn P; Chapelle, Dominique; Nordsletten, David A

2016-04-06

With heart and cardiovascular diseases continually challenging healthcare systems worldwide, translating basic research on cardiac (patho)physiology into clinical care is essential. Exacerbating this already extensive challenge is the complexity of the heart, relying on its hierarchical structure and function to maintain cardiovascular flow. Computational modelling has been proposed and actively pursued as a tool for accelerating research and translation. Allowing exploration of the relationships between physics, multiscale mechanisms and function, computational modelling provides a platform for improving our understanding of the heart. Further integration of experimental and clinical data through data assimilation and parameter estimation techniques is bringing computational models closer to use in routine clinical practice. This article reviews developments in computational cardiac modelling and how their integration with medical imaging data is providing new pathways for translational cardiac modelling.

Visualization, documentation, analysis, and communication of large scale gene regulatory networks

PubMed Central

Longabaugh, William J.R.; Davidson, Eric H.; Bolouri, Hamid

2009-01-01

Summary Genetic regulatory networks (GRNs) are complex, large-scale, and spatially and temporally distributed. These characteristics impose challenging demands on computational GRN modeling tools, and there is a need for custom modeling tools. In this paper, we report on our ongoing development of BioTapestry, an open source, freely available computational tool designed specifically for GRN modeling. We also outline our future development plans, and give some examples of current applications of BioTapestry. PMID:18757046

An adjuvant free mouse model of oral allergenic sensitization to rice seeds protein

PubMed Central

2011-01-01

Background Rice is commonly known as a staple crop consumed worldwide, though with several rice proteins being reported for allergic properties in clinical studies. Thus, there is a growing need for the development of an animal model to better understand the allergenicity of rice proteins and the immunological and pathophysiological mechanisms underlying the development of food allergy. Methods Groups of BALB/c mice were sensitized daily with freshly homogenized rice flour (30 mg or 80 mg) without adjuvant by intragastric gavage. In addition, the mice were challenged with extracted rice flour proteins at several time points intragastrically. Hypersensitivity symptoms in mice were evaluated according to a scoring system. Vascular leakage, ELISA of rice protein-specific IgE, histopathology of small intestine, and passive cutaneous anaphylaxis were conducted on challenged mice. Results An adjuvant free mouse model of rice allergy was established with sensitized mice showing increased scratching behaviors and increased vascular permeability. Rice protein-specific IgE was detected after eighteen days of sensitization and from the fifth challenge onwards. Inflammatory damage to the epithelium in the small intestine of mice was observed beyond one month of sensitization. Passive cutaneous anaphylaxis results confirmed the positive rice allergy in the mouse model. Conclusions We introduced a BALB/c mouse model of rice allergy with simple oral sensitization without the use of adjuvant. This model would serve as a useful tool for further analysis on the immunopathogenic mechanisms of the various rice allergens, for the evaluation of the hypersensitivity of rice or other cereal grains, and to serve as a platform for the development of immunotherapies against rice allergens. PMID:21605393

A new model of diabetic nephropathy in C57BL/6 mice challenged with advanced oxidation protein products.

PubMed

Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Xu, Liting; Wan, Jiao; Liu, Youhua

2018-04-01

There remains a lack of robust mouse models with key features of advanced human diabetic nephropathy (DN). Few options of murine models of DN require mutations to be superimposed to obtain desired phenotypic characteristics. Most genetically modified mice are on the C57BL/6 background; however, they are notorious for resistance to develop DN. To overcome these conundrums, this study reports a novel DN model by challenging with advanced oxidation protein products (AOPPs) in streptozotocin-induced diabetic C57BL/6 mice. AOPPs-challenged diabetic C57BL/6 mice were more sensitive to develop progressive proteinuria, causing a 5.59-fold increase in urine albumin to creatinine ratio as compared to diabetic controls by 24 weeks. Typical lesions were present as demonstrated by significant diffuse mesangial expansion, diffuse podocyte foot process effacement, increased glomerular basement membrane thickness, focal arteriolar hyalinosis, mesangiolysis, and mild interstitial fibrosis. These changes were alleviated by losartan treatment. Collectively, these results suggest that AOPPs can accelerate the progression of DN in the resistant C57BL/6 mouse strain. Our studies offer a novel model for studying the pathogenesis of DN that resembles human diabetic kidney disease. It also makes it possible to interrogate the role of specific genetic modifications and to evaluate novel therapeutics to treat DN in preclinical setting. Copyright © 2018. Published by Elsevier Inc.

Companies Claim to Fame and their scientific challenges in vaccine development.

PubMed

Boon, Louis

2009-02-21

Although basic scientific immunological knowledge is the foundation for the development of novel vaccination approaches, beyond proof of concept in animal models, translational scientific immunological efforts are obligatory for successful development of a vaccine for use in humans. Translational technology is developed/used by biotechnology companies to generate better, safer or cheaper vaccines. Their proprietary position and/or proprietary technology are the basis of services that they offer to other companies or for products that they develop themselves. Some of the translational challenges are described in this review. In addition, a number of novel technologies developed by several biotechnology companies in The Netherlands are described. This document however, is far from complete and highlights only a small part of it.

Data Logging and Data Modelling: Using seismology and seismic data to create challenge in the academic classroom.

NASA Astrophysics Data System (ADS)

Neighbour, Gordon

2013-04-01

In 2012 Computing and Information Technology was disapplied from the English National Curriculum and therefore no longer has a compulsory programme of study. Data logging and data modelling are still essential components of the curriculum in the Computing and Information Technology classroom. Once the students have mastered the basics of both spreadsheet and information handling software they need to be further challenged. All too often the data used with relation to data-logging and data-handling is not realistic enough to really challenge very able students. However, using data from seismology allows students to manipulate "real" data and enhances their experience of geo-science, developing their skills and then allowing them to build on this work in both the science and geography classroom. This new scheme of work "Seismology at School" has allowed the students to work and develop skills beyond those normally expected for their age group and has allowed them to better appreciate their learning experience of "Natural Hazards" in the science and geography classroom in later years. The students undertake research to help them develop their understanding of earthquakes. This includes using materials from other nations within the European Economic Area, to also develop and challenge their use of Modern Foreign Languages. They are then challenged to create their own seismometers using simple kits and 'free' software - this "problem-solving" approach to their work is designed to enhance team-work and to extend the challenge they experience in the classroom. The students are then are asked to manipulate a "real" set of data using international earthquake data from the most recent whole year. This allows the students to make use of many of the analytical and statistical functions of both spreadsheet software and information handling software in a meaningful way. The students will need to have developed a hypothesis which their work should have provided either validation for or against. They are required to document their progress throughout the project and submit their work as an electronic portfolio for marking and this thus challenges their organisational abilities. Finally through the project it is hoped to develop and extend partnerships with other schools in the European Economic Area so that the students are able to work with students from these areas to further appreciate the teaching of "Natural Hazards" in other cultures within the EEA.

Teacher and student supports for implementation of the NGSS

NASA Astrophysics Data System (ADS)

Severance, Samuel

Through three articles, this dissertation examines the use of supports for implementing the Next Generation Science Standards (NGSS) within a large urban school district. Article one, titled Organizing for Teacher Agency in Curricular Co-design, examines the need for coherent curriculum materials that teachers' had a meaningful role in shaping and how the use of a co-design approach and specific tools and routines can help to address this need. Article two, titled Relevant Learning and Student Agency within a Citizen Science Design Challenge, examines the need for curriculum materials that provide students with learning experiences they find relevant and that expands their sense of agency and how a curriculum centered around a community-based citizen science design challenge can help achieve such an aim. Article three, titled Implementation of a Novel Professional Development Program to Support Teachers' Understanding of Modeling, examines the need for professional development that builds teachers' understanding of and skill in engaging their students in the practice of developing and using models and how a novel professional development program, the Next Generation Science Exemplar, can aid teachers in this regard by providing them with carefully sequenced professional development activities and specific modeling tools for use in the classroom.

A change roadmap towards research paradigm in low-resource countries: retinoblastoma model in Egypt.

PubMed

Alfaar, Ahmad Samir; Nour, Radwa; Bakry, Mohamed Sabry; Kamal, Mohamed; Hassanain, Omneya; Labib, Rania M; Rashed, Wafaa M; Elzomor, Hossam; Alieldin, Adel; Taha, Hala; Zaghloul, Mohamed Saad; Ezzat, Sameera; AboElnaga, Sherif

2017-02-01

Research on childhood diseases represents a great global challenge. This challenge is maximized in both childhood cancer disciplines and developing world. In this paper, we aim at describing our institution experience in starting a structured childhood cancer research program in one of the developing countries in a short time based on philanthropic efforts. We used retinoblastoma as an example for what was conducted in this program. Starting in 2008, this program included improving clinical practice and its related supporting services besides developing new research services that both complement the clinical activities and pave the way towards creating a research foundation in the country. Results included developing hospital standard treatment protocols, developing national clinical trials, joining international consortia for childhood cancers clinical trials, developing data collection tools and real-time analytics, establishing a biobanking facility, and developing highly qualified team for conducting clinical, epidemiologic, and translational research studies. Moreover, this effort resulted in improving both clinical practice and patients' awareness nationally. This model can be used for other startup facilities that aim at finding answers for their national health problems in low-resource setting.

A suite of benchmark and challenge problems for enhanced geothermal systems

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

White, Mark; Fu, Pengcheng; McClure, Mark

A diverse suite of numerical simulators is currently being applied to predict or understand the performance of enhanced geothermal systems (EGS). To build confidence and identify critical development needs for these analytical tools, the United States Department of Energy, Geothermal Technologies Office sponsored a Code Comparison Study (GTO-CCS), with participants from universities, industry, and national laboratories. A principal objective for the study was to create a community forum for improvement and verification of numerical simulators for EGS modeling. Teams participating in the study were those representing U.S. national laboratories, universities, and industries, and each team brought unique numerical simulation capabilitiesmore » to bear on the problems. Two classes of problems were developed during the study, benchmark problems and challenge problems. The benchmark problems were structured to test the ability of the collection of numerical simulators to solve various combinations of coupled thermal, hydrologic, geomechanical, and geochemical processes. This class of problems was strictly defined in terms of properties, driving forces, initial conditions, and boundary conditions. The challenge problems were based on the enhanced geothermal systems research conducted at Fenton Hill, near Los Alamos, New Mexico, between 1974 and 1995. The problems involved two phases of research, stimulation, development, and circulation in two separate reservoirs. The challenge problems had specific questions to be answered via numerical simulation in three topical areas: 1) reservoir creation/stimulation, 2) reactive and passive transport, and 3) thermal recovery. Whereas the benchmark class of problems were designed to test capabilities for modeling coupled processes under strictly specified conditions, the stated objective for the challenge class of problems was to demonstrate what new understanding of the Fenton Hill experiments could be realized via the application of modern numerical simulation tools by recognized expert practitioners. We present the suite of benchmark and challenge problems developed for the GTO-CCS, providing problem descriptions and sample solutions.« less

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: development of a prognostic model through a crowdsourced challenge with open clinical trial data

PubMed Central

Guinney, Justin; Wang, Tao; Laajala, Teemu D; Winner, Kimberly Kanigel; Bare, J Christopher; Neto, Elias Chaibub; Khan, Suleiman A; Peddinti, Gopal; Airola, Antti; Pahikkala, Tapio; Mirtti, Tuomas; Yu, Thomas; Bot, Brian M; Shen, Liji; Abdallah, Kald; Norman, Thea; Friend, Stephen; Stolovitzky, Gustavo; Soule, Howard; Sweeney, Christopher J; Ryan, Charles J; Scher, Howard I; Sartor, Oliver; Xie, Yang; Aittokallio, Tero; Zhou, Fang Liz; Costello, James C

2016-01-01

Summary Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest—namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial—ENTHUSE M1—in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0·791; Bayes factor >5) and surpassed the reference model (iAUC 0·743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3·32, 95% CI 2·39–4·62, p<0·0001; reference model: 2·56, 1·85–3·53, p<0·0001). The new model was validated further on the ENTHUSE M1 cohort with similarly high performance (iAUC 0·768). Meta-analysis across all methods confirmed previously identified predictive clinical variables and revealed aspartate aminotransferase as an important, albeit previously under-reported, prognostic biomarker. Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer. Funding Sanofi US Services, Project Data Sphere. PMID:27864015

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: development of a prognostic model through a crowdsourced challenge with open clinical trial data.

