Fraley, Stephanie I; Hardick, Justin; Masek, Billie J; Jo Masek, Billie; Athamanolap, Pornpat; Rothman, Richard E; Gaydos, Charlotte A; Carroll, Karen C; Wakefield, Teresa; Wang, Tza-Huei; Yang, Samuel
2013-10-01
Comprehensive profiling of nucleic acids in genetically heterogeneous samples is important for clinical and basic research applications. Universal digital high-resolution melt (U-dHRM) is a new approach to broad-based PCR diagnostics and profiling technologies that can overcome issues of poor sensitivity due to contaminating nucleic acids and poor specificity due to primer or probe hybridization inaccuracies for single nucleotide variations. The U-dHRM approach uses broad-based primers or ligated adapter sequences to universally amplify all nucleic acid molecules in a heterogeneous sample, which have been partitioned, as in digital PCR. Extensive assay optimization enables direct sequence identification by algorithm-based matching of melt curve shape and Tm to a database of known sequence-specific melt curves. We show that single-molecule detection and single nucleotide sensitivity is possible. The feasibility and utility of U-dHRM is demonstrated through detection of bacteria associated with polymicrobial blood infection and microRNAs (miRNAs) associated with host response to infection. U-dHRM using broad-based 16S rRNA gene primers demonstrates universal single cell detection of bacterial pathogens, even in the presence of larger amounts of contaminating bacteria; U-dHRM using universally adapted Lethal-7 miRNAs in a heterogeneous mixture showcases the single copy sensitivity and single nucleotide specificity of this approach.
The Future of Computer-Based Toxicity Prediction:
Mechanism-Based Models vs. Information Mining Approaches
When we speak of computer-based toxicity prediction, we are generally referring to a broad array of approaches which rely primarily upon chemical structure ...
Back to the Future: Implementing a Broad Economic, Inquiry-Based Approach to Accounting Education
ERIC Educational Resources Information Center
Frecka, Thomas J.; Morris, Michael H.; Ramanan, Ramachandran
2004-01-01
Motivated by concerns about the quality of accounting education and calls for a broader, more active approach to learning by numerous accounting educators and practitioners over the past 2 decades, the authors of this article sought to provide a framework and example materials to address those issues. The framework makes use of broad, economic…
Broad economic benefits of freight transportation infrastructure improvement.
DOT National Transportation Integrated Search
2012-06-01
This project strives to introduce a novel way to quantify the broad re-organization benefits associated with an : improvement in the freight infrastructure. Using the approach based on 1) the technique known as Field of Influence, and : 2) RAS adjust...
ERIC Educational Resources Information Center
Kupchella, Charles E.
2009-01-01
Higher Education needs to give more broad-based attention to health and wellness. Our graduates will all have to deal with the facts that the general state of health of Americans is not good and our national health care system is badly in need of reform. We should offer innovative approaches to helping our graduates establish positive, lifetime…
Broad-Enrich: functional interpretation of large sets of broad genomic regions.
Cavalcante, Raymond G; Lee, Chee; Welch, Ryan P; Patil, Snehal; Weymouth, Terry; Scott, Laura J; Sartor, Maureen A
2014-09-01
Functional enrichment testing facilitates the interpretation of Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) data in terms of pathways and other biological contexts. Previous methods developed and used to test for key gene sets affected in ChIP-seq experiments treat peaks as points, and are based on the number of peaks associated with a gene or a binary score for each gene. These approaches work well for transcription factors, but histone modifications often occur over broad domains, and across multiple genes. To incorporate the unique properties of broad domains into functional enrichment testing, we developed Broad-Enrich, a method that uses the proportion of each gene's locus covered by a peak. We show that our method has a well-calibrated false-positive rate, performing well with ChIP-seq data having broad domains compared with alternative approaches. We illustrate Broad-Enrich with 55 ENCODE ChIP-seq datasets using different methods to define gene loci. Broad-Enrich can also be applied to other datasets consisting of broad genomic domains such as copy number variations. http://broad-enrich.med.umich.edu for Web version and R package. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press.
Baltimore: A Multifaceted Approach to Developing Relationships
ERIC Educational Resources Information Center
Durham, Rachel E.; Shiller, Jessica; Connolly, Faith
2018-01-01
As community schools spread across the country, community school staff need effective approaches to engaging families and community-based partners. Such principles must be broadly applicable, given community schools' mandate to adapt to different local contexts. Based on recent research on Baltimore City's community schools, the authors highlight…
Kirk D. Sinclair; Barbara A. Knuth
2001-01-01
Private forest landowners support the stewardship objectives that can be achieved through ecosystems-based management. However, ecosystems-based management is a data intensive approach that focuses upon the broad forest landscape. Intervention by forestry agents or agencies could help neighboring landowners to collaborate with an ecosystems-based approach in pursuit of...
Assessing the Humanities in the Primary School Using a Portfolio-Based Approach
ERIC Educational Resources Information Center
Eaude, Tony
2017-01-01
This article suggests that a portfolio-based approach to assessing the humanities in the primary school is appropriate and outlines what this might involve. It argues for a broad interpretation of "the humanities" and for adopting principles associated with formative assessment, where assessment is not equated with testing and a wide…
Filone, Claire Marie; Hodges, Erin N.; Honeyman, Brian; Bushkin, G. Guy; Boyd, Karla; Platt, Andrew; Ni, Feng; Strom, Kyle; Hensley, Lisa; Snyder, John K.; Connor, John H.
2013-01-01
There are no approved therapeutics for the most deadly nonsegmented negative-strand (NNS) RNA viruses, including Ebola (EBOV). To identify new chemical scaffolds for development of broad-spectrum antivirals, we undertook a prototype-based lead identification screen. Using the prototype NNS virus, vesicular stomatitis virus (VSV), multiple inhibitory compounds were identified. Three compounds were investigated for broad-spectrum activity, and inhibited EBOV infection. The most potent, CMLDBU3402, was selected for further study. CMLDBU3402 did not show significant activity against segmented negative-strand RNA viruses suggesting proscribed broad-spectrum activity. Mechanistic analysis indicated that CMLDBU3402 blocked VSV viral RNA synthesis and inhibited EBOV RNA transcription, demonstrating a consistent mechanism of action against genetically distinct viruses. The identification of this chemical backbone as a broad-spectrum inhibitor of viral RNA synthesis offers significant potential for the development of new therapies for highly pathogenic viruses. PMID:23521799
Bullock, Alison; Webb, Katie Louise; Muddiman, Esther; MacDonald, Janet; Allery, Lynne; Pugsley, Lesley
2018-04-12
Changing patient demographics make it ever more challenging to maintain the quality and safety of care. One approach to addressing this is the development of training for generalist doctors who can take a more holistic approach to care. The purpose of the work we report here is to consider whether a broad-based training programme prepares doctors for a changing health service. We adopted a longitudinal, mixed-methods approach, collecting questionnaire data from trainees on the broad-based training (BBT) programme in England (baseline n=62) and comparator trainees in the same regions (baseline n=90). We held 15 focus groups with BBT trainees and one-to-one telephone interviews with trainees post-BBT (n=21) and their Educational Supervisors (n=9). From questionnaire data, compared with comparator groups, BBT trainees were significantly more confident that their training would result in: wider perspectives, understanding specialty complementarity, ability to apply learning across specialties, manage complex patients and provide patient-focused care. Data from interviews and focus groups provided evidence of positive consequences for patient care from BBT trainees' ability to apply knowledge from other specialties. Specifically, insights from BBT enabled trainees to tailor referrals and consider patients' psychological as well as physical needs, thus adopting a more holistic approach to care. Unintended consequences were revealed in focus groups where BBT trainees expressed feelings of isolation. However, when we explored this sentiment on questionnaire surveys, we found that at least as many in the comparator groups sometimes felt isolated. Practitioners with an understanding of care across specialty boundaries can enhance patient care and reduce risks from poor inter-specialty communication. Internationally, there is growing recognition of the place of generalism in medical practice and the need to take a more person-centred approach. Broad-based approaches to training support the development of generalist doctors, which is well-suited to a changing health service. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Dissenting Catholic Theologian Preaches a More Critical Approach to Moral Issues.
ERIC Educational Resources Information Center
Coughlin, Ellen K.
1987-01-01
Charles E. Curran, whose license to teach Catholic theology has been revoked by the Vatican, is part of a broad-based revisionist movement that is challenging the Church's traditional, neoscholastic approach to the discipline. (MSE)
ERIC Educational Resources Information Center
Macias, J. A.
2012-01-01
Project-based learning is one of the main successful student-centered pedagogies broadly used in computing science courses. However, this approach can be insufficient when dealing with practical subjects that implicitly require many deliverables and a great deal of feedback and organizational resources. In this paper, a worked e-portfolio is…
ERIC Educational Resources Information Center
Australian Government Tertiary Education Quality and Standards Agency, 2015
2015-01-01
The Australian Government Tertiary Education Quality and Standards Agency's (TEQSA's) role is to assure that quality standards are being met by all registered higher education providers. This paper explains how TEQSA's risk-based approach to assuring higher education standards is applied in broad terms to a diverse sector. This explanation is…
Jennifer K. Costanza; Don Faber-Langendoen; John W. Coulston; David N. Wear
2018-01-01
Background: Knowledge of the different kinds of tree communities that currently exist can provide a baseline for assessing the ecological attributes of forests and monitoring future changes. Forest inventory data can facilitate the development of this baseline knowledge across broad extents, but they first must be classified into forest...
Evidence-based assessment in pediatric psychology: family measures.
Alderfer, Melissa A; Fiese, Barbara H; Gold, Jeffrey I; Cutuli, J J; Holmbeck, Grayson N; Goldbeck, Lutz; Chambers, Christine T; Abad, Mona; Spetter, Dante; Patterson, Joän
2008-10-01
To provide a review of the evidence base of family measures relevant to pediatric psychology. Twenty-nine family measures were selected based upon endorsement by Division 54 listserv members, expert judgment, and literature review. Spanning observational and self-report methods, the measures fell into three broad assessment categories: Family functioning, Dyadic family relationships, and Family functioning in the context of childhood chronic health conditions. Measures were categorized as: "Well-established", "Approaching well-established", or "Promising." Nineteen measures met "well-established" criteria and the remaining ten were "approaching well-established." "Well-established" measures were documented for each of the broad assessment categories named above. Many measures deemed "well-established" in the general population are proving to be reliable and useful in pediatric samples. More evidence of the validity of family measures is needed in this context. This review should prove helpful to clinicians and researchers as they strive to make evidence-based decisions regarding family measures.
NASA Technical Reports Server (NTRS)
Reagan, John A.; Pilewskie, Peter A.; Scott-Fleming, Ian C.; Herman, Benjamin M.; Ben-David, Avishai
1987-01-01
Techniques for extrapolating earth-based spectral band measurements of directly transmitted solar irradiance to equivalent exoatmospheric signal levels were used to aid in determining system gain settings of the Halogen Occultation Experiment (HALOE) sunsensor being developed for the NASA Upper Atmosphere Research Satellite and for the Stratospheric Aerosol and Gas (SAGE) 2 instrument on the Earth Radiation Budget Satellite. A band transmittance approach was employed for the HALOE sunsensor which has a broad-band channel determined by the spectral responsivity of a silicon detector. A modified Langley plot approach, assuming a square-root law behavior for the water vapor transmittance, was used for the SAGE-2 940 nm water vapor channel.
NASA Technical Reports Server (NTRS)
Reagan, J. A.; Pilewskie, P. A.; Scott-Fleming, I. C.; Hermann, B. M.
1986-01-01
Techniques for extrapolating Earth-based spectral band measurements of directly transmitted solar irradiance to equivalent exoatmospheric signal levels were used to aid in determining system gain settings of the Halogen Occultation Experiment (HALOE) sunsensor system being developed for the NASA Upper Atmosphere Research Satellite and for the Stratospheric Aerosol and Gas (SAGE) 2 instrument on the Earth Radiation Budget Satellite. A band transmittance approach was employed for the HALOE sunsensor which has a broad-band channel determined by the spectral responsivity of a silicon detector. A modified Langley plot approach, assuming a square-root law behavior for the water vapor transmittance, was used for the SAGE-2 940 nm water vapor channel.
ERIC Educational Resources Information Center
Ganesh, Chandrakala; Smith, Jason A.
2017-01-01
Problem-based learning can be an effective educational approach for students entering the health care field. While broadly used in graduate and professional education in the health sciences, it is less widely used in undergraduate programs. We discuss the use of problem-based learning as part of an approach to address failure rates in select…
Network-based recommendation algorithms: A review
NASA Astrophysics Data System (ADS)
Yu, Fei; Zeng, An; Gillard, Sébastien; Medo, Matúš
2016-06-01
Recommender systems are a vital tool that helps us to overcome the information overload problem. They are being used by most e-commerce web sites and attract the interest of a broad scientific community. A recommender system uses data on users' past preferences to choose new items that might be appreciated by a given individual user. While many approaches to recommendation exist, the approach based on a network representation of the input data has gained considerable attention in the past. We review here a broad range of network-based recommendation algorithms and for the first time compare their performance on three distinct real datasets. We present recommendation topics that go beyond the mere question of which algorithm to use-such as the possible influence of recommendation on the evolution of systems that use it-and finally discuss open research directions and challenges.
Reinventing Learning: A Design-Research Odyssey
ERIC Educational Resources Information Center
Abrahamson, Dor
2015-01-01
Design research is a broad, practice-based approach to investigating problems of education. This approach can catalyze the development of learning theory by fostering opportunities for transformational change in scholars' interpretation of instructional interactions. Surveying a succession of design-research projects, I explain how challenges in…
Tolaymat, Thabet; El Badawy, Amro; Sequeira, Reynold; Genaidy, Ash
2015-04-01
There is an urgent need for a trans-disciplinary approach for the collective evaluation of engineered nanomaterial (ENM) benefits and risks. Currently, research studies are mostly focused on examining effects at individual endpoints with emphasis on ENM risk effects. Less research work is pursuing the integration needed to advance the science of sustainable ENMs. Therefore, the primary objective of this article is to discuss the system-of-systems (SoS) approach as a broad and integrated paradigm to examine ENM benefits and risks to society, environment, and economy (SEE) within a sustainability context. The aims are focused on: (a) current approaches in the scientific literature and the need for a broad and integrated approach, (b) documentation of ENM SoS in terms of architecture and governing rules and practices within sustainability context, and (c) implementation plan for the road ahead. In essence, the SoS architecture is a communication vehicle offering the opportunity to track benefits and risks in an integrated fashion so as to understand the implications and make decisions about advancing the science of sustainable ENMs. In support of the SoS architecture, we propose using an analytic-based decision support system consisting of a knowledge base and analytic engine along the benefit and risk informatics routes in the SEE system to build sound decisions on what constitutes sustainable and unsustainable ENMs in spite of the existing uncertainties and knowledge gaps. The work presented herein is neither a systematic review nor a critical appraisal of the scientific literature. Rather, it is a position paper that largely expresses the views of the authors based on their expert opinion drawn from industrial and academic experience. Copyright © 2014. Published by Elsevier B.V.
Discriminantly Valid Personality Measures: Some Propositions. Research Bulletin No. 339.
ERIC Educational Resources Information Center
Jackson, Douglas N.
Starting with the premise that the construct-oriented approach is the only viable approach to personality assessment, this paper considers five propositions. First, a prerequisite to generalizable and valid psychometric measurement of personality rests on the choice of broad-based constructs with systematic univocal definitions. Next, measures…
Measuring Prices in Health Care Markets Using Commercial Claims Data.
Neprash, Hannah T; Wallace, Jacob; Chernew, Michael E; McWilliams, J Michael
2015-12-01
To compare methods of price measurement in health care markets. Truven Health Analytics MarketScan commercial claims. We constructed medical prices indices using three approaches: (1) a "sentinel" service approach based on a single common service in a specific clinical domain, (2) a market basket approach, and (3) a spending decomposition approach. We constructed indices at the Metropolitan Statistical Area level and estimated correlations between and within them. Price indices using a spending decomposition approach were strongly and positively correlated with indices constructed from broad market baskets of common services (r > 0.95). Prices of single common services exhibited weak to moderate correlations with each other and other measures. Market-level price measures that reflect broad sets of services are likely to rank markets similarly. Price indices relying on individual sentinel services may be more appropriate for examining specialty- or service-specific drivers of prices. © Health Research and Educational Trust.
Song, Wei-Li; Zhou, Zhili; Wang, Li-Chen; Cheng, Xiao-Dong; Chen, Mingji; He, Rujie; Chen, Haosen; Yang, Yazheng; Fang, Daining
2017-12-13
Ultra-broad-band electromagnetic absorption materials and structures are increasingly attractive for their critical role in competing with the advanced broad-band electromagnetic detection systems. Mechanically soft and weak wax-based materials composites are known to be insufficient to serve in practical electromagnetic absorption applications. To break through such barriers, here we developed an innovative strategy to enable the wax-based composites to be robust and repairable meta-structures by employing a three-dimensional (3D) printed polymeric patterned shell. Because of the integrated merits from both the dielectric loss wax-based composites and mechanically robust 3D printed shells, the as-fabricated meta-structures enable bear mechanical collision and compression, coupled with ultra-broad-band absorption (7-40 and 75-110 GHz, reflection loss smaller than -10 dB) approaching state-of-the-art electromagnetic absorption materials. With the assistance of experiment and simulation methods, the design advantages and mechanism of employing such 3D printed shells for substantially promoting the electromagnetic absorption performance have been demonstrated. Therefore, such universal strategy that could be widely extended to other categories of wax-based composites highlights a smart stage on which high-performance practical multifunction meta-structures with ultra-broad-band electromagnetic absorption could be envisaged.
Generating Broad-Scale Forest Ownership Maps: A Closest-Neighbor Approach
Brett J. Butler
2005-01-01
A closest-neighbor method for producing a forest ownership map using remotely sensed imagery and point-based ownership information is presented for the Northeastern United States. Based on a validation data set, this method had an accuracy rate of 58 percent.
Wiedner, Susan D.; Burnum, Kristin E.; Pederson, LeeAnna M.; Anderson, Lindsey N.; Fortuin, Suereta; Chauvigné-Hines, Lacie M.; Shukla, Anil K.; Ansong, Charles; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.
2012-01-01
Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli. PMID:22865858
Wiedner, Susan D; Burnum, Kristin E; Pederson, LeeAnna M; Anderson, Lindsey N; Fortuin, Suereta; Chauvigné-Hines, Lacie M; Shukla, Anil K; Ansong, Charles; Panisko, Ellen A; Smith, Richard D; Wright, Aaron T
2012-09-28
Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.