PubMed

Guinney, Justin; Wang, Tao; Laajala, Teemu D; Winner, Kimberly Kanigel; Bare, J Christopher; Neto, Elias Chaibub; Khan, Suleiman A; Peddinti, Gopal; Airola, Antti; Pahikkala, Tapio; Mirtti, Tuomas; Yu, Thomas; Bot, Brian M; Shen, Liji; Abdallah, Kald; Norman, Thea; Friend, Stephen; Stolovitzky, Gustavo; Soule, Howard; Sweeney, Christopher J; Ryan, Charles J; Scher, Howard I; Sartor, Oliver; Xie, Yang; Aittokallio, Tero; Zhou, Fang Liz; Costello, James C

2017-01-01

Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0·791; Bayes factor >5) and surpassed the reference model (iAUC 0·743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3·32, 95% CI 2·39-4·62, p<0·0001; reference model: 2·56, 1·85-3·53, p<0·0001). The new model was validated further on the ENTHUSE M1 cohort with similarly high performance (iAUC 0·768). Meta-analysis across all methods confirmed previously identified predictive clinical variables and revealed aspartate aminotransferase as an important, albeit previously under-reported, prognostic biomarker. Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer. Sanofi US Services, Project Data Sphere. Copyright © 2017 Elsevier Ltd. All rights reserved.

Simulating the impacts of disturbances on forest carbon cycling in North America: Processes, data, models, and challenges

USGS Publications Warehouse

Liu, Shuguang; Bond-Lamberty, Ben; Hicke, Jeffrey A.; Vargas, Rodrigo; Zhao, Shuqing; Chen, Jing; Edburg, Steven L.; Hu, Yueming; Liu, Jinxun; McGuire, A. David; Xiao, Jingfeng; Keane, Robert; Yuan, Wenping; Tang, Jianwu; Luo, Yiqi; Potter, Christopher; Oeding, Jennifer

2011-01-01

Forest disturbances greatly alter the carbon cycle at various spatial and temporal scales. It is critical to understand disturbance regimes and their impacts to better quantify regional and global carbon dynamics. This review of the status and major challenges in representing the impacts of disturbances in modeling the carbon dynamics across North America revealed some major advances and challenges. First, significant advances have been made in representation, scaling, and characterization of disturbances that should be included in regional modeling efforts. Second, there is a need to develop effective and comprehensive process‐based procedures and algorithms to quantify the immediate and long‐term impacts of disturbances on ecosystem succession, soils, microclimate, and cycles of carbon, water, and nutrients. Third, our capability to simulate the occurrences and severity of disturbances is very limited. Fourth, scaling issues have rarely been addressed in continental scale model applications. It is not fully understood which finer scale processes and properties need to be scaled to coarser spatial and temporal scales. Fifth, there are inadequate databases on disturbances at the continental scale to support the quantification of their effects on the carbon balance in North America. Finally, procedures are needed to quantify the uncertainty of model inputs, model parameters, and model structures, and thus to estimate their impacts on overall model uncertainty. Working together, the scientific community interested in disturbance and its impacts can identify the most uncertain issues surrounding the role of disturbance in the North American carbon budget and develop working hypotheses to reduce the uncertainty

A high-resolution global flood hazard model

NASA Astrophysics Data System (ADS)

Sampson, Christopher C.; Smith, Andrew M.; Bates, Paul B.; Neal, Jeffrey C.; Alfieri, Lorenzo; Freer, Jim E.

2015-09-01

Floods are a natural hazard that affect communities worldwide, but to date the vast majority of flood hazard research and mapping has been undertaken by wealthy developed nations. As populations and economies have grown across the developing world, so too has demand from governments, businesses, and NGOs for modeled flood hazard data in these data-scarce regions. We identify six key challenges faced when developing a flood hazard model that can be applied globally and present a framework methodology that leverages recent cross-disciplinary advances to tackle each challenge. The model produces return period flood hazard maps at ˜90 m resolution for the whole terrestrial land surface between 56°S and 60°N, and results are validated against high-resolution government flood hazard data sets from the UK and Canada. The global model is shown to capture between two thirds and three quarters of the area determined to be at risk in the benchmark data without generating excessive false positive predictions. When aggregated to ˜1 km, mean absolute error in flooded fraction falls to ˜5%. The full complexity global model contains an automatically parameterized subgrid channel network, and comparison to both a simplified 2-D only variant and an independently developed pan-European model shows the explicit inclusion of channels to be a critical contributor to improved model performance. While careful processing of existing global terrain data sets enables reasonable model performance in urban areas, adoption of forthcoming next-generation global terrain data sets will offer the best prospect for a step-change improvement in model performance.

Update - Concept of Operations for Integrated Model-Centric Engineering at JPL

NASA Technical Reports Server (NTRS)

Bayer, Todd J.; Bennett, Matthew; Delp, Christopher L.; Dvorak, Daniel; Jenkins, Steven J.; Mandutianu, Sanda

2011-01-01

The increasingly ambitious requirements levied on JPL's space science missions, and the development pace of such missions, challenge our current engineering practices. All the engineering disciplines face this growth in complexity to some degree, but the challenges are greatest in systems engineering where numerous competing interests must be reconciled and where complex system level interactions must be identified and managed. Undesired system-level interactions are increasingly a major risk factor that cannot be reliably exposed by testing, and natural-language single-viewpoint specifications areinadequate to capture and expose system level interactions and characteristics. Systems engineering practices must improve to meet these challenges, and the most promising approach today is the movement toward a more integrated and model-centric approach to mission conception, design, implementation and operations. This approach elevates engineering models to a principal role in systems engineering, gradually replacing traditional document centric engineering practices.

P-8A Poseidon strategy for modeling & simulation verification validation & accreditation (VV&A)

NASA Astrophysics Data System (ADS)

Kropp, Derek L.

2009-05-01

One of the first challenges in addressing the need for Modeling & Simulation (M&S) Verification, Validation, & Accreditation (VV&A) is to develop an approach for applying structured and formalized VV&A processes. The P-8A Poseidon Multi-Mission Maritime Aircraft (MMA) Program Modeling and Simulation Accreditation Strategy documents the P-8A program's approach to VV&A. The P-8A strategy tailors a risk-based approach and leverages existing bodies of knowledge, such as the Defense Modeling and Simulation Office Recommended Practice Guide (DMSO RPG), to make the process practical and efficient. As the program progresses, the M&S team must continue to look for ways to streamline the process, add supplemental steps to enhance the process, and identify and overcome procedural, organizational, and cultural challenges. This paper includes some of the basics of the overall strategy, examples of specific approaches that have worked well, and examples of challenges that the M&S team has faced.

Strategically Planning to Change

ERIC Educational Resources Information Center

Atkins, Kemal

2010-01-01

Higher education, like the private sector, is searching for innovative ways to respond to demographic shifts, globalization, greater accountability, and new technologies. New organizational models are needed to meet these challenges. In a rapidly changing world, the development of such models can occur through effective strategic analysis and…

Application of Signaling Pathway-Based Adverse Outcome Pathways and High Throughput Toxicokinetic-PBPK for Developmental Cardiac Malformations

EPA Science Inventory

Associating putative molecular initiating events (MIE) with downstream cell signaling pathways and modeling fetal exposure kinetics is an important challenge for integration in developmental systems toxicology. Here, we describe an integrative systems toxicology model for develop...

New Consortial Model for E-Books Acquisitions

ERIC Educational Resources Information Center

Swindler, Luke

2016-01-01

E-books constitute major challenges for library collections generally and present fundamental problems for consortial collection development specifically. The Triangle Research Libraries Network (TRLN) and Oxford University Press (OUP) have created a mutually equitable and financially sustainable model for the consortial acquisition of e-books…

A Nitrogen Physical Input-Output Table (PIOT) Model for Illinois

EPA Science Inventory

Nitrogen (N) presents an important challenge for sustainability due to its role in providing goods and services to society, since release of N beyond its intended use has many negative consequences. Several systems modeling approaches have been developed to understand the tradeof...

Challenges in soil erosion research and prediction model development

USDA-ARS?s Scientific Manuscript database

Quantification of soil erosion has been traditionally considered as a surface hydrologic process with equations for soil detachment and sediment transport derived from the mechanics and hydraulics of the rainfall and surface flow. Under the current erosion modeling framework, the soil has a constant...

Developing a global model of magnetospheric substorms

NASA Astrophysics Data System (ADS)

Kan, J. R.

1990-09-01

Competing models of magnetospheric substorms are discussed. The definitions of the three substorm phases are presented, and the advantages and drawbacks of the near-earth X-line model, magnetosphere-ionosphere coupling model, low-latitude boundary layer model, and thermal catastrophe model are examined. It is shown that the main challenge to achieving a quantitative understanding of the magnetospheric signatures of substorms is to understand the anomalous dissipation processes in collisionless plasmas.

Research advances and challenges in one-dimensional modeling of secondary settling tanks--a critical review.

PubMed

Li, Ben; Stenstrom, M K

2014-11-15

Sedimentation is one of the most important processes that determine the performance of the activated sludge process (ASP), and secondary settling tanks (SSTs) have been frequently investigated with the mathematical models for design and operation optimization. Nevertheless their performance is often far from satisfactory. The starting point of this paper is a review of the development of settling theory, focusing on batch settling and the development of flux theory, since they played an important role in the early stage of SST investigation. The second part is an explicit review of the established 1-D SST models, including the relevant physical law, various settling behaviors (hindered, transient, and compression settling), the constitutive functions, and their advantages and disadvantages. The third part is a discussion of numerical techniques required to solve the governing equation, which is usually a partial differential equation. Finally, the most important modeling challenges, such as settleability description, settling behavior understanding, are presented. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improving and Accelerating Drug Development for Nervous System Disorders

PubMed Central

Pankevich, Diana E.; Altevogt, Bruce M.; Dunlop, John; Gage, Fred H.; Hyman, Steve E.

2014-01-01

Advances in the neurosciences have placed the field in the position where it is poised to significantly reduce the burden of nervous system disorders. However, drug discovery, development and translation for nervous system disorders still pose many unique challenges. The key scientific challenges can be summarized as follows: mechanisms of disease, target identification and validation, predictive models, biomarkers for patient stratification and as endpoints for clinical trials, clear regulatory pathways, reliability and reproducibility of published data, and data sharing and collaboration. To accelerate nervous system drug development the Institute of Medicine’s Forum on Neuroscience and Nervous System Disorders has hosted a series of public workshops that brought together representatives of industry, government (including both research funding and regulatory agencies), academia, and patient groups to discuss these challenges and offer potential strategies to improve the translational neuroscience. PMID:25442933

Nuclear Explosion Monitoring Advances and Challenges

NASA Astrophysics Data System (ADS)

Baker, G. E.

2015-12-01

We address the state-of-the-art in areas important to monitoring, current challenges, specific efforts that illustrate approaches addressing shortcomings in capabilities, and additional approaches that might be helpful. The exponential increase in the number of events that must be screened as magnitude thresholds decrease presents one of the greatest challenges. Ongoing efforts to exploit repeat seismic events using waveform correlation, subspace methods, and empirical matched field processing holds as much "game-changing" promise as anything being done, and further efforts to develop and apply such methods efficiently are critical. Greater accuracy of travel time, signal loss, and full waveform predictions are still needed to better locate and discriminate seismic events. Important developments include methods to model velocities using multiple types of data; to model attenuation with better separation of source, path, and site effects; and to model focusing and defocusing of surface waves. Current efforts to model higher frequency full waveforms are likely to improve source characterization while more effective estimation of attenuation from ambient noise holds promise for filling in gaps. Censoring in attenuation modeling is a critical problem to address. Quantifying uncertainty of discriminants is key to their operational use. Efforts to do so for moment tensor (MT) inversion are particularly important, and fundamental progress on the statistics of MT distributions is the most important advance needed in the near term in this area. Source physics is seeing great progress through theoretical, experimental, and simulation studies. The biggest need is to accurately predict the effects of source conditions on seismic generation. Uniqueness is the challenge here. Progress will depend on studies that probe what distinguishes mechanisms, rather than whether one of many possible mechanisms is consistent with some set of observations.