Evidence-based Assessment in Pediatric Psychology: Family Measures
Fiese, Barbara H.; Gold, Jeffrey I.; Cutuli, J. J.; Holmbeck, Grayson N.; Goldbeck, Lutz; Chambers, Christine T.; Abad, Mona; Spetter, Dante; Patterson, Joän
2008-01-01
Objective To provide a review of the evidence base of family measures relevant to pediatric psychology. Method Twenty-nine family measures were selected based upon endorsement by Division 54 listserv members, expert judgment, and literature review. Spanning observational and self-report methods, the measures fell into three broad assessment categories: Family functioning, Dyadic family relationships, and Family functioning in the context of childhood chronic health conditions. Measures were categorized as: “Well-established”, “Approaching well-established”, or “Promising.” Results Nineteen measures met “well-established” criteria and the remaining ten were “approaching well-established.” “Well-established” measures were documented for each of the broad assessment categories named above. Conclusions Many measures deemed “well-established” in the general population are proving to be reliable and useful in pediatric samples. More evidence of the validity of family measures is needed in this context. This review should prove helpful to clinicians and researchers as they strive to make evidence-based decisions regarding family measures. PMID:17905801
Reducing maternal anxiety and stress in pregnancy: what is the best approach?
Fontein-Kuipers, Yvonne
2015-04-01
To briefly review results of the latest research on approaching antenatal maternal anxiety and stress as distinct constructs within a broad spectrum of maternal antenatal distress and the preventive strategic role of the maternal healthcare practitioner. Maternal antenatal anxiety and stress are predominant contributors to short and long-term ill health and reduction of these psychological constructs is evident. Anxiety and stress belong to a broad spectrum of different psychological constructs. Various psychometric instruments are available to measure different individual constructs of antenatal maternal emotional health. Using multiple measures within antenatal care would imply a one-dimensional approach of individual constructs, resulting in inadequate management of care and inefficient use of knowledge and skills of maternity healthcare practitioners. A case-finding approach with slight emphasis on antenatal anxiety with subsequent selection of at-risk women and women suffering from maternal distress are shown to be effective preventive strategies and are consistent with the update of the National Institute for Health and Care Excellence guideline 'Antenatal and postnatal mental health'. Educational aspects of this approach are related to screening and assessment. A shift in perception and attitude towards a broad theoretical and practical approach of antenatal maternal mental health and well-being is required. Case finding with subsequent selective and indicated preventive strategies during pregnancy would conform to this approach and are evidence based.
ERIC Educational Resources Information Center
Reinschmidt, Kerstin M.; Teufel-Shone, Nicolette I.; Bradford, Gail; Drummond, Rebecca L.; Torres, Emma; Redondo, Floribella; Elenes, Jo Jean; Sanders, Alicia; Gastelum, Sylvia; Moore-Monroy, Martha; Barajas, Salvador; Fernandez, Lourdes; Alvidrez, Rosy; de Zapien, Jill Guernsey; Staten, Lisa K.
2010-01-01
Diabetes health disparities among Hispanic populations have been countered with federally funded health promotion and disease prevention programs. Dissemination has focused on program adaptation to local cultural contexts for greater acceptability and sustainability. Taking a broader approach and drawing on our experience in Mexican American…
Phonetics Information Base and Lexicon
ERIC Educational Resources Information Center
Moran, Steven Paul
2012-01-01
In this dissertation, I investigate the linguistic and technological challenges involved in creating a cross-linguistic data set to undertake phonological typology. I then address the question of whether more sophisticated, knowledge-based approaches to data modeling, coupled with a broad cross-linguistic data set, can extend previous typological…
Weber, Marc; Teeling, Hanno; Huang, Sixing; Waldmann, Jost; Kassabgy, Mariette; Fuchs, Bernhard M; Klindworth, Anna; Klockow, Christine; Wichels, Antje; Gerdts, Gunnar; Amann, Rudolf; Glöckner, Frank Oliver
2011-05-01
Next-generation sequencing (NGS) technologies have enabled the application of broad-scale sequencing in microbial biodiversity and metagenome studies. Biodiversity is usually targeted by classifying 16S ribosomal RNA genes, while metagenomic approaches target metabolic genes. However, both approaches remain isolated, as long as the taxonomic and functional information cannot be interrelated. Techniques like self-organizing maps (SOMs) have been applied to cluster metagenomes into taxon-specific bins in order to link biodiversity with functions, but have not been applied to broad-scale NGS-based metagenomics yet. Here, we provide a novel implementation, demonstrate its potential and practicability, and provide a web-based service for public usage. Evaluation with published data sets mimicking varyingly complex habitats resulted into classification specificities and sensitivities of close to 100% to above 90% from phylum to genus level for assemblies exceeding 8 kb for low and medium complexity data. When applied to five real-world metagenomes of medium complexity from direct pyrosequencing of marine subsurface waters, classifications of assemblies above 2.5 kb were in good agreement with fluorescence in situ hybridizations, indicating that biodiversity was mostly retained within the metagenomes, and confirming high classification specificities. This was validated by two protein-based classifications (PBCs) methods. SOMs were able to retrieve the relevant taxa down to the genus level, while surpassing PBCs in resolution. In order to make the approach accessible to a broad audience, we implemented a feature-rich web-based SOM application named TaxSOM, which is freely available at http://www.megx.net/toolbox/taxsom. TaxSOM can classify reads or assemblies exceeding 2.5 kb with high accuracy and thus assists in linking biodiversity and functions in metagenome studies, which is a precondition to study microbial ecology in a holistic fashion.
ERIC Educational Resources Information Center
Lysack, Catherine; Kaufert, Joseph
1994-01-01
This paper explores the origins, differences, and similarities of community-based rehabilitation, which developed in southern countries, and independent living, which developed in northern countries, for persons with disabilities. Although both approaches share a broad definition of rehabilitation and values emphasizing community and consumer…
Automatic Syllabification in English: A Comparison of Different Algorithms
ERIC Educational Resources Information Center
Marchand, Yannick; Adsett, Connie R.; Damper, Robert I.
2009-01-01
Automatic syllabification of words is challenging, not least because the syllable is not easy to define precisely. Consequently, no accepted standard algorithm for automatic syllabification exists. There are two broad approaches: rule-based and data-driven. The rule-based method effectively embodies some theoretical position regarding the…
ERIC Educational Resources Information Center
Blasco, Maribel
2015-01-01
The article proposes an approach, broadly inspired by culturally inclusive pedagogy, to facilitate international student academic adaptation based on rendering tacit aspects of local learning cultures explicit to international full degree students, rather than adapting them. Preliminary findings are presented from a focus group-based exploratory…
HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure.
Kwong, Peter D; Mascola, John R
2018-05-15
HIV-1 vaccine development has been stymied by an inability to induce broadly reactive neutralizing antibodies to the envelope (Env) trimer, the sole viral antigen on the virion surface. Antibodies isolated from HIV-1-infected donors, however, have been shown to recognize all major exposed regions of the prefusion-closed Env trimer, and an emerging understanding of the immunological and structural characteristics of these antibodies and the epitopes they recognize is enabling new approaches to vaccine design. Antibody lineage-based design creates immunogens that activate the naive ancestor-B cell of a target antibody lineage and that mature intermediate-B cells toward effective neutralization, with proof of principle achieved with select HIV-1-neutralizing antibody lineages in human-gene knock-in mouse models. Epitope-based vaccine design involves the engineering of sites of Env vulnerability as defined by the recognition of broadly neutralizing antibodies, with cross-reactive neutralizing antibodies elicited in animal models. Both epitope-based and antibody lineage-based HIV-1 vaccine approaches are being readied for human clinical trials. Published by Elsevier Inc.
ERIC Educational Resources Information Center
Bryant, Doug
This paper, titled "The Components of Emotional Intelligence and the Relationship to Sales Performance," presents two general approaches to studying emotional intelligence. The first is a broad model approach that considers abilities as well as a series of personality traits. The second is based on ability models. The possible correlation between…
A fast-paced delivery of approaches developed in EPA partnerships to enable effective inclusion of environmental and social resilience into hazard mitigation planning. This presentation will cover a broad spectrum, from 1) EPA’s role in mitigation, 2) what a Regional Resil...
Information Systems for Subject Specialists: A Multi-Modal Approach to Indexing and Classification.
ERIC Educational Resources Information Center
Swift, D.F.; And Others
A fundamental problem in the two broad approaches to indexing in the social sciences--providing structure using preferred terms, cross references, and groupings of sets of materials, or compiling a concordance of an author's terms based on occurrence, leaving users free to impose their own structure--is that different indexers and users focus on…
Evidence-Based Medicine and Child Mental Health Services: A Broad Approach to Evaluation is Needed.
ERIC Educational Resources Information Center
McGuire, Jacqueline Barnes; And Others
1997-01-01
Describes quasi-experimental designs to be used as alternatives to randomized controlled trials in decisions concerning clinical practice and policy-making in the child mental health field. Highlights importance of taking a systems-level approach to evaluation, and describes ways in which qualitative outcomes measures can be used to sensitively…
Nickel, Daniel V; Ruggiero, Michael T; Korter, Timothy M; Mittleman, Daniel M
2015-03-14
The temperature-dependent terahertz spectra of the partially-disordered and ordered phases of camphor (C10H16O) are measured using terahertz time-domain spectroscopy. In its partially-disordered phases, a low-intensity, extremely broad resonance is found and is characterized using both a phenomenological approach and an approach based on ab initio solid-state DFT simulations. These two descriptions are consistent and stem from the same molecular origin for the broad resonance: the disorder-localized rotational correlations of the camphor molecules. In its completely ordered phase(s), multiple lattice phonon modes are measured and are found to be consistent with those predicted using solid-state DFT simulations.
The adaptive, cut-cell Cartesian approach (warts and all)
NASA Technical Reports Server (NTRS)
Powell, Kenneth G.
1995-01-01
Solution-adaptive methods based on cutting bodies out of Cartesian grids are gaining popularity now that the ways of circumventing the accuracy problems associated with small cut cells have been developed. Researchers are applying Cartesian-based schemes to a broad class of problems now, and, although there is still development work to be done, it is becoming clearer which problems are best suited to the approach (and which are not). The purpose of this paper is to give a candid assessment, based on applying Cartesian schemes to a variety of problems, of the strengths and weaknesses of the approach as it is currently implemented.
Schwab-Reese, Laura M; Hovdestad, Wendy; Tonmyr, Lil; Fluke, John
2018-01-20
Collecting child maltreatment data is a complicated undertaking for many reasons. As a result, there is an interest by child maltreatment researchers to develop methodologies that allow for the triangulation of data sources. To better understand how social media and internet-based technologies could contribute to these approaches, we conducted a scoping review to provide an overview of social media and internet-based methodologies for health research, to report results of evaluation and validation research on these methods, and to highlight studies with potential relevance to child maltreatment research and surveillance. Many approaches were identified in the broad health literature; however, there has been limited application of these approaches to child maltreatment. The most common use was recruiting participants or engaging existing participants using online methods. From the broad health literature, social media and internet-based approaches to surveillance and epidemiologic research appear promising. Many of the approaches are relatively low cost and easy to implement without extensive infrastructure, but there are also a range of limitations for each method. Several methods have a mixed record of validation and sources of error in estimation are not yet understood or predictable. In addition to the problems relevant to other health outcomes, child maltreatment researchers face additional challenges, including the complex ethical issues associated with both internet-based and child maltreatment research. If these issues are adequately addressed, social media and internet-based technologies may be a promising approach to reducing some of the limitations in existing child maltreatment data. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Adcock, Robert S.; Schroeder, Chad E.; Chu, Yong-Kyu; Sotsky, Julie B.; Cramer, Daniel E.; Chilton, Paula M.; Song, Chisu; Anantpadma, Manu; Davey, Robert A.; Prodhan, Aminul I.; Yin, Xinmin; Zhang, Xiang
2016-01-01
Viral emergence and reemergence underscore the importance of developing efficacious, broad-spectrum antivirals. Here, we report the discovery of tetrahydrobenzothiazole-based compound 1, a novel, broad-spectrum antiviral lead that was optimized from a hit compound derived from a cytopathic effect (CPE)-based antiviral screen using Venezuelan equine encephalitis virus. Compound 1 showed antiviral activity against a broad range of RNA viruses, including alphaviruses, flaviviruses, influenza virus, and ebolavirus. Mechanism-of-action studies with metabolomics and molecular approaches revealed that the compound inhibits host pyrimidine synthesis and establishes an antiviral state by inducing a variety of interferon-stimulated genes (ISGs). Notably, the induction of the ISGs by compound 1 was independent of the production of type 1 interferons. The antiviral activity of compound 1 was cell type dependent with a robust effect observed in human cell lines and no observed antiviral effect in mouse cell lines. Herein, we disclose tetrahydrobenzothiazole compound 1 as a novel lead for the development of a broad-spectrum, antiviral therapeutic and as a molecular probe to study the mechanism of the induction of ISGs that are independent of type 1 interferons. PMID:27185801
Challenges in detecting drowsiness based on driver’s behavior
NASA Astrophysics Data System (ADS)
Triyanti, V.; Iridiastadi, H.
2017-12-01
Drowsiness while driving has been a critical issue within the context of transportation safety. A number of approaches have been developed to reduce the risks of drowsy drivers. The mechanisms in detecting fatigue and sleepiness while driving has been categorized into three broad approaches, including vehicle-based, physiological-based, and behavior-based approaches. This paper will discuss recent studies in recognizing drowsy drivers based on their behaviors, particularly changes in eyes and facial characteristics. This paper will also address challenges in capturing aspects of natural expressions, driver responses, behavior, and task environment associated with sleepiness. Additionally, a number of technical aspects should be seriously considered, including correctly capturing face and eye characteristics from unwanted movements, unsuitable task environments, technological limitations, and individual differences.
ERIC Educational Resources Information Center
Landry, David J.; Lindberg, Laura Duberstein; Gemmill, Alison; Boonstra, Heather; Finer, Lawrence B.
2011-01-01
This article reviews the role of faith- and community-based organizations in providing comprehensive sexuality education for adolescents in the United States. To gather information about these organizations, a broad approach was used that included a formal literature review, systematic searches through organizational Web sites, and the convening…
ERIC Educational Resources Information Center
Cheng, Yin Cheong; Yuen, Timothy W. W.
2017-01-01
Purpose: The purpose of this paper is to contribute to the worldwide discussion of conceptualization, multiple functions and management of national education in an era of globalisation by proposing a new comprehensive framework for research, policy analysis and practical implementation. Design/Methodology/Approach: Based on a review of the…
Passive vibration control: a structure–immittance approach
Zhang, Sara Ying; Neild, Simon A.
2017-01-01
Linear passive vibration absorbers, such as tuned mass dampers, often contain springs, dampers and masses, although recently there has been a growing trend to employ or supplement the mass elements with inerters. When considering possible configurations with these elements broadly, two approaches are normally used: one structure-based and one immittance-based. Both approaches have their advantages and disadvantages. In this paper, a new approach is proposed: the structure–immittance approach. Using this approach, a full set of possible series–parallel networks with predetermined numbers of each element type can be represented by structural immittances, obtained via a proposed general formulation process. Using the structural immittances, both the ability to investigate a class of absorber possibilities together (advantage of the immittance-based approach), and the ability to control the complexity, topology and element values in resulting absorber configurations (advantages of the structure-based approach) are provided at the same time. The advantages of the proposed approach are demonstrated through two case studies on building vibration suppression and automotive suspension design, respectively. PMID:28588407
Passive vibration control: a structure-immittance approach.
Zhang, Sara Ying; Jiang, Jason Zheng; Neild, Simon A
2017-05-01
Linear passive vibration absorbers, such as tuned mass dampers, often contain springs, dampers and masses, although recently there has been a growing trend to employ or supplement the mass elements with inerters. When considering possible configurations with these elements broadly, two approaches are normally used: one structure-based and one immittance-based. Both approaches have their advantages and disadvantages. In this paper, a new approach is proposed: the structure-immittance approach. Using this approach, a full set of possible series-parallel networks with predetermined numbers of each element type can be represented by structural immittances, obtained via a proposed general formulation process. Using the structural immittances, both the ability to investigate a class of absorber possibilities together (advantage of the immittance-based approach), and the ability to control the complexity, topology and element values in resulting absorber configurations (advantages of the structure-based approach) are provided at the same time. The advantages of the proposed approach are demonstrated through two case studies on building vibration suppression and automotive suspension design, respectively.
Passive vibration control: a structure-immittance approach
NASA Astrophysics Data System (ADS)
Zhang, Sara Ying; Jiang, Jason Zheng; Neild, Simon A.
2017-05-01
Linear passive vibration absorbers, such as tuned mass dampers, often contain springs, dampers and masses, although recently there has been a growing trend to employ or supplement the mass elements with inerters. When considering possible configurations with these elements broadly, two approaches are normally used: one structure-based and one immittance-based. Both approaches have their advantages and disadvantages. In this paper, a new approach is proposed: the structure-immittance approach. Using this approach, a full set of possible series-parallel networks with predetermined numbers of each element type can be represented by structural immittances, obtained via a proposed general formulation process. Using the structural immittances, both the ability to investigate a class of absorber possibilities together (advantage of the immittance-based approach), and the ability to control the complexity, topology and element values in resulting absorber configurations (advantages of the structure-based approach) are provided at the same time. The advantages of the proposed approach are demonstrated through two case studies on building vibration suppression and automotive suspension design, respectively.
Developing an evidence-based approach to Public Health Nutrition: translating evidence into policy.
Margetts, B; Warm, D; Yngve, A; Sjöström, M
2001-12-01
The aim of this paper is to highlight the importance of an evidence-based approach to the development, implementation and evaluation of policies aimed at improving nutrition-related health in the population. Public Health Nutrition was established to realise a population-level approach to the prevention of the major nutrition-related health problems world-wide. The scope is broad and integrates activity from local, national, regional and international levels. The aim is to inform and develop coherent and effective policies that address the key rate-limiting steps critical to improving nutrition-related public health. This paper sets out the rationale for an evidence-based approach to Public Health Nutrition developed under the umbrella of the European Network for Public Health Nutrition.
ERIC Educational Resources Information Center
Fang, Jun
2012-01-01
Two critical issues are of great concern in engineering education today: the increasingly broad requirements for 21st-century engineers and the lack of effective instructional approaches needed to produce students who meet the requirements. However, pedagogical approaches in engineering have remained relatively unchanged for the last 40 years and…
ERIC Educational Resources Information Center
Donnelly, David S.
2013-01-01
This study employed a design-based research methodology to develop a theoretically sound approach for designing instructional treatments. The instruction of interest addressed the broad issue of physician wellness among medical school faculty, with particular emphasis on physician self-diagnosis and self-care. The theoretically sound approach…
ERIC Educational Resources Information Center
Cheng, Liang; Zhang, Wen; Wang, Jiechen; Li, Manchun; Zhong, Lishan
2014-01-01
Geographic information science (GIS) features a wide range of disciplines and has broad applicability. Challenges associated with rapidly developing GIS technology and the currently limited teaching and practice materials hinder universities from cultivating highly skilled GIS graduates. Based on the idea of "small core, big network," a…
Effectiveness and Accountability of the Inquiry-Based Methodology in Middle School Science
ERIC Educational Resources Information Center
Hardin, Cade
2009-01-01
When teaching science, the time allowed for students to make discoveries on their own through the inquiry method directly conflicts with the mandated targets of a broad spectrum of curricula. Research shows that using an inquiry-based approach can encourage student motivation and increase academic achievement (Wolf & Fraser, 2008, Bryant, 2006,…
ERIC Educational Resources Information Center
Dymnicki, Allison B.; Weissberg, Roger P.; Henry, David B.