Anisakis simplex allergy: a murine model of anaphylaxis induced by parasitic proteins displays a mixed Th1/Th2 pattern

PubMed Central

Baeza, M L; Conejero, L; Higaki, Y; Martín, E; Pérez, C; Infante, S; Rubio, M; Zubeldia, J M

2005-01-01

The study of the singular hypersensitivity reactions to Anisakis simplex (A.s) proteins, may help us to undestand many of the unknown immune interactions between helmiths infections and allergy. We have developed a murine model of allergy to A. simplex, that mimics human A. simplex allergy to study the specific aspects of anaphylaxis induced by parasites. Male C3H/HeJ mice were intraperitoneally sensitized to A. simplex. Mice were then intravenous or orally challenged with A. simplex. Antigen-specific immunoglobulins, polyclonal IgE, anaphylactic symptoms, plasma histamine levels and cytokine profiles were determined. Comparative IgE immunoblot analyses were also performed. Specific IgE, IgG1 and IgG2a were detected in sensitized mice since week 3. Polyclonal IgE raised and peaked with different kinetics. Intravenous A. simplex challenge produced anaphylaxis in mice, accompanied by plasma histamine release. Oral A. simplex challenge in similarly sensitized mice did not caused symptoms nor histamine release. Numerous A. simplex allergens were recognized by sensitized mouse sera, some of them similar to human serum. The A. simplex stimulated splenocytes released IL-10, IFN-γ, IL-4, IL-13 and IL-5. We describe a new animal model of anaphylaxis. It exhibits characteristics of type I hypersensitivity reactions to Anisakis simplex similar to those observed in allergic humans. Different responses to i.v. or oral A. simplex challenges emerged, which did not reflect a window tolerization period. The cytokine profile developed (mixed Th1/Th2 pattern) differed from the observed in classical models of anaphylaxis or allergy to food antigens. This model may permit to investigate the peculiar allergic reactions to parasitic proteins. PMID:16297154

EPOS: Integrating seismological Research Infrastructures within Europe

NASA Astrophysics Data System (ADS)

Eck Van, Torild; Clinton, John; Haslinger, Florian; Michelini, Alberto

2013-04-01

Seismological data, products and models are currently produced in Europe within individual countries or research organizations, and with the contribution of coordinating organizations like ORFEUS and EMSC. In spite of these partly scattered resources, significant scientific results are obtained, excellent monitoring and information systems are operational and a huge amount of research quality data is being archived and disseminated. The seismological community, however, realizes that an effective European-scale integration of seismological and related geophysical data, products and models, combined with broad and easy access, is needed to facilitate future top level geoscience, for example, to appropriately harness the technological advancements enabling large scale and near-real time data processing. Here we present the technical concepts and developments within European seismology that will build the next generation of integrated services. Within the EPOS initiative and a number of related projects, where seismology infrastructure and IT developments are merging, in depth discussions are on-going on how to realize an effective integration. Concepts and visions addressing the obviously complex challenges resulting from the current highly distributed facilities and resources in Europe are emerging and are already partly being implemented. We will provide an overview of developments within key EU projects (NERA, VERCE, COOPEUS, EUDAT, REAKT, COMMIT, etc) and demonstrate how these are in coherence with EPOS and other on-going global initiatives. Within seismology current focus is on addressing IT related challenges to a) organize distributed data archives, develop metadata attributes for improved data searching, specifically including quality indicators, and define products from data and/or models, and b) define and create(on-line) monitoring, data access and processing tools. While developments to meet those challenges originate partly from within the community itself, it is important to harvest relevant ideas and tools from other scientific communities dealing with similar issues. We will present a short summary of those developments and how they fit within the proposed visions and concepts. These integration developments address a wide framework of seismological services that include: basic seismological data services (waveform data from velocity and acceleration sensors from land and underwater sites); seismological data products (source mechanism and process estimates, earthquake catalogues, structural and tomography model estimations); seismological models (synthetic waveforms, earth and earthquake source models, hazard models).Our aim is to build significantlyimproved seismological services and valuable products for multidisciplinary earth science research.

Moving beyond regression techniques in cardiovascular risk prediction: applying machine learning to address analytic challenges

PubMed Central

Goldstein, Benjamin A.; Navar, Ann Marie; Carter, Rickey E.

2017-01-01

Abstract Risk prediction plays an important role in clinical cardiology research. Traditionally, most risk models have been based on regression models. While useful and robust, these statistical methods are limited to using a small number of predictors which operate in the same way on everyone, and uniformly throughout their range. The purpose of this review is to illustrate the use of machine-learning methods for development of risk prediction models. Typically presented as black box approaches, most machine-learning methods are aimed at solving particular challenges that arise in data analysis that are not well addressed by typical regression approaches. To illustrate these challenges, as well as how different methods can address them, we consider trying to predicting mortality after diagnosis of acute myocardial infarction. We use data derived from our institution's electronic health record and abstract data on 13 regularly measured laboratory markers. We walk through different challenges that arise in modelling these data and then introduce different machine-learning approaches. Finally, we discuss general issues in the application of machine-learning methods including tuning parameters, loss functions, variable importance, and missing data. Overall, this review serves as an introduction for those working on risk modelling to approach the diffuse field of machine learning. PMID:27436868

Application of Mortar Coupling in Multiscale Modelling of Coupled Flow, Transport, and Biofilm Growth in Porous Media

NASA Astrophysics Data System (ADS)

Laleian, A.; Valocchi, A. J.; Werth, C. J.

2017-12-01

Multiscale models of reactive transport in porous media are capable of capturing complex pore-scale processes while leveraging the efficiency of continuum-scale models. In particular, porosity changes caused by biofilm development yield complex feedbacks between transport and reaction that are difficult to quantify at the continuum scale. Pore-scale models, needed to accurately resolve these dynamics, are often impractical for applications due to their computational cost. To address this challenge, we are developing a multiscale model of biofilm growth in which non-overlapping regions at pore and continuum spatial scales are coupled with a mortar method providing continuity at interfaces. We explore two decompositions of coupled pore-scale and continuum-scale regions to study biofilm growth in a transverse mixing zone. In the first decomposition, all reaction is confined to a pore-scale region extending the transverse mixing zone length. Only solute transport occurs in the surrounding continuum-scale regions. Relative to a fully pore-scale result, we find the multiscale model with this decomposition has a reduced run time and consistent result in terms of biofilm growth and solute utilization. In the second decomposition, reaction occurs in both an up-gradient pore-scale region and a down-gradient continuum-scale region. To quantify clogging, the continuum-scale model implements empirical relations between porosity and continuum-scale parameters, such as permeability and the transverse dispersion coefficient. Solutes are sufficiently mixed at the end of the pore-scale region, such that the initial reaction rate is accurately computed using averaged concentrations in the continuum-scale region. Relative to a fully pore-scale result, we find accuracy of biomass growth in the multiscale model with this decomposition improves as the interface between pore-scale and continuum-scale regions moves downgradient where transverse mixing is more fully developed. Also, this decomposition poses additional challenges with respect to mortar coupling. We explore these challenges and potential solutions. While recent work has demonstrated growing interest in multiscale models, further development is needed for their application to field-scale subsurface contaminant transport and remediation.

Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

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

Skinner, F. K.; Department of Medicine; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8

There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease.more » Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.« less

Physically based modeling in catchment hydrology at 50: Survey and outlook

NASA Astrophysics Data System (ADS)

Paniconi, Claudio; Putti, Mario

2015-09-01

Integrated, process-based numerical models in hydrology are rapidly evolving, spurred by novel theories in mathematical physics, advances in computational methods, insights from laboratory and field experiments, and the need to better understand and predict the potential impacts of population, land use, and climate change on our water resources. At the catchment scale, these simulation models are commonly based on conservation principles for surface and subsurface water flow and solute transport (e.g., the Richards, shallow water, and advection-dispersion equations), and they require robust numerical techniques for their resolution. Traditional (and still open) challenges in developing reliable and efficient models are associated with heterogeneity and variability in parameters and state variables; nonlinearities and scale effects in process dynamics; and complex or poorly known boundary conditions and initial system states. As catchment modeling enters a highly interdisciplinary era, new challenges arise from the need to maintain physical and numerical consistency in the description of multiple processes that interact over a range of scales and across different compartments of an overall system. This paper first gives an historical overview (past 50 years) of some of the key developments in physically based hydrological modeling, emphasizing how the interplay between theory, experiments, and modeling has contributed to advancing the state of the art. The second part of the paper examines some outstanding problems in integrated catchment modeling from the perspective of recent developments in mathematical and computational science.

Modelling the impacts of pests and diseases on agricultural systems.

PubMed

Donatelli, M; Magarey, R D; Bregaglio, S; Willocquet, L; Whish, J P M; Savary, S

2017-07-01

The improvement and application of pest and disease models to analyse and predict yield losses including those due to climate change is still a challenge for the scientific community. Applied modelling of crop diseases and pests has mostly targeted the development of support capabilities to schedule scouting or pesticide applications. There is a need for research to both broaden the scope and evaluate the capabilities of pest and disease models. Key research questions not only involve the assessment of the potential effects of climate change on known pathosystems, but also on new pathogens which could alter the (still incompletely documented) impacts of pests and diseases on agricultural systems. Yield loss data collected in various current environments may no longer represent a adequate reference to develop tactical, decision-oriented, models for plant diseases and pests and their impacts, because of the ongoing changes in climate patterns. Process-based agricultural simulation modelling, on the other hand, appears to represent a viable methodology to estimate the impacts of these potential effects. A new generation of tools based on state-of-the-art knowledge and technologies is needed to allow systems analysis including key processes and their dynamics over appropriate suitable range of environmental variables. This paper offers a brief overview of the current state of development in coupling pest and disease models to crop models, and discusses technical and scientific challenges. We propose a five-stage roadmap to improve the simulation of the impacts caused by plant diseases and pests; i) improve the quality and availability of data for model inputs; ii) improve the quality and availability of data for model evaluation; iii) improve the integration with crop models; iv) improve the processes for model evaluation; and v) develop a community of plant pest and disease modelers.

HSPF Modeling for Compliance and Enforcement: An Urban Case Study

NASA Astrophysics Data System (ADS)

Marshalonis, D.

2017-12-01

Stormwater runoff is one of the most significant challenges to water quality facing surface waters globally. In the United States, the Environmental Protection Agency (EPA) regulates stormwater flows through its National Pollutant Discharge Elimination System (NPDES) program permits. When egregious violations occur, EPA may develop its case and prove those violations through the legal dispute process. However, evidence in stormwater-related cases is ephemeral, difficult to collect due to unpredictable weather dynamics, and there are usually no witnesses. The work presented here illustrates an approach EPA takes for certain wet weather cases: introduce results from hydrologic and hydraulic models as evidence to meet legal burden of proof standards. The challenges and opportunities of using models in stormwater discharge modeling are highlighted.

Recent Developments and Challenges Implementing New and Improved Stress Intensity Factor (K) Solutions in NASGRO for Damage Tolerance Analyses

NASA Technical Reports Server (NTRS)

Cardinal, Joseph W.; McClung, R. Craig; Lee, Yi-Der; Guo, Yajun; Beek, Joachim M.

2014-01-01

Fatigue crack growth analysis software has been available to damage tolerance analysts for many years in either commercial products or via proprietary in-house codes. The NASGRO software has been publicly available since the mid-80s (known as NASA/FLAGRO up to 1999) and since 2000 has been sustained and further developed by a collaborative effort between Southwest Research Institute® (SwRI®), the NASA Johnson Space Center (JSC), and the members of the NASGRO Industrial Consortium. Since the stress intensity factor (K) is the foundation of fracture mechanics and damage tolerance analysis of aircraft structures, a significant focus of development efforts in the past fifteen years has been geared towards enhancing legacy K solutions and developing new and efficient numerical K solutions that can handle the complicated stress gradients computed by today’s analysts using detailed finite element models of fatigue critical locations. This paper provides an overview of K solutions that have been recently implemented or improved for the analysis of geometries such as two unequal through cracks at a hole and two unequal corner cracks at a hole, as well as state-of-the-art weight function models capable of computing K in the presence of univariant and/or bivariant stress gradients and complicated residual stress distributions. Some historical background is provided to review how common K solutions have evolved over the years, including selective examples from the literature and from new research. Challenges and progress in rectifying discrepancies between older legacy solutions and newer models are reviewed as well as approaches and challenges for verification and validation of K solutions. Finally, a summary of current challenges and future research and development needs is presented. A key theme throughout the presentation of this paper will be how members of the aerospace industry have collaborated with software developers to develop a practical analysis tool that is used world-wide to support new design as well as the ongoing sustainment and airworthiness of commercial and military aircraft.

Toward Realism in Human Performance Simulation

DTIC Science & Technology

2004-01-01

toward the development of improved human-like performance of synthetic agents. However, several serious problems continue to challenge researchers and... developers . Developers have insufficient behavioral knowledge. To date, models of emotivity and behavior that have been commercialized still tend...Bindiganavale, 1999). There has even been significant development of architectures to produce animated characters that react appropriately to a small

Information and Communication Technologies: A Tool Empowering and Developing the Horizon of the Learner

ERIC Educational Resources Information Center

Debande, Olivier; Ottersten, Eugenia Kazamaki

2004-01-01

In this article, we focus on the implementation and development of ICT in the education sector, challenging and developing the traditional learning environment whilst introducing new educational tools including e-learning. The paper investigates ICT as a tool empowering and developing learners lifelong learning opportunities. It defines a model of…

Sparse models for correlative and integrative analysis of imaging and genetic data

PubMed Central

Lin, Dongdong; Cao, Hongbao; Calhoun, Vince D.