2011-01-01
Several recent meta-analyses of universal school-based violence prevention studies indicate the overall positive impacts of these approaches on aggression. These studies, however, assess impacts on broadly defined measures of aggression. Furthermore, little research has analyzed the mechanisms through which these programs attempt to reduce overt…
Broad-based visual benefits from training with an integrated perceptual-learning video game.
Deveau, Jenni; Lovcik, Gary; Seitz, Aaron R
2014-06-01
Perception is the window through which we understand all information about our environment, and therefore deficits in perception due to disease, injury, stroke or aging can have significant negative impacts on individuals' lives. Research in the field of perceptual learning has demonstrated that vision can be improved in both normally seeing and visually impaired individuals, however, a limitation of most perceptual learning approaches is their emphasis on isolating particular mechanisms. In the current study, we adopted an integrative approach where the goal is not to achieve highly specific learning but instead to achieve general improvements to vision. We combined multiple perceptual learning approaches that have individually contributed to increasing the speed, magnitude and generality of learning into a perceptual-learning based video-game. Our results demonstrate broad-based benefits of vision in a healthy adult population. Transfer from the game includes; improvements in acuity (measured with self-paced standard eye-charts), improvement along the full contrast sensitivity function, and improvements in peripheral acuity and contrast thresholds. The use of this type of this custom video game framework built up from psychophysical approaches takes advantage of the benefits found from video game training while maintaining a tight link to psychophysical designs that enable understanding of mechanisms of perceptual learning and has great potential both as a scientific tool and as therapy to help improve vision. Copyright © 2014 Elsevier B.V. All rights reserved.
Wöller, Wolfgang; Leichsenring, Falk; Leweke, Frank; Kruse, Johannes
2012-01-01
In this article, the authors present a psychodynamically oriented psychotherapy approach for posttraumatic stress disorder (PTSD) related to childhood abuse. This neurobiologically informed, phase-oriented treatment approach, which has been developed in Germany during the past 20 years, takes into account the broad comorbidity and the large degree of ego-function impairment typically found in these patients. Based on a psychodynamic relationship orientation, this treatment integrates a variety of trauma-specific imaginative and resource-oriented techniques. The approach places major emphasis on the prevention of vicarious traumatization. The authors are presently planning to test the approach in a randomized controlled trial aimed at strengthening the evidence base for psychodynamic psychotherapy in PTSD.
Guide Lines for Evaluation of Continuing Education Programs in Mental Health.
ERIC Educational Resources Information Center
Miller, Norma; And Others
Suggestions for program administrators and training program directors to develop comprehensive plans based on principles of community involvement, education, administration and finance, and the disciplines being taught are broadly outlined. Three accompanying charts illustrate approach to evaluation planning. (NF)
A Functional Approach to the Assessment of Language Skills
ERIC Educational Resources Information Center
Jakobovits, Leon A.
1969-01-01
Argues for language tests based on a view of linguistic competence broad enough to recognize the importance of social-psychological factors in the use of language. Paper prepared for a conference on language testing at Idyllwild, California, November 7-8, 1968. (FWB)
Weber, Marc; Teeling, Hanno; Huang, Sixing; Waldmann, Jost; Kassabgy, Mariette; Fuchs, Bernhard M; Klindworth, Anna; Klockow, Christine; Wichels, Antje; Gerdts, Gunnar; Amann, Rudolf; Glöckner, Frank Oliver
2011-01-01
Next-generation sequencing (NGS) technologies have enabled the application of broad-scale sequencing in microbial biodiversity and metagenome studies. Biodiversity is usually targeted by classifying 16S ribosomal RNA genes, while metagenomic approaches target metabolic genes. However, both approaches remain isolated, as long as the taxonomic and functional information cannot be interrelated. Techniques like self-organizing maps (SOMs) have been applied to cluster metagenomes into taxon-specific bins in order to link biodiversity with functions, but have not been applied to broad-scale NGS-based metagenomics yet. Here, we provide a novel implementation, demonstrate its potential and practicability, and provide a web-based service for public usage. Evaluation with published data sets mimicking varyingly complex habitats resulted into classification specificities and sensitivities of close to 100% to above 90% from phylum to genus level for assemblies exceeding 8 kb for low and medium complexity data. When applied to five real-world metagenomes of medium complexity from direct pyrosequencing of marine subsurface waters, classifications of assemblies above 2.5 kb were in good agreement with fluorescence in situ hybridizations, indicating that biodiversity was mostly retained within the metagenomes, and confirming high classification specificities. This was validated by two protein-based classifications (PBCs) methods. SOMs were able to retrieve the relevant taxa down to the genus level, while surpassing PBCs in resolution. In order to make the approach accessible to a broad audience, we implemented a feature-rich web-based SOM application named TaxSOM, which is freely available at http://www.megx.net/toolbox/taxsom. TaxSOM can classify reads or assemblies exceeding 2.5 kb with high accuracy and thus assists in linking biodiversity and functions in metagenome studies, which is a precondition to study microbial ecology in a holistic fashion. PMID:21160538
Glycolysis-related proteins are broad spectrum vaccine candidates against aquacultural pathogens.
Liu, Xiaohong; Sun, Jiamin; Wu, Haizhen
2017-07-05
Reverse vaccinology (RV) has become a popular method for developing vaccines. Although Edwardsiella tarda is deemed to be an important fish pathogen, so far, no reports have used a genome-based approach to screen vaccine candidates against E. tarda. In the current study, protective antigens of E. tarda were screened using RV. Large-scale cloning, expression and purification of potential candidates were carried out, and their immunoprotective potential was evaluated. A candidate fructose-bisphosphate aldolase (FBA) exhibited broad spectrum protection, as did another glycolysis-related protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which we reported previously, indicating the potential of other glycolysis-related proteins of E. tarda as broad spectrum protective antigens. In total, half (5 out 10) of these proteins showed prominent immunoprotective potential. Therefore, we suggest that glycolysis-related proteins are a class of potential broad spectrum protective antigens and that these proteins should be preferentially selected. Copyright © 2017 Elsevier Ltd. All rights reserved.
Strategies to induce broadly protective antibody responses to viral glycoproteins.
Krammer, F
2017-05-01
Currently, several universal/broadly protective influenza virus vaccine candidates are under development. Many of these vaccines are based on strategies to induce protective antibody responses against the surface glycoproteins of antigenically and genetically diverse influenza viruses. These strategies might also be applicable to surface glycoproteins of a broad range of other important viral pathogens. Areas covered: Common strategies include sequential vaccination with divergent antigens, multivalent approaches, vaccination with glycan-modified antigens, vaccination with minimal antigens and vaccination with antigens that have centralized/optimized sequences. Here we review these strategies and the underlying concepts. Furthermore, challenges, feasibility and applicability to other viral pathogens are discussed. Expert commentary: Several broadly protective/universal influenza virus vaccine strategies will be tested in humans in the coming years. If successful in terms of safety and immunological readouts, they will move forward into efficacy trials. In the meantime, successful vaccine strategies might also be applied to other antigenically diverse viruses of concern.
Basic Visual Processes and Learning Disability.
ERIC Educational Resources Information Center
Leisman, Gerald
Representatives of a variety of disciplines concerned with either clinical or research problems in vision and learning disabilities present reviews and reports of relevant research and clinical approaches. Contributions are organized into four broad sections: basic processes, specific disorders, diagnosis of visually based problems in learning,…
In vitro and ex vivo strategies for intracellular delivery
NASA Astrophysics Data System (ADS)
Stewart, Martin P.; Sharei, Armon; Ding, Xiaoyun; Sahay, Gaurav; Langer, Robert; Jensen, Klavs F.
2016-10-01
Intracellular delivery of materials has become a critical component of genome-editing approaches, ex vivo cell-based therapies, and a diversity of fundamental research applications. Limitations of current technologies motivate development of next-generation systems that can deliver a broad variety of cargo to diverse cell types. Here we review in vitro and ex vivo intracellular delivery approaches with a focus on mechanisms, challenges and opportunities. In particular, we emphasize membrane-disruption-based delivery methods and the transformative role of nanotechnology, microfluidics and laboratory-on-chip technology in advancing the field.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.
2004-04-01
There is a need to develop approaches for assessing risk associated with acute exposures to a broad-range of chemical agents and to rapidly determine the potential implications to human health. Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants including heavy metals and pesticides. To advance the application of non-invasive biomonitoring a microfluidic/ electrochemical device has also been developed for the analysis of lead (Pb), using square wave anodic stripping voltammetry. Themore » system demonstrates a linear response over a broad concentration range (1 2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb-acetate. Appropriate pharmacokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for non-invasive biomonitoring can provide a sensitive, and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these non-invasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for accessing acute exposure and health risk.« less
Teacher in a Problem-Based Learning Environment--Jack of All Trades?
ERIC Educational Resources Information Center
Dahms, Mona Lisa; Spliid, Claus Monrad; Nielsen, Jens Frederik Dalsgaard
2017-01-01
Problem-based learning (PBL) is one among several approaches to active learning. Being a teacher in a PBL environment can, however, be a challenge because of the need to support students' learning within a broad "landscape of learning". In this article we will analyse the landscape of learning by use of the study activity model (SAM)…
Working towards the SDGs: measuring resilience from a practitioner's perspective
NASA Astrophysics Data System (ADS)
van Manen, S. M.; Both, M.
2015-12-01
The broad universal nature of the SDGs requires integrated approaches across development sectors and action at a variety of scales: from global to local. In humanitarian and development contexts, particularly at the local level, working towards these goals is increasingly approached through the concept of resilience. Resilience is broadly defined as the ability to minimise the impact of, cope with and recover from the consequences of shocks and stresses, both natural and manmade, without compromising long-term prospects. Key in this are the physical resources required and the ability to organise these prior to and during a crisis. However, despite the active debate on the theoretical foundations of resilience there is a comparative lack in the development of measurement approaches. The conceptual diversity of the few existing approaches further illustrates the complexity of operationalising the concept. Here we present a practical method to measure community resilience using a questionnaire composed of a generic set of household-level indicators. Rooted in the sustainable livelihoods approach it considers 6 domains: human, social, natural, economic, physical and political, and evaluates both resources and socio-cognitive factors. It is intended to be combined with more specific intervention-based questionnaires to systematically assess, monitor and evaluate the resilience of a community and the contribution of specific activities to resilience. Its use will be illustrated using a Haiti-based case study. The method presented supports knowledge-based decision making and impact monitoring. Furthermore, the evidence-based way of working contributes to accountability to a range of stakeholders and can be used for resource mobilisation. However, it should be noted that due to its inherent complexity and comprehensive nature there is no method or combination of methods and data types that can fully capture resilience in and across all of its facets, scales and domains.
The workshop was successful in advancing the state of the science, as well as in bringing together a broad base of experience and viewpoints to advance integrations of approaches to understanding basic chemical and physiological processes, toxicological effects and mechanisms, ec...
A Retrospective on Educational Planning in Comparative Education.
ERIC Educational Resources Information Center
Farrell, Joseph P.
1997-01-01
Defines and broadly traces the history of educational planning in both developing and industrialized capitalist nations. Discusses general approaches to educational planning (technical versus political planning, top-down versus bottom-up planning, and various theoretical bases); the contingency view of planning; case examples of planned,…
Nanotubule and Tour Molecule Based Molecular Electronics: Suggestion for a Hybrid Approach
NASA Technical Reports Server (NTRS)
Srivastava, Deepak; Saini, Subhash (Technical Monitor)
1998-01-01
Recent experimental and theoretical attempts and results indicate two distinct broad pathways towards future molecular electronic devices and architectures. The first is the approach via Tour type ladder molecules and their junctions which can be fabricated with solution phase chemical approaches. Second are fullerenes or nanotubules and their junctions which may have better conductance, switching and amplifying characteristics but can not be made through well controlled and defined chemical means. A hybrid approach combining the two pathways to take advantage of the characteristics of both is suggested. Dimension and scale of such devices would be somewhere in between isolated molecule and nanotubule based devices but it maybe possible to use self-assembly towards larger functional and logicalunits.
Chen, Chia-Yen; Lee, Phil H; Castro, Victor M; Minnier, Jessica; Charney, Alexander W; Stahl, Eli A; Ruderfer, Douglas M; Murphy, Shawn N; Gainer, Vivian; Cai, Tianxi; Jones, Ian; Pato, Carlos N; Pato, Michele T; Landén, Mikael; Sklar, Pamela; Perlis, Roy H; Smoller, Jordan W
2018-04-18
Bipolar disorder (BD) is a heritable mood disorder characterized by episodes of mania and depression. Although genomewide association studies (GWAS) have successfully identified genetic loci contributing to BD risk, sample size has become a rate-limiting obstacle to genetic discovery. Electronic health records (EHRs) represent a vast but relatively untapped resource for high-throughput phenotyping. As part of the International Cohort Collection for Bipolar Disorder (ICCBD), we previously validated automated EHR-based phenotyping algorithms for BD against in-person diagnostic interviews (Castro et al. Am J Psychiatry 172:363-372, 2015). Here, we establish the genetic validity of these phenotypes by determining their genetic correlation with traditionally ascertained samples. Case and control algorithms were derived from structured and narrative text in the Partners Healthcare system comprising more than 4.6 million patients over 20 years. Genomewide genotype data for 3330 BD cases and 3952 controls of European ancestry were used to estimate SNP-based heritability (h 2 g ) and genetic correlation (r g ) between EHR-based phenotype definitions and traditionally ascertained BD cases in GWAS by the ICCBD and Psychiatric Genomics Consortium (PGC) using LD score regression. We evaluated BD cases identified using 4 EHR-based algorithms: an NLP-based algorithm (95-NLP) and three rule-based algorithms using codified EHR with decreasing levels of stringency-"coded-strict", "coded-broad", and "coded-broad based on a single clinical encounter" (coded-broad-SV). The analytic sample comprised 862 95-NLP, 1968 coded-strict, 2581 coded-broad, 408 coded-broad-SV BD cases, and 3 952 controls. The estimated h 2 g were 0.24 (p = 0.015), 0.09 (p = 0.064), 0.13 (p = 0.003), 0.00 (p = 0.591) for 95-NLP, coded-strict, coded-broad and coded-broad-SV BD, respectively. The h 2 g for all EHR-based cases combined except coded-broad-SV (excluded due to 0 h 2 g ) was 0.12 (p = 0.004). These h 2 g were lower or similar to the h 2 g observed by the ICCBD + PGCBD (0.23, p = 3.17E-80, total N = 33,181). However, the r g between ICCBD + PGCBD and the EHR-based cases were high for 95-NLP (0.66, p = 3.69 × 10 -5 ), coded-strict (1.00, p = 2.40 × 10 -4 ), and coded-broad (0.74, p = 8.11 × 10 -7 ). The r g between EHR-based BD definitions ranged from 0.90 to 0.98. These results provide the first genetic validation of automated EHR-based phenotyping for BD and suggest that this approach identifies cases that are highly genetically correlated with those ascertained through conventional methods. High throughput phenotyping using the large data resources available in EHRs represents a viable method for accelerating psychiatric genetic research.
In-line interferometer for broadband near-field scanning optical spectroscopy.
Brauer, Jens; Zhan, Jinxin; Chimeh, Abbas; Korte, Anke; Lienau, Christoph; Gross, Petra
2017-06-26
We present and investigate a novel approach towards broad-bandwidth near-field scanning optical spectroscopy based on an in-line interferometer for homodyne mixing of the near field and a reference field. In scattering-type scanning near-field optical spectroscopy, the near-field signal is usually obscured by a large amount of unwanted background scattering from the probe shaft and the sample. Here we increase the light reflected from the sample by a semi-transparent gold layer and use it as a broad-bandwidth, phase-stable reference field to amplify the near-field signal in the visible and near-infrared spectral range. We experimentally demonstrate that this efficiently suppresses the unwanted background signal in monochromatic near-field measurements. For rapid acquisition of complete broad-bandwidth spectra we employ a monochromator and a fast line camera. Using this fast acquisition of spectra and the in-line interferometer we demonstrate the measurement of pure near-field spectra. The experimental observations are quantitatively explained by analytical expressions for the measured optical signals, based on Fourier decomposition of background and near field. The theoretical model and in-line interferometer together form an important step towards broad-bandwidth near-field scanning optical spectroscopy.
Keeping in Character: A Time-Tested Solution.
ERIC Educational Resources Information Center
Benninga, Jaques S.; Wynne, Edward A.
1998-01-01
Refutes Alfie Kohn's criticisms of modern character education programs in the February 1997 "Kappan." The basic structure of true "for character" education relies on an approach relevant for students of all ages, has been time-tested over 2,500 years, has broad public support, and has a valid research base. Kohn advocates…
New technologies and approaches in toxicity testing and risk assessment (ESOT)
The release of the National Research Council’s Report “Toxicity Testing in the 21st Century: A Vision and a Strategy” in 2007 initiated a broad-based movement in the toxicology community to re-think how toxicity testing and risk assessment are performed. Multiple efforts in the ...
Why Save Wilderness?--Fruits and Veggies!
ERIC Educational Resources Information Center
Kowalewski, David
2015-01-01
Why save wilderness? Environmental educators usually offer ecosystemic and aesthetic reasons, yet clearly this abstract approach has failed to resonate with the wider public. In this article I adopt a nutritional strategy based on a broad array of sources. Wild plant food, in terms of economics, ubiquity, and other measures, performs very well…
Embodied Computation: An Active-Learning Approach to Mobile Robotics Education
ERIC Educational Resources Information Center
Riek, L. D.
2013-01-01
This paper describes a newly designed upper-level undergraduate and graduate course, Autonomous Mobile Robots. The course employs active, cooperative, problem-based learning and is grounded in the fundamental computational problems in mobile robotics defined by Dudek and Jenkin. Students receive a broad survey of robotics through lectures, weekly…
Parental Attitudes Regarding School-Based Sexuality Education in Utah
ERIC Educational Resources Information Center
Steadman, Mindy; Crookston, Benjamin; Page, Randy; Hall, Cougar
2014-01-01
Sexuality education programs can be broadly categorized as either risk-avoidance or risk-reduction approaches. Health educators in Utah public schools must teach a state mandated risk-avoidance curriculum which prohibits the advocacy or encouragement of contraception. Multiple national surveys indicate that parents prefer a risk-reduction approach…
Effective public health policy should not be based solely on clinical, individualbased
information, but requires a broad characterization of human health conditions
across large geographic areas. For the most part, the necessary monitoring of human
health to ...
ERIC Educational Resources Information Center
Avis, Joan P.
1987-01-01
Proposes collaborative counseling as a comprehensive definition of adult counseling. Presents rationale for definition based on broad implications for counselors of adult development and life transitions literature. Discusses three perspectives as a conceptual framework for defining the phenomenology of the counselor of adults. Outlines elements…
Challenging Students' Perceptions of Sustainability Using an Earth Systems Science Approach
ERIC Educational Resources Information Center
Clark, Ian F.; Zeegers, Yvonne
2015-01-01
This study investigated whether an Earth Systems-based course focused on raising postgraduate students' awareness of sustainability, from a systems-thinking perspective, would produce graduates with commitment to drive the sustainability agenda forward with a broad perspective. It investigated students' pre and post-course perceptions of…
A Thematic Instruction Approach to Teaching Technology and Engineering
ERIC Educational Resources Information Center
Moyer, Courtney D.