2014-01-01

The development of advanced medical imaging technologies and high-throughput genomic measurements has enhanced our ability to understand their interplay as well as their relationship with human behavior by integrating these two types of datasets. However, the high dimensionality and heterogeneity of these datasets presents a challenge to conventional statistical methods; there is a high demand for the development of both correlative and integrative analysis approaches. Here, we review our recent work on developing sparse representation based approaches to address this challenge. We show how sparse models are applied to the correlation and integration of imaging and genetic data for biomarker identification. We present examples on how these approaches are used for the detection of risk genes and classification of complex diseases such as schizophrenia. Finally, we discuss future directions on the integration of multiple imaging and genomic datasets including their interactions such as epistasis. PMID:25218561

A Review of Hypothesized Determinants Associated with Bighorn Sheep (Ovis canadensis) Die-Offs

PubMed Central

Miller, David S.; Hoberg, Eric; Weiser, Glen; Aune, Keith; Atkinson, Mark; Kimberling, Cleon

2012-01-01

Multiple determinants have been hypothesized to cause or favor disease outbreaks among free-ranging bighorn sheep (Ovis canadensis) populations. This paper considered direct and indirect causes of mortality, as well as potential interactions among proposed environmental, host, and agent determinants of disease. A clear, invariant relationship between a single agent and field outbreaks has not yet been documented, in part due to methodological limitations and practical challenges associated with developing rigorous study designs. Therefore, although there is a need to develop predictive models for outbreaks and validated mitigation strategies, uncertainty remains as to whether outbreaks are due to endemic or recently introduced agents. Consequently, absence of established and universal explanations for outbreaks contributes to conflict among wildlife and livestock stakeholders over land use and management practices. This example illustrates the challenge of developing comprehensive models for understanding and managing wildlife diseases in complex biological and sociological environments. PMID:22567546

Dynamic Metabolic Model Building Based on the Ensemble Modeling Approach

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

Liao, James C.

2016-10-01

Ensemble modeling of kinetic systems addresses the challenges of kinetic model construction, with respect to parameter value selection, and still allows for the rich insights possible from kinetic models. This project aimed to show that constructing, implementing, and analyzing such models is a useful tool for the metabolic engineering toolkit, and that they can result in actionable insights from models. Key concepts are developed and deliverable publications and results are presented.

OECD-NEA Expert Group on Multi-Physics Experimental Data, Benchmarks and Validation

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

Valentine, Timothy; Rohatgi, Upendra S.

High-fidelity, multi-physics modeling and simulation (M&S) tools are being developed and utilized for a variety of applications in nuclear science and technology and show great promise in their abilities to reproduce observed phenomena for many applications. Even with the increasing fidelity and sophistication of coupled multi-physics M&S tools, the underpinning models and data still need to be validated against experiments that may require a more complex array of validation data because of the great breadth of the time, energy and spatial domains of the physical phenomena that are being simulated. The Expert Group on Multi-Physics Experimental Data, Benchmarks and Validationmore » (MPEBV) of the Nuclear Energy Agency (NEA) of the Organization for Economic Cooperation and Development (OECD) was formed to address the challenges with the validation of such tools. The work of the MPEBV expert group is shared among three task forces to fulfill its mandate and specific exercises are being developed to demonstrate validation principles for common industrial challenges. This paper describes the overall mission of the group, the specific objectives of the task forces, the linkages among the task forces, and the development of a validation exercise that focuses on a specific reactor challenge problem.« less

A high‐resolution global flood hazard model†

PubMed Central

Smith, Andrew M.; Bates, Paul D.; Neal, Jeffrey C.; Alfieri, Lorenzo; Freer, Jim E.

2015-01-01

Abstract Floods are a natural hazard that affect communities worldwide, but to date the vast majority of flood hazard research and mapping has been undertaken by wealthy developed nations. As populations and economies have grown across the developing world, so too has demand from governments, businesses, and NGOs for modeled flood hazard data in these data‐scarce regions. We identify six key challenges faced when developing a flood hazard model that can be applied globally and present a framework methodology that leverages recent cross‐disciplinary advances to tackle each challenge. The model produces return period flood hazard maps at ∼90 m resolution for the whole terrestrial land surface between 56°S and 60°N, and results are validated against high‐resolution government flood hazard data sets from the UK and Canada. The global model is shown to capture between two thirds and three quarters of the area determined to be at risk in the benchmark data without generating excessive false positive predictions. When aggregated to ∼1 km, mean absolute error in flooded fraction falls to ∼5%. The full complexity global model contains an automatically parameterized subgrid channel network, and comparison to both a simplified 2‐D only variant and an independently developed pan‐European model shows the explicit inclusion of channels to be a critical contributor to improved model performance. While careful processing of existing global terrain data sets enables reasonable model performance in urban areas, adoption of forthcoming next‐generation global terrain data sets will offer the best prospect for a step‐change improvement in model performance. PMID:27594719

Opportunities and challenges in developing deep learning models using electronic health records data: a systematic review.

PubMed

Xiao, Cao; Choi, Edward; Sun, Jimeng

2018-06-08

To conduct a systematic review of deep learning models for electronic health record (EHR) data, and illustrate various deep learning architectures for analyzing different data sources and their target applications. We also highlight ongoing research and identify open challenges in building deep learning models of EHRs. We searched PubMed and Google Scholar for papers on deep learning studies using EHR data published between January 1, 2010, and January 31, 2018. We summarize them according to these axes: types of analytics tasks, types of deep learning model architectures, special challenges arising from health data and tasks and their potential solutions, as well as evaluation strategies. We surveyed and analyzed multiple aspects of the 98 articles we found and identified the following analytics tasks: disease detection/classification, sequential prediction of clinical events, concept embedding, data augmentation, and EHR data privacy. We then studied how deep architectures were applied to these tasks. We also discussed some special challenges arising from modeling EHR data and reviewed a few popular approaches. Finally, we summarized how performance evaluations were conducted for each task. Despite the early success in using deep learning for health analytics applications, there still exist a number of issues to be addressed. We discuss them in detail including data and label availability, the interpretability and transparency of the model, and ease of deployment.

Methodological challenges and analytic opportunities for modeling and interpreting Big Healthcare Data.

PubMed

Dinov, Ivo D

2016-01-01

Managing, processing and understanding big healthcare data is challenging, costly and demanding. Without a robust fundamental theory for representation, analysis and inference, a roadmap for uniform handling and analyzing of such complex data remains elusive. In this article, we outline various big data challenges, opportunities, modeling methods and software techniques for blending complex healthcare data, advanced analytic tools, and distributed scientific computing. Using imaging, genetic and healthcare data we provide examples of processing heterogeneous datasets using distributed cloud services, automated and semi-automated classification techniques, and open-science protocols. Despite substantial advances, new innovative technologies need to be developed that enhance, scale and optimize the management and processing of large, complex and heterogeneous data. Stakeholder investments in data acquisition, research and development, computational infrastructure and education will be critical to realize the huge potential of big data, to reap the expected information benefits and to build lasting knowledge assets. Multi-faceted proprietary, open-source, and community developments will be essential to enable broad, reliable, sustainable and efficient data-driven discovery and analytics. Big data will affect every sector of the economy and their hallmark will be 'team science'.

Case Report: Successful Sporozoite Challenge Model in Human Volunteers with Plasmodium vivax Strain Derived from Human Donors

PubMed Central

Herrera, Sócrates; Fernández, Olga; Manzano, María R.; Murrain, Bermans; Vergara, Juana; Blanco, Pedro; Palacios, Ricardo; Vélez, Juan D.; Epstein, Judith E.; Chen-Mok, Mario; Reed, Zarifah H.; Arévalo-Herrera, Myriam

2010-01-01

Successful establishment of a Plasmodium vivax sporozoite challenge model in humans is described. Eighteen healthy adult, malaria-naïve volunteers were randomly allocated to Groups A–C and exposed to 3 ± 1, 6 ± 1, and 9 ± 1 bites of Anopheles albimanus mosquitoes infected with P. vivax, respectively. Seventeen volunteers developed signs and symptoms consistent with malaria, and geometric mean prepatent periods of 11.1 days (9.3–11) for Group A; 10.8 days (9.8–11.9) for Group B; and 10.6 days (8.7–12.4) for Group C, with no statistically significant difference among groups (Kruskal-Wallis, P = 0.70). One volunteer exposed to eight mosquito bites did not develop a parasitemia. No differences in parasite density were observed and all individuals successfully recovered after anti-malarial treatment. None of the volunteers developed parasite relapses within an 18-month follow-up. In conclusion, malaria-naive volunteers can be safely and reproducibly infected with bites of 2–10 An. albimanus mosquitoes carrying P. vivax sporozoites. This challenge method is suitable for vaccine and anti-malarial drug testing. PMID:19861603

An Overview of Numerical Weather Prediction on Various Scales

NASA Astrophysics Data System (ADS)

Bao, J.-W.

2009-04-01

The increasing public need for detailed weather forecasts, along with the advances in computer technology, has motivated many research institutes and national weather forecasting centers to develop and run global as well as regional numerical weather prediction (NWP) models at high resolutions (i.e., with horizontal resolutions of ~10 km or higher for global models and 1 km or higher for regional models, and with ~60 vertical levels or higher). The need for running NWP models at high horizontal and vertical resolutions requires the implementation of non-hydrostatic dynamic core with a choice of horizontal grid configurations and vertical coordinates that are appropriate for high resolutions. Development of advanced numerics will also be needed for high resolution global and regional models, in particular, when the models are applied to transport problems and air quality applications. In addition to the challenges in numerics, the NWP community is also facing the challenges of developing physics parameterizations that are well suited for high-resolution NWP models. For example, when NWP models are run at resolutions of ~5 km or higher, the use of much more detailed microphysics parameterizations than those currently used in NWP model will become important. Another example is that regional NWP models at ~1 km or higher only partially resolve convective energy containing eddies in the lower troposphere. Parameterizations to account for the subgrid diffusion associated with unresolved turbulence still need to be developed. Further, physically sound parameterizations for air-sea interaction will be a critical component for tropical NWP models, particularly for hurricane predictions models. In this review presentation, the above issues will be elaborated on and the approaches to address them will be discussed.

Mi-STAR Unit Challenges serve as a model for integrating earth science and systems thinking in a Next Generation Science Standards (NGSS) aligned curriculum.

NASA Astrophysics Data System (ADS)

Gochis, E. E.; Tubman, S.; Matthys, T.; Bluth, G.; Oppliger, D.; Danhoff, B.; Huntoon, J. E.

2017-12-01

Michigan Science Teaching and Assessment Reform (Mi-STAR) is developing an NGSS-aligned middle school curriculum and associated teacher professional learning program in which science is taught and learned as an integrated body of knowledge that can be applied to address societal issues. With the generous support of the Herbert H. and Grace A. Dow Foundation, Mi-STAR has released several pilot-tested units through the Mi-STAR curriculum portal at mi-star.mtu.edu. Each of these units focuses on an ongoing `Unit Challenge' investigation that integrates STEM content across disciplinary boundaries, stimulates interest, and engages students in using scientific practices to address 21st century challenges. Each Mi-STAR unit is connected to a Unifying NGSS Crosscutting Concept (CCC) that allows students to recognize the concepts that are related to the phenomena or problems under investigation. In the 6th grade, students begin with an exploration of the CCC Systems and System Models. Through repeated applications across units, students refine their understanding of what a system is and how to model a complex Earth system. An example 6th grade unit entitled "Water on the Move: The Water Cycle," provides an example of how Mi-STAR approaches the use of Unifying CCCs and Unit Challenges to enhance middle school students' understanding of the interconnections of Earth system processes and human activities. Throughout the unit, students use a series of hands-on explorations and simulations to explore the hydrologic cycle and how human activity can alter Earth systems. Students develop new knowledge through repeated interactions with the Unit Challenge, which requires development of system models and construction of evidence-based arguments related to flooding problems in a local community. Students have the opportunity to make predictions about how proposed land-use management practices (e.g. development of a skate-park, rain garden, soccer field, etc.) can alter the earth-system processes. Students present their findings and recommendations in a public forum format. Student-learning outcomes are measured using a combination of formative and summative assessments that address students' proficiency with science and engineering content and practices in conjunction with the unit's Unifying CCC.