2016-01-01
Thematic instruction offers flexible opportunities to engage students with real-world experiences in the technology and engineering community. Whether used in a broad unifying theme or specific project-based theme, research has proven that thematic instruction has the capacity to link cross-curricular subjects, facilitate active learning, and…
Helping Students Overcome Depression and Anxiety: A Practical Guide. Second Edition
ERIC Educational Resources Information Center
Merrell, Kenneth W.
2008-01-01
This guide provides expert information and clear-cut strategies for assessing and treating internalizing problems in school settings. More than 40 specific psychoeducational and psychosocial intervention techniques are detailed, with a focus on approaches that are evidence based, broadly applicable, and easy to implement. Including 26…
Effects of Virtual Manipulatives with Different Approaches on Students' Knowledge of Slope
ERIC Educational Resources Information Center
Demir, Mustafa
2018-01-01
Virtual Manipulatives (VMs) are computer-based, dynamic, and visual representations of mathematical concepts, provide interactive learning environments to advance mathematics instruction (Moyer et al., 2002). Despite their broad use, few research explored the integration of VMs into mathematics instruction (Moyer-Packenham & Westenskow, 2013).…
ERIC Educational Resources Information Center
Danielsen, Dina; Bruselius-Jensen, Maria; Laitsch, Daniel
2017-01-01
Health promotion and education researchers and practitioners advocate for more democratic approaches to school-based health education, including participatory teaching methods and the promotion of a broad and positive concept of health and health knowledge, including aspects of the German educational concept of "bildung." Although…
Research in Distance Education: A System Modeling Approach.
ERIC Educational Resources Information Center
Saba, Farhad; Twitchell, David
This demonstration of the use of a computer simulation research method based on the System Dynamics modeling technique for studying distance education reviews research methods in distance education, including the broad categories of conceptual and case studies, and presents a rationale for the application of systems research in this area. The…
School-based programs to reduce sexual risk-taking behaviors.
Kirby, D
1992-09-01
This article reviews the major approaches implemented during the last two decades to reduce sexual risk-taking behaviors, examines their evidence for success, and provides several recommendations for effective programs and program evaluations. This article does not discuss more broad-based sexuality education programs which address sexuality in a broader context. Instead, this article focuses primarily on programs that educators believed would reduce unprotected sexual intercourse.
Introduction: evidence-based action in humanitarian crises.
Dijkzeul, Dennis; Hilhorst, Dorothea; Walker, Peter
2013-07-01
This introductory paper sets the stage for this special issue of Disasters on evidence-based action in humanitarian crises. It reviews definition(s) of evidence and it examines the different disciplinary and methodological approaches to collecting and analysing evidence. In humanitarian action, the need for evidence-based approaches sometimes is viewed in tension with a principled approach, often unnecessarily. Choosing appropriate research methods depends on the objectives of the researcher, in particular whether the research focuses on the intervention and/or the context and the length and complexity of the causal chains involved. The paper concludes by defining some trends in evidence-based approaches in crises: the move away from inputs and outputs of humanitarian action towards outcomes and impacts; the shift towards a higher degree of partnerships in research, and the participation of users and target groups; and the acceptance of a broad array of approaches to establish evidence. © 2013 The Author(s). Journal compilation © Overseas Development Institute, 2013.
Steinsbekk, Kristin Solum; Kåre Myskja, Bjørn; Solberg, Berge
2013-01-01
In the endeavour of biobank research there is dispute concerning what type of consent and which form of donor–biobank relationship meet high ethical standards. Up until now, a ‘broad consent' model has been used in many present-day biobank projects. However it has been, by some scholars, deemed as a pragmatic, and not an acceptable ethical solution. Calls for change have been made on the basis of avoidance of paternalism, intentions to fulfil the principle of autonomy, wish for increased user participation, a questioning of the role of experts and ideas advocating reduction of top–down governance. Recently, an approach termed ‘dynamic consent' has been proposed to meet such challenges. Dynamic consent uses modern communication strategies to inform, involve, offer choices and last but not the least obtain consent for every research projects based on biobank resources. At first glance dynamic consent seems appealing, and we have identified six claims of superiority of this model; claims pertaining to autonomy, information, increased engagement, control, social robustness and reciprocity. However, after closer examination, there seems to be several weaknesses with a dynamic consent approach; among others the risk of inviting people into the therapeutic misconception as well as individualizing the ethical review of research projects. When comparing the two models, broad consent still holds and can be deemed a good ethical solution for longitudinal biobank research. Nevertheless, there is potential for improvement in the broad model, and criticism can be met by adapting some of the modern communication strategies proposed in the dynamic consent approach. PMID:23299918
Sohl, Terry L.; Dornbierer, Jordan; Wika, Steve; Sayler, Kristi L.; Quenzer, Robert
2017-01-01
Land use and land cover (LULC) change occurs at a local level within contiguous ownership and management units (parcels), yet LULC models primarily use pixel-based spatial frameworks. The few parcel-based models being used overwhelmingly focus on small geographic areas, limiting the ability to assess LULC change impacts at regional to national scales. We developed a modified version of the Forecasting Scenarios of land use change model to project parcel-based agricultural change across a large region in the United States Great Plains. A scenario representing an agricultural biofuel scenario was modeled from 2012 to 2030, using real parcel boundaries based on contiguous ownership and land management units. The resulting LULC projection provides a vastly improved representation of landscape pattern over existing pixel-based models, while simultaneously providing an unprecedented combination of thematic detail and broad geographic extent. The conceptual approach is practical and scalable, with potential use for national-scale projections.
Rash Decisions: An Approach to Dangerous Rashes Based on Morphology.
Santistevan, Jamie; Long, Brit; Koyfman, Alex
2017-04-01
Rash is a common complaint in the emergency department. Many causes of rash are benign; however, some patients may have a life-threatening diagnosis. This review will present an algorithmic approach to rashes, focusing on life-threatening causes of rash in each category. Rash is common, with a wide range of etiologies. The differential is broad, consisting of many conditions that are self-resolving. However, several conditions associated with rash are life threatening. Several keys can be utilized to rapidly diagnose and manage these deadly rashes. Thorough history and physical examination, followed by consideration of red flags, are essential. This review focuses on four broad categories based on visual and tactile characteristic patterns of rashes: petechial/purpuric, erythematous, maculopapular, and vesiculobullous. Rashes in each morphologic group will be further categorized based on clinical features such as the presence or absence of fever and distribution of skin lesions. Rashes can be divided into petechial/purpuric, erythematous, maculopapular, and vesiculobullous. After this differentiation, the presence of fever and systemic signs of illness should be assessed. Through the breakdown of rashes into these classes, emergency providers can ensure deadly conditions are considered. Published by Elsevier Inc.
Optimizing technology investments: a broad mission model approach
NASA Technical Reports Server (NTRS)
Shishko, R.
2003-01-01
A long-standing problem in NASA is how to allocate scarce technology development resources across advanced technologies in order to best support a large set of future potential missions. Within NASA, two orthogonal paradigms have received attention in recent years: the real-options approach and the broad mission model approach. This paper focuses on the latter.
A dryland ecologist’s mid-career retrospective on LTER and the science-management interface
USDA-ARS?s Scientific Manuscript database
My association with the LTER Program has encouraged a multidisciplinary scientific approach emphasizing broad spatial scales and site-based knowledge. It also provides a solid basis from which to link science and management. In my position as a federal research scientist, I do not teach university c...
The Role of School Health Instruction in Preventing Injury: Making It Work.
ERIC Educational Resources Information Center
Weiler, Robert M.
Reducing the incidence and severity of child and adolescent injuries requires a multifaceted approach involving broad-based health and social service agencies, including schools. Recognition of the need for injury prevention education began with the Industrial Revolution in the 1900s, and safety education was developed as a unit of health…
ERIC Educational Resources Information Center
Allen, Laura B.; Tsao, Jennie C. I.; Seidman, Laura C.; Ehrenreich-May, Jill; Zeltzer, Lonnie K.
2012-01-01
Chronic pain disorders represent a significant public health concern, particularly for children and adolescents. High rates of comorbid anxiety and unipolar mood disorders often complicate psychological interventions for chronic pain. Unified treatment approaches, based on emotion regulation skills, are applicable to a broad range of emotional…
ERIC Educational Resources Information Center
Boufoy-Bastick, Beatrice
School curricula reflect the sociocultural values held by society. As such, curricula may adopt: (1) a philosophically humanistic, individual-sensitive orientation, or (2) an economically-driven, social development orientation. This first orientation supports self-realization and prioritizes a broad-based and multidisciplinary school curriculum.…
ERIC Educational Resources Information Center
Marchel, Carol A.; Green, Susan K
2014-01-01
Increased use of field-based teacher preparation offers important opportunities to develop skills with diverse learners. However, limited focus on theoretical content restricts understanding and generalization of well-proven theoretical approaches, resulting in fragmented field applications unlikely to result in broad application. Inspired by Kurt…
ERIC Educational Resources Information Center
Larbi-Apau, Josephine A.; Moseley, James L.