Item Response Models for Examinee-Selected Items

ERIC Educational Resources Information Center

Wang, Wen-Chung; Jin, Kuan-Yu; Qiu, Xue-Lan; Wang, Lei

2012-01-01

In some tests, examinees are required to choose a fixed number of items from a set of given items to answer. This practice creates a challenge to standard item response models, because more capable examinees may have an advantage by making wiser choices. In this study, we developed a new class of item response models to account for the choice…

Prevent-Teach-Reinforce: The School-Based Model of Individualized Positive Behavior Support

ERIC Educational Resources Information Center

Dunlap, Glen; Iovannone, Rose; Kincaid, Donald; Wilson, Kelly; Christiansen, Kathy; Strain, Phillip; English, Carie

2010-01-01

Solve serious behavior challenges in K-8 classrooms with this easy-to-use book, the first practical guide to the research-proven Prevent-Teach-Reinforce (PTR) model. Developed by some of the most respected authorities on positive behavior support, this innovative model gives school-based teams a five-step plan for reducing problems unresolved by…

Models for Effective Service Delivery in Special Education Programs

ERIC Educational Resources Information Center

Epler, Pam; Ross, Rorie

2015-01-01

Educators today are challenged with the task of designing curricula and standards for students of varying abilities. While technology and innovation steadily improve classroom learning, teachers and administrators continue to struggle in developing the best methodologies and practices for students with disabilities. "Models for Effective…

Approaches to Classroom-Based Computational Science.

ERIC Educational Resources Information Center

Guzdial, Mark

Computational science includes the use of computer-based modeling and simulation to define and test theories about scientific phenomena. The challenge for educators is to develop techniques for implementing computational science in the classroom. This paper reviews some previous work on the use of simulation alone (without modeling), modeling…

Leading Generative Groups: A Conceptual Model

ERIC Educational Resources Information Center

London, Manuel; Sobel-Lojeski, Karen A.; Reilly, Richard R.

2012-01-01

This article presents a conceptual model of leadership in generative groups. Generative groups have diverse team members who are expected to develop innovative solutions to complex, unstructured problems. The challenge for leaders of generative groups is to balance (a) establishing shared goals with recognizing members' vested interests, (b)…

Additive Effect of Diesel Exhaust Particulates and Ozone on Airway Hyperresponsiveness and Inflammation in a Mouse Model of Asthma

PubMed Central

Choi, Inseon-S; Takizawa, Hajime; Rhim, TaiYoun; Lee, June-Hyuk; Park, Sung-Woo; Park, Choon-Sik

2005-01-01

Allergic airway diseases are related to exposure to atmospheric pollutants, which have been suggested to be one factor in the increasing prevalence of asthma. Little is known about the effect of ozone and diesel exhaust particulates (DEP) on the development or aggravation of asthma. We have used a mouse asthma model to determine the effect of ozone and DEP on airway hyperresponsiveness and inflammation. Methacholine enhanced pause (Penh) was measured. Levels of IL-4 and IFN-γ were quantified in bronchoalveolar lavage fluids by enzyme immunoassays. The OVA-sensitized-challenged and ozone and DEP exposure group had higher Penh than the OVA-sensitized-challenged group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone exposure group. Levels of IFN-γ were decreased in the OVA-sensitized-challenged and DEP exposure group and the OVA-sensitized-challenged and ozone and DEP exposure group compared to the OVA-sensitized-challenged and ozone exposure group. Levels of IL-4 were increased in the OVA-sensitized-challenged and ozone exposure group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone and DEP exposure group compared to OVA-sensitized-challenged group. Co-exposure of ozone and DEP has additive effect on airway hyperresponsiveness by modulation of IL-4 and IFN-γ suggesting that DEP amplify Th2 immune response. PMID:16224148

The Center for Coastal Studies: Sustainable Development Education in Mexico

ERIC Educational Resources Information Center

Ollervides, F.; Farrell, T.

2007-01-01

Purpose: The purpose of this paper is to present The School for Field Studies-Center for Coastal Studies (SFS-CCS) as a success story in sustainable development education. This success is based on a unique academic model, which incorporates sustainable development opportunities and challenges faced by the local community into the program…

Managing Reward in Developing Economies: The Challenge for Multinational Corporations

ERIC Educational Resources Information Center

Opute, John

2010-01-01

Reward has been, and continues to be, subject to significant changes in developing economies; the industrial relations model prevalent being driven by the complex socio-economic and cultural paradigms and the increasing demands of globalisation. The issue of reward in developing economies is therefore central and dependent on numerous contextual…

Development and Modification of a Response Class via Positive and Negative Reinforcement: A Translational Approach

ERIC Educational Resources Information Center

Mendres, Amber E.; Borrero, John C.

2010-01-01

When responses function to produce the same reinforcer, a response class exists. Researchers have examined response classes in applied settings; however, the challenges associated with conducting applied research on response class development have recently necessitated the development of an analogue response class model. To date, little research…

Challenges of developing a cardiovascular risk calculator for patients with rheumatoid arthritis.

PubMed

Crowson, Cynthia S; Rollefstad, Silvia; Kitas, George D; van Riel, Piet L C M; Gabriel, Sherine E; Semb, Anne Grete

2017-01-01

Cardiovascular disease (CVD) risk calculators designed for use in the general population do not accurately predict the risk of CVD among patients with rheumatoid arthritis (RA), who are at increased risk of CVD. The process of developing risk prediction models involves numerous issues. Our goal was to develop a CVD risk calculator for patients with RA. Thirteen cohorts of patients with RA originating from 10 different countries (UK, Norway, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico) were combined. CVD risk factors and RA characteristics at baseline, in addition to information on CVD outcomes were collected. Cox models were used to develop a CVD risk calculator, considering traditional CVD risk factors and RA characteristics. Model performance was assessed using measures of discrimination and calibration with 10-fold cross-validation. A total of 5638 RA patients without prior CVD were included (mean age: 55 [SD: 14] years, 76% female). During a mean follow-up of 5.8 years (30139 person years), 389 patients developed a CVD event. Event rates varied between cohorts, necessitating inclusion of high and low risk strata in the models. The multivariable analyses revealed 2 risk prediction models including either a disease activity score including a 28 joint count and erythrocyte sedimentation rate (DAS28ESR) or a health assessment questionnaire (HAQ) along with age, sex, presence of hypertension, current smoking and ratio of total cholesterol to high-density lipoprotein cholesterol. Unfortunately, performance of these models was similar to general population CVD risk calculators. Efforts to develop a specific CVD risk calculator for patients with RA yielded 2 potential models including RA disease characteristics, but neither demonstrated improved performance compared to risk calculators designed for use in the general population. Challenges encountered and lessons learned are discussed in detail.

Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

PubMed

Wilczynski, Bartek; Furlong, Eileen E M

2010-04-15

Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Using the NIATx Model to Implement User-Centered Design of Technology for Older Adults.

PubMed

Gustafson, David H; Maus, Adam; Judkins, Julianne; Dinauer, Susan; Isham, Andrew; Johnson, Roberta; Landucci, Gina; Atwood, Amy K

2016-01-14

What models can effectively guide the creation of eHealth and mHealth technologies? This paper describes the use of the NIATx model as a framework for the user-centered design of a new technology for older adults. The NIATx model is a simple framework of process improvement based on the following principles derived from an analysis of decades of research from various industries about why some projects fail and others succeed: (1) Understand and involve the customer; (2) fix key problems; (3) pick an influential change leader; (4) get ideas from outside the field; (5) use rapid-cycle testing. This paper describes the use of these principles in technology development, the strengths and challenges of using this approach in this context, and lessons learned from the process. Overall, the NIATx model enabled us to produce a user-focused technology that the anecdotal evidence available so far suggests is engaging and useful to older adults. The first and fourth principles were especially important in developing the technology; the fourth proved the most challenging to use.

Using the NIATx Model to Implement User-Centered Design of Technology for Older Adults

PubMed Central

Maus, Adam; Judkins, Julianne; Dinauer, Susan; Isham, Andrew; Johnson, Roberta; Landucci, Gina; Atwood, Amy K

2016-01-01

What models can effectively guide the creation of eHealth and mHealth technologies? This paper describes the use of the NIATx model as a framework for the user-centered design of a new technology for older adults. The NIATx model is a simple framework of process improvement based on the following principles derived from an analysis of decades of research from various industries about why some projects fail and others succeed: (1) Understand and involve the customer; (2) fix key problems; (3) pick an influential change leader; (4) get ideas from outside the field; (5) use rapid-cycle testing. This paper describes the use of these principles in technology development, the strengths and challenges of using this approach in this context, and lessons learned from the process. Overall, the NIATx model enabled us to produce a user-focused technology that the anecdotal evidence available so far suggests is engaging and useful to older adults. The first and fourth principles were especially important in developing the technology; the fourth proved the most challenging to use. PMID:27025985

Computational neuroanatomy: ontology-based representation of neural components and connectivity.

PubMed

Rubin, Daniel L; Talos, Ion-Florin; Halle, Michael; Musen, Mark A; Kikinis, Ron

2009-02-05

A critical challenge in neuroscience is organizing, managing, and accessing the explosion in neuroscientific knowledge, particularly anatomic knowledge. We believe that explicit knowledge-based approaches to make neuroscientific knowledge computationally accessible will be helpful in tackling this challenge and will enable a variety of applications exploiting this knowledge, such as surgical planning. We developed ontology-based models of neuroanatomy to enable symbolic lookup, logical inference and mathematical modeling of neural systems. We built a prototype model of the motor system that integrates descriptive anatomic and qualitative functional neuroanatomical knowledge. In addition to modeling normal neuroanatomy, our approach provides an explicit representation of abnormal neural connectivity in disease states, such as common movement disorders. The ontology-based representation encodes both structural and functional aspects of neuroanatomy. The ontology-based models can be evaluated computationally, enabling development of automated computer reasoning applications. Neuroanatomical knowledge can be represented in machine-accessible format using ontologies. Computational neuroanatomical approaches such as described in this work could become a key tool in translational informatics, leading to decision support applications that inform and guide surgical planning and personalized care for neurological disease in the future.

Mechanism for excitation-dependent photoluminescence from graphene quantum dots and other graphene oxide derivates: consensus, debates and challenges

NASA Astrophysics Data System (ADS)

Gan, Zhixing; Xu, Hao; Hao, Yanling

2016-04-01

Luminescent nanomaterials, with wide applications in biosensing, bioimaging, illumination and display techniques, have been consistently garnering enormous research attention. In particular, those with wavelength-controllable emissions could be highly beneficial. Carbon nanostructures, including graphene quantum dots (GQDs) and other graphene oxide derivates (GODs), with excitation-dependent photoluminescence (PL), which means their fluorescence color could be tuned simply by changing the excitation wavelength, have attracted lots of interest. However the intrinsic mechanism for the excitation-dependent PL is still obscure and fiercely debated presently. In this review, we attempt to summarize the latest efforts to explore the mechanism, including the quantum confinement effect, surface traps model, giant red-edge effect, edge states model and electronegativity of heteroatom model, as well as the newly developed synergistic model, to seek some clues to unravel the mechanism. Meanwhile the controversial difficulties for each model are further discussed. Besides this, the challenges and potential influences of the synthetic methodology and development of the materials are illustrated extensively to elicit more thought and constructive attempts toward their application.

Accelerating the Integration of Distributed Water Solutions: A Conceptual Financing Model from the Electricity Sector

NASA Astrophysics Data System (ADS)

Quesnel, Kimberly J.; Ajami, Newsha K.; Wyss, Noemi

2017-11-01

Modern challenges require new approaches to urban water management. One solution in the portfolio of potential strategies is the integration of distributed water infrastructure, practices, and technologies into existing systems. However, many practical barriers have prevented the widespread adoption of these systems in the US. The objective of this paper is to address these challenges by developing a conceptual model encompassing regulatory, financial, and governance components that can be used to incorporate new distributed water solutions into our current network. To construct the model, case studies of successfully implemented distributed electricity systems, specifically energy efficiency and renewable energy technologies, were examined to determine how these solutions have become prominent in recent years and what lessons can be applied to the water sector in a similar pursuit. The proposed model includes four action-oriented elements: catalyzing change, establishing funding sources, using resource pathways, and creating innovative governance structures. As illustrated in the model, the water sector should use suite of coordinated policies to promote change, engage end users through fiscal incentives, and encourage research, development and dissemination of new technologies over time.

Simulation Modeling for Off-Nominal Conditions - Where Are We Today?

NASA Technical Reports Server (NTRS)

Shah, Gautam H.; Foster, John V.; Cunningham, Kevin

2010-01-01

The modeling of aircraft flight characteris4cs in off-nominal or otherwise adverse conditions has become increasingly important for simulation in the loss-of-control arena. Adverse conditions include environmentally-induced upsets such as wind shear or wake vortex encounters; off-nominal flight conditions, such as stall or departure; on-board systems failures; and structural failures or aircraft damage. Spirited discussions in the research community are taking place as to the fidelity and data requirements for adequate representation of vehicle dynamics under such conditions for a host of research areas, including recovery training, flight controls development, trajectory guidance/planning, and envelope limiting. The increasing need for multiple sources of data (empirical, computational, experimental) for modeling across a larger flight envelope leads to challenges in developing methods of appropriately applying or combining such data, particularly in a dynamic flight environment with a physically and/or aerodynamically asymmetric vehicle. Traditional simplifications and symmetry assumptions in current modeling methodology may no longer be valid. Furthermore, once modeled, challenges abound in the validation of flight dynamics characteristics in adverse flight regimes

Collaborative Project: Development of an Isotope-Enabled CESM for Testing Abrupt Climate Changes

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

Liu, Zhengyu

One of the most important validations for a state-of-art Earth System Model (ESM) with respect to climate changes is the simulation of the climate evolution and abrupt climate change events in the Earth’s history of the last 21,000 years. However, one great challenge for model validation is that ESMs usually do not directly simulate geochemical variables that can be compared directly with past proxy records. In this proposal, we have met this challenge by developing the simulation capability of major isotopes in a state-of-art ESM, the Community Earth System Model (CESM), enabling us to make direct model-data comparison by comparingmore » the model directly against proxy climate records. Our isotope-enabled ESM incorporates the capability of simulating key isotopes and geotracers, notably δ 18O, δD, δ 14C, and δ 13C, Nd and Pa/Th. The isotope-enabled ESM have been used to perform some simulations for the last 21000 years. The direct comparison of these simulations with proxy records has shed light on the mechanisms of important climate change events.« less

Accelerating the Integration of Distributed Water Solutions: A Conceptual Financing Model from the Electricity Sector.

PubMed

Quesnel, Kimberly J; Ajami, Newsha K; Wyss, Noemi

2017-11-01

Modern challenges require new approaches to urban water management. One solution in the portfolio of potential strategies is the integration of distributed water infrastructure, practices, and technologies into existing systems. However, many practical barriers have prevented the widespread adoption of these systems in the US. The objective of this paper is to address these challenges by developing a conceptual model encompassing regulatory, financial, and governance components that can be used to incorporate new distributed water solutions into our current network. To construct the model, case studies of successfully implemented distributed electricity systems, specifically energy efficiency and renewable energy technologies, were examined to determine how these solutions have become prominent in recent years and what lessons can be applied to the water sector in a similar pursuit. The proposed model includes four action-oriented elements: catalyzing change, establishing funding sources, using resource pathways, and creating innovative governance structures. As illustrated in the model, the water sector should use suite of coordinated policies to promote change, engage end users through fiscal incentives, and encourage research, development and dissemination of new technologies over time.

Test Driven Development of a Parameterized Ice Sheet Component

NASA Astrophysics Data System (ADS)

Clune, T.

2011-12-01

Test driven development (TDD) is a software development methodology that offers many advantages over traditional approaches including reduced development and maintenance costs, improved reliability, and superior design quality. Although TDD is widely accepted in many software communities, the suitability to scientific software is largely undemonstrated and warrants a degree of skepticism. Indeed, numerical algorithms pose several challenges to unit testing in general, and TDD in particular. Among these challenges are the need to have simple, non-redundant closed-form expressions to compare against the results obtained from the implementation as well as realistic error estimates. The necessity for serial and parallel performance raises additional concerns for many scientific applicaitons. In previous work I demonstrated that TDD performed well for the development of a relatively simple numerical model that simulates the growth of snowflakes, but the results were anecdotal and of limited relevance to far more complex software components typical of climate models. This investigation has now been extended by successfully applying TDD to the implementation of a substantial portion of a new parameterized ice sheet component within a full climate model. After a brief introduction to TDD, I will present techniques that address some of the obstacles encountered with numerical algorithms. I will conclude with some quantitative and qualitative comparisons against climate components developed in a more traditional manner.

Modeling Psychobiological Development in the Post-Genomic Era

ERIC Educational Resources Information Center

Lickliter, Robert

2013-01-01

Psychobiological systems theory is a relational approach to development that challenges the longstanding views that (1) genetic and environmental influences on the phenotype can be meaningfully partitioned and that (2) genes are capable of directly specifying phenotypes. Gilbert Gottlieb's theoretical innovations including the notion of…

In silico Testing of Environmental Impact on Embryonic Vascular Development

EPA Science Inventory

Understanding risks to embryonic development from exposure to environmental chemicals is a significant challenge given the diverse chemical landscape and paucity of data for most of these compounds. EPA’s Virtual Embryo project is building in silico models of morphogenesis to tes...

Guiding the development of family medicine training in Africa through collaboration with the Medical Education Partnership Initiative.

PubMed

Mash, Robert J; de Villiers, Marietjie R; Moodley, Kalay; Nachega, Jean B

2014-08-01

Africa's health care challenges include a high burden of disease, low life expectancy, health workforce shortages, and varying degrees of commitment to primary health care on the part of policy makers and government officials. One overarching goal of the Medical Education Partnership Initiative (MEPI) is to develop models of medical education in Sub-Saharan Africa. To do this, MEPI has created a network of universities and other institutions that, among other things, recognizes the importance of supporting training programs in family medicine. This article provides a framework for assessing the stage of the development of family medicine training in Africa, including the challenges that were encountered and how educational organizations can help to address them. A modified "stages of change" model (precontemplation, contemplation, action, maintenance, and relapse) was used as a conceptual framework to understand the various phases that countries go through in developing family medicine in the public sector and to determine the type of assistance that is useful at each phase.

Hybrid modeling for quality by design and PAT-benefits and challenges of applications in biopharmaceutical industry.

PubMed

von Stosch, Moritz; Davy, Steven; Francois, Kjell; Galvanauskas, Vytautas; Hamelink, Jan-Martijn; Luebbert, Andreas; Mayer, Martin; Oliveira, Rui; O'Kennedy, Ronan; Rice, Paul; Glassey, Jarka

2014-06-01

This report highlights the drivers, challenges, and enablers of the hybrid modeling applications in biopharmaceutical industry. It is a summary of an expert panel discussion of European academics and industrialists with relevant scientific and engineering backgrounds. Hybrid modeling is viewed in its broader sense, namely as the integration of different knowledge sources in form of parametric and nonparametric models into a hybrid semi-parametric model, for instance the integration of fundamental and data-driven models. A brief description of the current state-of-the-art and industrial uptake of the methodology is provided. The report concludes with a number of recommendations to facilitate further developments and a wider industrial application of this modeling approach. These recommendations are limited to further exploiting the benefits of this methodology within process analytical technology (PAT) applications in biopharmaceutical industry. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Open Innovation at NASA: A New Business Model for Advancing Human Health and Performance Innovations

NASA Technical Reports Server (NTRS)

Davis, Jeffrey R.; Richard, Elizabeth E.; Keeton, Kathryn E.

2014-01-01

This paper describes a new business model for advancing NASA human health and performance innovations and demonstrates how open innovation shaped its development. A 45 percent research and technology development budget reduction drove formulation of a strategic plan grounded in collaboration. We describe the strategy execution, including adoption and results of open innovation initiatives, the challenges of cultural change, and the development of virtual centers and a knowledge management tool to educate and engage the workforce and promote cultural change.

Scoring functions for protein-protein interactions.

PubMed

Moal, Iain H; Moretti, Rocco; Baker, David; Fernández-Recio, Juan

2013-12-01

The computational evaluation of protein-protein interactions will play an important role in organising the wealth of data being generated by high-throughput initiatives. Here we discuss future applications, report recent developments and identify areas requiring further investigation. Many functions have been developed to quantify the structural and energetic properties of interacting proteins, finding use in interrelated challenges revolving around the relationship between sequence, structure and binding free energy. These include loop modelling, side-chain refinement, docking, multimer assembly, affinity prediction, affinity change upon mutation, hotspots location and interface design. Information derived from models optimised for one of these challenges can be used to benefit the others, and can be unified within the theoretical frameworks of multi-task learning and Pareto-optimal multi-objective learning. Copyright © 2013 Elsevier Ltd. All rights reserved.

Future Supply Chains Enabled by Continuous Processing—Opportunities and Challenges. May 20–21, 2014 Continuous Manufacturing Symposium

PubMed Central

Srai, Jagjit Singh; Badman, Clive; Krumme, Markus; Futran, Mauricio; Johnston, Craig

2015-01-01

This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily “continuous processing”-based supply chain. The current predominantly “large batch” and centralized manufacturing system designed for the “blockbuster” drug has driven a slow-paced, inventory heavy operating model that is increasingly regarded as inflexible and unsustainable. Indeed, new markets and the rapidly evolving technology landscape will drive more product variety, shorter product life-cycles, and smaller drug volumes, which will exacerbate an already unsustainable economic model. Future supply chains will be required to enhance affordability and availability for patients and healthcare providers alike despite the increased product complexity. In this more challenging supply scenario, we examine the potential for a more pull driven, near real-time demand-based supply chain, utilizing continuous processing where appropriate as a key element of a more “flow-through” operating model. In this discussion paper on future supply chain models underpinned by developments in the continuous manufacture of pharmaceuticals, we have set out; The significant opportunities to moving to a supply chain flow-through operating model, with substantial opportunities in inventory reduction, lead-time to patient, and radically different product assurance/stability regimes. Scenarios for decentralized production models producing a greater variety of products with enhanced volume flexibility. Production, supply, and value chain footprints that are radically different from today's monolithic and centralized batch manufacturing operations. Clinical trial and drug product development cost savings that support more rapid scale-up and market entry models with early involvement of SC designers within New Product Development. The major supply chain and industrial transformational challenges that need to be addressed. The paper recognizes that although current batch operational performance in pharma is far from optimal and not necessarily an appropriate end-state benchmark for batch technology, the adoption of continuous supply chain operating models underpinned by continuous production processing, as full or hybrid solutions in selected product supply chains, can support industry transformations to deliver right-first-time quality at substantially lower inventory profiles. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:840–849, 2015 PMID:25631279

Development and implementation of an integrated chronic disease model in South Africa: lessons in the management of change through improving the quality of clinical practice

PubMed Central

Asmall, Shaidah

2015-01-01

Background South Africa is facing a complex burden of disease arising from a combination of chronic infectious illness and non-communicable diseases. As the burden of chronic diseases (communicable and non-communicable) increases, providing affordable and effective care to the increasing numbers of chronic patients will be an immense challenge. Methods The framework recommended by the Medical Research Council of the United Kingdom for the development and evaluation of complex health interventions was used to conceptualise the intervention. The breakthrough series was utilised for the implementation process. These two frameworks were embedded within the clinical practice improvement model that served as the overarching framework for the development and implementation of the model. Results The Chronic Care Model was ideally suited to improve the facility component and patient experience; however, the deficiencies in other aspects of the health system building blocks necessitated a hybrid model. An integrated chronic disease management model using a health systems approach was initiated across 42 primary health care facilities. The interventions were implemented in a phased approach using learning sessions and action periods to introduce the planned and targeted changes. Conclusion The implementation of the integrated chronic disease management model is feasible at primary care in South Africa provided that systemic challenges and change management are addressed during the implementation process. PMID:26528101

Development and implementation of an integrated chronic disease model in South Africa: lessons in the management of change through improving the quality of clinical practice.

PubMed

Mahomed, Ozayr Haroon; Asmall, Shaidah

2015-01-01

South Africa is facing a complex burden of disease arising from a combination of chronic infectious illness and non-communicable diseases. As the burden of chronic diseases (communicable and non-communicable) increases, providing affordable and effective care to the increasing numbers of chronic patients will be an immense challenge. The framework recommended by the Medical Research Council of the United Kingdom for the development and evaluation of complex health interventions was used to conceptualise the intervention. The breakthrough series was utilised for the implementation process. These two frameworks were embedded within the clinical practice improvement model that served as the overarching framework for the development and implementation of the model. The Chronic Care Model was ideally suited to improve the facility component and patient experience; however, the deficiencies in other aspects of the health system building blocks necessitated a hybrid model. An integrated chronic disease management model using a health systems approach was initiated across 42 primary health care facilities. The interventions were implemented in a phased approach using learning sessions and action periods to introduce the planned and targeted changes. The implementation of the integrated chronic disease management model is feasible at primary care in South Africa provided that systemic challenges and change management are addressed during the implementation process.

Contribution of Submarine Groundwater on the Water-Food Nexus in Coastal Ecosystems: Effects on Biodiversity and Fishery Production

NASA Astrophysics Data System (ADS)

Shoji, J.; Sugimoto, R.; Honda, H.; Tominaga, O.; Taniguchi, M.

2014-12-01

In the past decade, machine-learning methods for empirical rainfall-runoff modeling have seen extensive development. However, the majority of research has focused on a small number of methods, such as artificial neural networks, while not considering other approaches for non-parametric regression that have been developed in recent years. These methods may be able to achieve comparable predictive accuracy to ANN's and more easily provide physical insights into the system of interest through evaluation of covariate influence. Additionally, these methods could provide a straightforward, computationally efficient way of evaluating climate change impacts in basins where data to support physical hydrologic models is limited. In this paper, we use multiple regression and machine-learning approaches to predict monthly streamflow in five highly-seasonal rivers in the highlands of Ethiopia. We find that generalized additive models, random forests, and cubist models achieve better predictive accuracy than ANNs in many basins assessed and are also able to outperform physical models developed for the same region. We discuss some challenges that could hinder the use of such models for climate impact assessment, such as biases resulting from model formulation and prediction under extreme climate conditions, and suggest methods for preventing and addressing these challenges. Finally, we demonstrate how predictor variable influence can be assessed to provide insights into the physical functioning of data-sparse watersheds.

Advanced Model Compounds for Understanding Acid-Catalyzed Lignin Depolymerization: Identification of Renewable Aromatics and a Lignin-Derived Solvent.

PubMed

Lahive, Ciaran W; Deuss, Peter J; Lancefield, Christopher S; Sun, Zhuohua; Cordes, David B; Young, Claire M; Tran, Fanny; Slawin, Alexandra M Z; de Vries, Johannes G; Kamer, Paul C J; Westwood, Nicholas J; Barta, Katalin

2016-07-20

The development of fundamentally new approaches for lignin depolymerization is challenged by the complexity of this aromatic biopolymer. While overly simplified model compounds often lack relevance to the chemistry of lignin, the direct use of lignin streams poses significant analytical challenges to methodology development. Ideally, new methods should be tested on model compounds that are complex enough to mirror the structural diversity in lignin but still of sufficiently low molecular weight to enable facile analysis. In this contribution, we present a new class of advanced (β-O-4)-(β-5) dilinkage models that are highly realistic representations of a lignin fragment. Together with selected β-O-4, β-5, and β-β structures, these compounds provide a detailed understanding of the reactivity of various types of lignin linkages in acid catalysis in conjunction with stabilization of reactive intermediates using ethylene glycol. The use of these new models has allowed for identification of novel reaction pathways and intermediates and led to the characterization of new dimeric products in subsequent lignin depolymerization studies. The excellent correlation between model and lignin experiments highlights the relevance of this new class of model compounds for broader use in catalysis studies. Only by understanding the reactivity of the linkages in lignin at this level of detail can fully optimized lignin depolymerization strategies be developed.

Global inverse modeling of CH4 sources and sinks: an overview of methods

NASA Astrophysics Data System (ADS)

Houweling, Sander; Bergamaschi, Peter; Chevallier, Frederic; Heimann, Martin; Kaminski, Thomas; Krol, Maarten; Michalak, Anna M.; Patra, Prabir

2017-01-01

The aim of this paper is to present an overview of inverse modeling methods that have been developed over the years for estimating the global sources and sinks of CH4. It provides insight into how techniques and estimates have evolved over time and what the remaining shortcomings are. As such, it serves a didactical purpose of introducing apprentices to the field, but it also takes stock of developments so far and reflects on promising new directions. The main focus is on methodological aspects that are particularly relevant for CH4, such as its atmospheric oxidation, the use of methane isotopologues, and specific challenges in atmospheric transport modeling of CH4. The use of satellite retrievals receives special attention as it is an active field of methodological development, with special requirements on the sampling of the model and the treatment of data uncertainty. Regional scale flux estimation and attribution is still a grand challenge, which calls for new methods capable of combining information from multiple data streams of different measured parameters. A process model representation of sources and sinks in atmospheric transport inversion schemes allows the integrated use of such data. These new developments are needed not only to improve our understanding of the main processes driving the observed global trend but also to support international efforts to reduce greenhouse gas emissions.

Which preparatory curriculum for the International Baccalaureate Diploma Programme is best? The challenge for international schools with regard to mathematics and science

NASA Astrophysics Data System (ADS)

Corlu, M. Sencer

2014-12-01

There are two mainstream curricula for international school students at the junior high level: the International Baccalaureate (IB) Middle Years Programme (MYP) and the Cambridge International General Certificate of Secondary Education (IGCSE). The former was developed in the mid-1990s and is currently being relaunched in a 21st-century approach. The latter programme of study was developed by University of Cambridge International Examinations in 1985 and has become popular in recent years among British domestic and international schools worldwide due to the clarity of its learning content. The prevailing uncertainty about which curriculum is best to prepare students for the IB Diploma Programme represents a challenge for international schools. The purpose of the current study is to develop a methodology through causal models which can explain the relationship between student performance in the IGCSE and the Diploma Programme with regard to mathematics and science. The data evaluated here consisted of external examination scores of students who attended a private international high school between the years 2005 and 2012. Two structural equation models were developed. The first model employed a maximum likelihood estimation, while the second model used a Bayesian estimation with a Markov Chain Monte Carlo method. Both models fit the data well. The evidence suggests that the IGCSE provides a good foundational preparation for the Diploma Programme in mathematics and science.

Multiaxial and Thermomechanical Fatigue of Materials: A Historical Perspective and Some Future Challenges

NASA Technical Reports Server (NTRS)

Kalluri, Sreeramesh

2013-01-01

Structural materials used in engineering applications routinely subjected to repetitive mechanical loads in multiple directions under non-isothermal conditions. Over past few decades, several multiaxial fatigue life estimation models (stress- and strain-based) developed for isothermal conditions. Historically, numerous fatigue life prediction models also developed for thermomechanical fatigue (TMF) life prediction, predominantly for uniaxial mechanical loading conditions. Realistic structural components encounter multiaxial loads and non-isothermal loading conditions, which increase potential for interaction of damage modes. A need exists for mechanical testing and development verification of life prediction models under such conditions.

Advanced Modeling and Uncertainty Quantification for Flight Dynamics; Interim Results and Challenges

NASA Technical Reports Server (NTRS)

Hyde, David C.; Shweyk, Kamal M.; Brown, Frank; Shah, Gautam

2014-01-01

As part of the NASA Vehicle Systems Safety Technologies (VSST), Assuring Safe and Effective Aircraft Control Under Hazardous Conditions (Technical Challenge #3), an effort is underway within Boeing Research and Technology (BR&T) to address Advanced Modeling and Uncertainty Quantification for Flight Dynamics (VSST1-7). The scope of the effort is to develop and evaluate advanced multidisciplinary flight dynamics modeling techniques, including integrated uncertainties, to facilitate higher fidelity response characterization of current and future aircraft configurations approaching and during loss-of-control conditions. This approach is to incorporate multiple flight dynamics modeling methods for aerodynamics, structures, and propulsion, including experimental, computational, and analytical. Also to be included are techniques for data integration and uncertainty characterization and quantification. This research shall introduce new and updated multidisciplinary modeling and simulation technologies designed to improve the ability to characterize airplane response in off-nominal flight conditions. The research shall also introduce new techniques for uncertainty modeling that will provide a unified database model comprised of multiple sources, as well as an uncertainty bounds database for each data source such that a full vehicle uncertainty analysis is possible even when approaching or beyond Loss of Control boundaries. Methodologies developed as part of this research shall be instrumental in predicting and mitigating loss of control precursors and events directly linked to causal and contributing factors, such as stall, failures, damage, or icing. The tasks will include utilizing the BR&T Water Tunnel to collect static and dynamic data to be compared to the GTM extended WT database, characterizing flight dynamics in off-nominal conditions, developing tools for structural load estimation under dynamic conditions, devising methods for integrating various modeling elements into a real-time simulation capability, generating techniques for uncertainty modeling that draw data from multiple modeling sources, and providing a unified database model that includes nominal plus increments for each flight condition. This paper presents status of testing in the BR&T water tunnel and analysis of the resulting data and efforts to characterize these data using alternative modeling methods. Program challenges and issues are also presented.

The development and implementation of a decision-making capacity assessment model.

PubMed

Parmar, Jasneet; Brémault-Phillips, Suzette; Charles, Lesley

2015-03-01

Decision-making capacity assessment (DMCA) is an issue of increasing importance for older adults. Current challenges need to be explored, and potential processes and strategies considered in order to address issues of DMCA in a more coordinated manner. An iterative process was used to address issues related to DMCA. This began with recognition of challenges associated with capacity assessments (CAs) by staff at Covenant Health (CH). Review of the literature, as well as discussions with and a survey of staff at three CH sites, resulted in determination of issues related to DMCA. Development of a DMCA Model and demonstration of its feasibility followed. A process was proposed with front-end screening/problem- solving, a well-defined standard assessment, and definition of team member roles. A Capacity Assessment Care Map was formulated based on the process. Documentation was developed consisting of a Capacity Assessment Process Worksheet, Capacity Interview Worksheet, and a brochure. Interactive workshops were delivered to familiarize staff with the DMCA Model. A successful demonstration project led to implementation across all sites in the Capital Health region, and eventual provincial endorsement. Concerns identified in the survey and in the literature regarding CA were addressed through the holistic interdisciplinary approach offered by the DMCA Model.

A Market-Basket Approach to Predict the Acute Aquatic Toxicity of Munitions and Energetic Materials.

PubMed

Burgoon, Lyle D

2016-06-01

An ongoing challenge in chemical production, including the production of insensitive munitions and energetics, is the ability to make predictions about potential environmental hazards early in the process. To address this challenge, a quantitative structure activity relationship model was developed to predict acute fathead minnow toxicity of insensitive munitions and energetic materials. Computational predictive toxicology models like this one may be used to identify and prioritize environmentally safer materials early in their development. The developed model is based on the Apriori market-basket/frequent itemset mining approach to identify probabilistic prediction rules using chemical atom-pairs and the lethality data for 57 compounds from a fathead minnow acute toxicity assay. Lethality data were discretized into four categories based on the Globally Harmonized System of Classification and Labelling of Chemicals. Apriori identified toxicophores for categories two and three. The model classified 32 of the 57 compounds correctly, with a fivefold cross-validation classification rate of 74 %. A structure-based surrogate approach classified the remaining 25 chemicals correctly at 48 %. This result is unsurprising as these 25 chemicals were fairly unique within the larger set.

Challenges to Masculine Transformation Among Urban Low-Income African American Males

PubMed Central

Aronson, Robert E.; Whitehead, Tony L.; Baber, Willie L.

2003-01-01

In this article we describe and analyze the challenges faced by an intervention program that addresses the fatherhood needs of low-income urban African American males. We used life history as the primary research strategy for a qualitative evaluation of a program we refer to as the Healthy Men in Healthy Families Program to better understand the circumstances and trajectory of men’s lives, including how involvement in the program might have benefited them in the pursuit of their fatherhood goals. A model of masculine transformation, developed by Whitehead, was used to interpret changes in manhood/fatherhood attitudes and behaviors that might be associated with the intervention. We combined Whitehead’s model with a social ecology framework to further interpret challenges at intrapersonal, interpersonal, community, and broader societal levels. PMID:12721134

An Integrated Conceptual Framework for the Development of Asian American Children and Youth.

PubMed

Mistry, Jayanthi; Li, Jin; Yoshikawa, Hirokazu; Tseng, Vivian; Tirrell, Jonathan; Kiang, Lisa; Mistry, Rashmita; Wang, Yijie

2016-07-01

The diversity of circumstances and developmental outcomes among Asian American children and youth poses a challenge for scholars interested in Asian American child development. This article addresses the challenge by offering an integrated conceptual framework based on three broad questions: (a) What are theory-predicated specifications of contexts that are pertinent for the development of Asian American children? (b) What are the domains of development and socialization that are particularly relevant? (c) How can culture as meaning-making processes be integrated in conceptualizations of development? The heuristic value of the conceptual model is illustrated by research on Asian American children and youth that examines the interconnected nature of specific features of context, pertinent aspects of development, and interpretive processes. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development

PubMed Central

Meechan, Daniel W.; Maynard, Thomas M.; Fernandez, Alejandra; Karpinski, Beverly A.; Rothblat, Lawrence A.; LaMantia, Anthony S.

2015-01-01

Understanding the developmental etiology of autistic spectrum disorders, attention deficit/hyperactivity disorder and schizophrenia remains a major challenge for establishing new diagnostic and therapeutic approaches to these common, difficult-to-treat diseases that compromise neural circuits in the cerebral cortex. One aspect of this challenge is the breadth and overlap of ASD, ADHD, and SCZ deficits; another is the complexity of mutations associated with each, and a third is the difficulty of analyzing disrupted development in at-risk or affected human fetuses. The identification of distinct genetic syndromes that include behavioral deficits similar to those in ASD, ADHC and SCZ provides a critical starting point for meeting this challenge. We summarize clinical and behavioral impairments in children and adults with one such genetic syndrome, the 22q11.2 Deletion Syndrome, routinely called 22q11DS, caused by micro-deletions of between 1.5 and 3.0 MB on human chromosome 22. Among many syndromic features, including cardiovascular and craniofacial anomalies, 22q11DS patients have a high incidence of brain structural, functional, and behavioral deficits that reflect cerebral cortical dysfunction and fall within the spectrum that defines ASD, ADHD, and SCZ. We show that developmental pathogenesis underlying this apparent genetic “model” syndrome in patients can be defined and analyzed mechanistically using genomically accurate mouse models of the deletion that causes 22q11DS. We conclude that “modeling a model”, in this case 22q11DS as a model for idiopathic ASD, ADHD and SCZ, as well as other behavioral disorders like anxiety frequently seen in 22q11DS patients, in genetically engineered mice provides a foundation for understanding the causes and improving diagnosis and therapy for these disorders of cortical circuit development. PMID:25866365

Basic Training for Skill Development.

ERIC Educational Resources Information Center

B.T.S.D. Review, 1974

1974-01-01

Profound changes in our socioeconomic structure seem to question the relevance of both "institutional" as well as "open school" forms of education. The educator is faced with the challenge of selecting a model, combining models, or devising a new one. Dealing with these fundamental questions, 10 articles have been selected for their potential…

Hierarchical Bayesian Models of Subtask Learning

ERIC Educational Resources Information Center

Anglim, Jeromy; Wynton, Sarah K. A.

2015-01-01

The current study used Bayesian hierarchical methods to challenge and extend previous work on subtask learning consistency. A general model of individual-level subtask learning was proposed focusing on power and exponential functions with constraints to test for inconsistency. To study subtask learning, we developed a novel computer-based booking…

Strategic Enrollment Management (SEM) Decisions and Geographic Information Systems (GIS) for Community Colleges

ERIC Educational Resources Information Center

Baldin, Antoinette M.

2013-01-01

With the changing landscape in enrollment options for potential community college students, community college administrators are looking for ways to forecast enrollment by using strategic enrollment management models. Today, community colleges' administration is challenged to develop, use, and implement enrollment models that support their…

A Culturally Responsive Practice Model for Urban Indian Child Welfare Services.

ERIC Educational Resources Information Center

Mindell, Robert; Vidal de Haymes, Maria; Francisco, Dale

2003-01-01

Describes a collaboration among a university, a state child welfare agency, and a Native American community organization to develop a culturally driven practice model for urban, Native American child welfare. Identifies challenges and opportunities in addressing the needs of urban Native American communities. Concludes with principles for…

DEVELOPMENT AND PEER REVIEW OF TIME-TO-EFFECT MODELS FOR THE ANALYSIS OF NEUROTOXICITY AND OTHER TIME DEPENDENT DATA

EPA Science Inventory

Neurobehavioral studies pose unique challenges for dose-response modeling, including small sample size and relatively large intra-subject variation, repeated measurements over time, multiple endpoints with both continuous and ordinal scales, and time dependence of risk characteri...

Towards a better understanding of the cracking behavior in soils

USDA-ARS?s Scientific Manuscript database

Understanding and modeling shrinkage-induced cracks helps bridge the gap between flow problem in the laboratory and at the field. Modeling flow at the field scale with Darcian fluxes developed at the laboratory scales is challenged with preferential flows attributed to the cracking behavior of soils...

Multi-criteria decision models for forestry and natural resources management: an annotated bibliography

Treesearch

Joseph E. de Steiguer; Leslie Liberti; Albert Schuler; Bruce Hansen

2003-01-01

Foresters and natural resource managers must balance conflicting objectives when developing land-management plans. Conflicts may encompass economic, environmental, social, cultural, technical, and aesthetic objectives. Selecting the best combination of management uses from numerous objectives is difficult and challenging. Multi-Criteria Decision Models (MCDM) provide a...

Toward Dignity in Care: An In-Service Model

ERIC Educational Resources Information Center

Nash, Mary L.; And Others

1977-01-01

How can the dignity or well being of people in the terminal phase of their lives be fostered? A short-term educational program model was developed to assist a group of personnel (N=83) in a hospital for the chronically ill to become more responsive to this challenge. (Author)

Computational modeling of driver speed control with its applications in developing intelligent transportation system to prevent speeding-related accidents.

DOT National Transportation Integrated Search

2013-08-01

Speeding is the leading contributing factor in fatal accidents in NY state, according to NY State Department of Motor : Vehicle Accidents Statistical Summary (2009). Understanding and modeling speeding and speed control is one of major : challenges i...

Turn the Wheel: Integral School Counseling for Male Adolescents.

ERIC Educational Resources Information Center

Forbes, David

2003-01-01

This article formulates an overarching, inclusive model of integral counseling that enables school counselors to help male adolescents challenge the norm of conventional masculinity. The model draws from 3 areas: transpersonal counseling, holistic education, and mindful social action. The aim is to move the students' level of self-development and…

Nurse's Breakout Session Injury/Illness Case Management

NASA Technical Reports Server (NTRS)

Hesselgesser, Connie

2001-01-01

An overview of the work related injury and illness case management model developed at the Johnson Space Center was presented. The major accomplishments and the challenges of implementation were discussed.

Improving PAGER's real-time earthquake casualty and loss estimation toolkit: a challenge

USGS Publications Warehouse

Jaiswal, K.S.; Wald, D.J.

2012-01-01

We describe the on-going developments of PAGER’s loss estimation models, and discuss value-added web content that can be generated related to exposure, damage and loss outputs for a variety of PAGER users. These developments include identifying vulnerable building types in any given area, estimating earthquake-induced damage and loss statistics by building type, and developing visualization aids that help locate areas of concern for improving post-earthquake response efforts. While detailed exposure and damage information is highly useful and desirable, significant improvements are still necessary in order to improve underlying building stock and vulnerability data at a global scale. Existing efforts with the GEM’s GED4GEM and GVC consortia will help achieve some of these objectives. This will benefit PAGER especially in regions where PAGER’s empirical model is less-well constrained; there, the semi-empirical and analytical models will provide robust estimates of damage and losses. Finally, we outline some of the challenges associated with rapid casualty and loss estimation that we experienced while responding to recent large earthquakes worldwide.

Show Me the Evidence: How a Unit Challenge Can Support Middle School Teachers and Students in Investigating Climate Change Using Real-World Data and Science Practices

NASA Astrophysics Data System (ADS)

Gochis, E. E.; Tubman, S.; Grazul, K.; Bluth, G.; Huntoon, J. E.

2017-12-01

Michigan Science Teaching and Assessment Reform (Mi-STAR) is developing an NGSS-aligned integrated science middle school curriculum and associated teacher professional learning program that addresses all performance expectations for the 6-8 grade-band. The Mi-STAR instructional model is a unit- and lesson-level model that scaffolds students in using science practices to investigate scientific phenomena and apply engineering principles to address a real-world challenge. Mi-STAR has developed an 8th grade unit on climate change based on the Mi-STAR instructional model and NGSS performance expectations. The unit was developed in collaboration with Michigan teachers, climate scientists, and curriculum developers. The unit puts students in the role of advisers to local officials who need an evidence-based explanation of climate change and recommendations about community-based actions to address it. Students discover puzzling signs of global climate change, ask questions about these signs, and engage in a series of investigations using simulations and real data to develop scientific models for the mechanisms of climate change. Students use their models as the basis for evidence-based arguments about the causes and impacts of climate change and employ engineering practices to propose local actions in their community to address climate change. Dedicated professional learning supports teachers before and during implementation of the unit. Before implementing the unit, all teachers complete an online self-paced "unit primer" during which they assume the role of their students as they are introduced to the unit challenge. During this experience, teachers experience science as a practice by using real data and simulations to develop a model of the causes of climate change, just as their students will later do. During unit implementation, teachers are part of a professional learning community led by a teacher facilitator in their local area or school. This professional learning community serves as a resource both for implementing student-directed pedagogy and for the development of content knowledge. Eight teachers pilot tested the unit with more than 500 students in spring 2017, and teachers who participated in the first professional learning cohort are currently implementing the unit around Michigan.

Hospital nurses' wellbeing at work: a theoretical model.

PubMed

Utriainen, Kati; Ala-Mursula, Leena; Kyngäs, Helvi

2015-09-01

To develop a theoretical model of hospital nurses' wellbeing at work. The concept of wellbeing at work is presented without an exact definition and without considering different contents. A model was developed in a deductive manner and empirical data collected from nurses (n = 233) working in a university hospital. Explorative factor analysis was used. The main concepts were: patients' experience of high-quality care; assistance and support among nurses; nurses' togetherness and cooperation; fluent practical organisation of work; challenging and meaningful work; freedom to express diverse feelings in the work community; well-conducted everyday nursing; status related to the work itself; fair and supportive leadership; opportunities for professional development; fluent communication with other professionals; and being together with other nurses in an informal way. Themes included: collegial relationships; enhancing high-quality patient care; supportive and fair leadership; challenging, meaningful and well organised work; and opportunities for professional development. Object-dependent wellbeing was supported. Managers should focus on strengthening the positive aspect of wellbeing at work, focusing on providing fluently organised work practices, fair and supportive leadership and togetherness while allowing nurses to implement their own ideas and promote the experience of meaningfulness. © 2014 John Wiley & Sons Ltd.

Efficient development and processing of thermal math models of very large space truss structures

NASA Technical Reports Server (NTRS)

Warren, Andrew H.; Arelt, Joseph E.; Lalicata, Anthony L.

1993-01-01

As the spacecraft moves along the orbit, the truss members are subjected to direct and reflected solar, albedo and planetary infra-red (IR) heating rates, as well as IR heating and shadowing from other spacecraft components. This is a transient process with continuously changing heating loads and the shadowing effects. The resulting nonuniform temperature distribution may cause nonuniform thermal expansion, deflection and stress in the truss elements, truss warping and thermal distortions. There are three challenges in the thermal-structural analysis of the large truss structures. The first is the development of the thermal and structural math models, the second - model processing, and the third - the data transfer between the models. All three tasks require considerable time and computer resources to be done because of a very large number of components involved. To address these challenges a series of techniques of automated thermal math modeling and efficient processing of very large space truss structures were developed. In the process the finite element and finite difference methods are interfaced. A very substantial reduction of the quantity of computations was achieved while assuring a desired accuracy of the results. The techniques are illustrated on the thermal analysis of a segment of the Space Station main truss.

Challenges to achieving sustainable community health development within a donor aid business model.

PubMed

Ashwell, Helen; Barclay, Lesley

2010-06-01

This paper explores the paradox of donor aid being delivered through a business model through a case study in Papua New Guinea. A retrospective review of project implementation and an outcome evaluation provided an opportunity to examine the long-term results and sustainability of a large project. Analysis was informed by data collected from 175 interviews (national, provincial, district and village), 93 community discussions and observations across 10 provinces. Problems with the business model of delivering aid were evident from implementation data and in an evaluation conducted two years after project completion (2006). Compounding the business model effect were challenges of over-ambitious project goals with limited flexibility to adapt to changing circumstances, a donor payment system requiring short-term productivity and excessive reporting requirements. An overly ambitious project design, donor dominance within the business model and limited local counterpart capacity created problems in the community initiatives component of the project. Contractual pressures can negatively influence long-term outcomes that require development of local leadership and capacity. Future planning for donor project designs needs to be flexible, smaller in scope and have a longer timeframe of seven to 10 years. Donor-funded projects need to be sufficiently flexible to apply proven principles of community development, build local ownership and allow adequate time to build counterpart knowledge and skills.

Effects and detection of raw material variability on the performance of near-infrared calibration models for pharmaceutical products.

PubMed

Igne, Benoit; Shi, Zhenqi; Drennen, James K; Anderson, Carl A

2014-02-01

The impact of raw material variability on the prediction ability of a near-infrared calibration model was studied. Calibrations, developed from a quaternary mixture design comprising theophylline anhydrous, lactose monohydrate, microcrystalline cellulose, and soluble starch, were challenged by intentional variation of raw material properties. A design with two theophylline physical forms, three lactose particle sizes, and two starch manufacturers was created to test model robustness. Further challenges to the models were accomplished through environmental conditions. Along with full-spectrum partial least squares (PLS) modeling, variable selection by dynamic backward PLS and genetic algorithms was utilized in an effort to mitigate the effects of raw material variability. In addition to evaluating models based on their prediction statistics, prediction residuals were analyzed by analyses of variance and model diagnostics (Hotelling's T(2) and Q residuals). Full-spectrum models were significantly affected by lactose particle size. Models developed by selecting variables gave lower prediction errors and proved to be a good approach to limit the effect of changing raw material characteristics. Hotelling's T(2) and Q residuals provided valuable information that was not detectable when studying only prediction trends. Diagnostic statistics were demonstrated to be critical in the appropriate interpretation of the prediction of quality parameters. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.

PubMed

Muller, Julius; Parizotto, Eneida; Antrobus, Richard; Francis, James; Bunce, Campbell; Stranks, Amanda; Nichols, Marshall; McClain, Micah; Hill, Adrian V S; Ramasamy, Adaikalavan; Gilbert, Sarah C

2017-06-08

Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR. 1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%). We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.