2008-01-01
This article provides a comprehensive approach to careful review and evaluation of the implementation of performance training intervention. It discusses the E[superscript 3] process for success, a basic framework for evaluating the implementation phase of a training program implemented as a broad-based performance improvement strategy. The intent…
The Curriculum Workshop: A Place for Deliberative Inquiry and Teacher Professional Learning
ERIC Educational Resources Information Center
Hansen, Klaus-Henning
2008-01-01
In this article, the curriculum workshop (CW) is elaborated as an approach to professional learning, deliberation and inquiry. It offers a comprehensive framework for school-based deliberation and inquiry, is rooted in curriculum theory, promises a broad range of applications in teacher education and provides tools to assess the trustworthiness of…
Implementing Collaborative Learning across the Engineering Curriculum
ERIC Educational Resources Information Center
Ralston, Patricia A. S.; Tretter, Thomas R.; Kendall-Brown, Marie
2017-01-01
Active and collaborative teaching methods increase student learning, and it is broadly accepted that almost any active or collaborative approach will improve learning outcomes as compared to lecture. Yet, large numbers of faculty have not embraced these methods. Thus, the challenge to encourage evidence-based change in teaching is not only how to…
The Introductory Anthropology Course: A Multi-Track Approach for Community College Instruction
ERIC Educational Resources Information Center
Foster, Daniel J.
1976-01-01
Asserts that the most basic types of understandings that students should gain from the beginning anthropology course could be grouped into two broad categories based upon two very important precepts of anthropology: overcoming anthropocentrism and combating ethnocentrism. Using this as a guide, two lists of course objectives were compiled and the…
A Framework to Embed Communication Skills across the Curriculum: A Design-Based Research Approach
ERIC Educational Resources Information Center
Johnson, Steve; Veitch, Sarah; Dewiyanti, Silvia
2015-01-01
There is widespread recognition that universities are now delivering higher education to diverse student populations with very different needs and aspirations from the more traditional cohorts of the past. In order to prepare students for a broad range of employment opportunities, universities are also fostering the development of "graduate…
Gifts of the Spirit: Multiple Intelligences in Religious Education. Second Edition.
ERIC Educational Resources Information Center
Nuzzi, Ronald
This booklet provides practical direction for religious educators that they might effectively teach heterogeneous groups of learners by employing a broad range of teaching/learning approaches while keeping in the forefront the importance of basing practice on sound theory. The booklet begins with a clear explication of the essential attributes of…
User Situational Context: An Essential Challenge to Context Awareness
ERIC Educational Resources Information Center
Mowafi, Yaser Abdallah
2009-01-01
Existing research on context and context awareness has broadly focused on the technical aspects of context acquisition and interpretation of users' surroundings, also called physical or sensor-based context. Such an approach has lacked from reconciling the perception of real-world context exhibited by humans, also known as user context, and…
ERIC Educational Resources Information Center
Najor, Michele A.; Motschall, Melissa
2001-01-01
Describes how the authors use a broad-based, client-centered model to teach an introductory course in public relations, integrating writing assignments for "clients" into course topics, which include history, ethics, theory, research, program planning, publicity, crisis management, and evaluation methods. Discusses course objectives, and notes…
Modeling current climate conditions for forest pest risk assessment
Frank H. Koch; John W. Coulston
2010-01-01
Current information on broad-scale climatic conditions is essential for assessing potential distribution of forest pests. At present, sophisticated spatial interpolation approaches such as the Parameter-elevation Regressions on Independent Slopes Model (PRISM) are used to create high-resolution climatic data sets. Unfortunately, these data sets are based on 30-year...
MLeXAI: A Project-Based Application-Oriented Model
ERIC Educational Resources Information Center
Russell, Ingrid; Markov, Zdravko; Neller, Todd; Coleman, Susan
2010-01-01
Our approach to teaching introductory artificial intelligence (AI) unifies its diverse core topics through a theme of machine learning, and emphasizes how AI relates more broadly with computer science. Our work, funded by a grant from the National Science Foundation, involves the development, implementation, and testing of a suite of projects that…
A new multicriteria risk mapping approach based on a multiattribute frontier concept
Denys Yemshanov; Frank H. Koch; Yakov Ben-Haim; Marla Downing; Frank Sapio; Marty Siltanen
2013-01-01
Invasive species risk maps provide broad guidance on where to allocate resources for pest monitoring and regulation, but they often present individual risk components (such as climatic suitability, host abundance, or introduction potential) as independent entities. These independent risk components are integrated using various multicriteria analysis techniques that...
Dissecting disease entities out of the broad spectrum of bipolar-disorders.
Levine, Joseph; Toker, Lilach; Agam, Galila
2018-01-01
The etiopathology of bipolar disorders is yet unraveled and new avenues should be pursued. One such avenue may be based on the assumption that the bipolar broad spectrum includes, among others, an array of rare medical disease entities. Towards this aim we propose a dissecting approach based on a search for rare medical diseases with known etiopathology which also exhibit bipolar disorders symptomatology. We further suggest that the etiopathologic mechanisms underlying such rare medical diseases may also underlie a rare variant of bipolar disorder. Such an assumption may be further reinforced if both the rare medical disease and its bipolar clinical phenotype demonstrate a] a similar mode of inheritance (i.e, autosomal dominant); b] brain involvement; and c] data implicating that the etiopathological mechanisms underlying the rare diseases affect biological processes reported to be associated with bipolar disorders and their treatment. We exemplify our suggested approach by a rare case of autosomal dominant leucodystrophy, a disease entity exhibiting nuclear lamin B1 pathology also presenting bipolar symptomatology. Copyright © 2017 Elsevier B.V. All rights reserved.
Vincenot, Christian E
2018-03-14
Progress in understanding and managing complex systems comprised of decision-making agents, such as cells, organisms, ecosystems or societies, is-like many scientific endeavours-limited by disciplinary boundaries. These boundaries, however, are moving and can actively be made porous or even disappear. To study this process, I advanced an original bibliometric approach based on network analysis to track and understand the development of the model-based science of agent-based complex systems (ACS). I analysed research citations between the two communities devoted to ACS research, namely agent-based (ABM) and individual-based modelling (IBM). Both terms refer to the same approach, yet the former is preferred in engineering and social sciences, while the latter prevails in natural sciences. This situation provided a unique case study for grasping how a new concept evolves distinctly across scientific domains and how to foster convergence into a universal scientific approach. The present analysis based on novel hetero-citation metrics revealed the historical development of ABM and IBM, confirmed their past disjointedness, and detected their progressive merger. The separation between these synonymous disciplines had silently opposed the free flow of knowledge among ACS practitioners and thereby hindered the transfer of methodological advances and the emergence of general systems theories. A surprisingly small number of key publications sparked the ongoing fusion between ABM and IBM research. Beside reviews raising awareness of broad-spectrum issues, generic protocols for model formulation and boundary-transcending inference strategies were critical means of science integration. Accessible broad-spectrum software similarly contributed to this change. From the modelling viewpoint, the discovery of the unification of ABM and IBM demonstrates that a wide variety of systems substantiate the premise of ACS research that microscale behaviours of agents and system-level dynamics are inseparably bound. © 2018 The Author(s).
DOE Office of Scientific and Technical Information (OSTI.GOV)
Skurikhin, Alexei N
With increasing deployment of satellite imaging systems, only a small fraction of collected data can be subject to expert scrutiny. We present and evaluate a two-tier approach to broad area search for signs of anthropogenic activities in high-resolution commercial satellite imagery. The method filters image information using semantically oriented interest points by combining Harris corner detection and spatial pyramid matching. The idea is that anthropogenic structures, such as rooftop outlines, fence corners, road junctions, are locally arranged in specific angular relations to each other. They are often oriented at approximately right angles to each other (which is known as rectilinearitymore » relation). Detecting the rectilinearity provides an opportunity to highlight regions most likely to contain anthropogenic activity. This is followed by supervised classification of regions surrounding the detected corner points as man-made vs. natural scenes. We consider, in particular, a search for anthropogenic activities in uncluttered areas. In this paper, we proposed and evaluated a two-tier approach to broad area search for signs of anthropogenic activities. Results from experiments on high-resolution ({approx}0.6m) commercial satellite image data showed the potential applicability of this approach and its ability of achieving both high precision and recall rates. The main advantage of combining corner-based cueing with general object recognition is that the incorporation of domain specific knowledge even in its more general form, such as presence of comers, provides a useful cue to narrow the focus of search for signs of anthropogenic activities. Combination of comer based cueing with spatial pyramid matching addressed the issue of comer categorization. An important practical issue for further research is optimizing the balance between false positive and false negative rates. While the results presented in the paper are encouraging, the problem of an automated broad area search for signs of anthropogenic activities remains challenging.« less
Gene Therapy for Infectious Diseases
Bunnell, Bruce A.; Morgan, Richard A.
1998-01-01
Gene therapy is being investigated as an alternative treatment for a wide range of infectious diseases that are not amenable to standard clinical management. Approaches to gene therapy for infectious diseases can be divided into three broad categories: (i) gene therapies based on nucleic acid moieties, including antisense DNA or RNA, RNA decoys, and catalytic RNA moieties (ribozymes); (ii) protein approaches such as transdominant negative proteins and single-chain antibodies; and (iii) immunotherapeutic approaches involving genetic vaccines or pathogen-specific lymphocytes. It is further possible that combinations of the aforementioned approaches will be used simultaneously to inhibit multiple stages of the life cycle of the infectious agent. PMID:9457428
Alcohol expectancy multiaxial assessment: a memory network-based approach.
Goldman, Mark S; Darkes, Jack
2004-03-01
Despite several decades of activity, alcohol expectancy research has yet to merge measurement approaches with developing memory theory. This article offers an expectancy assessment approach built on a conceptualization of expectancy as an information processing network. The authors began with multidimensional scaling models of expectancy space, which served as heuristics to suggest confirmatory factor analytic dimensional models for entry into covariance structure predictive models. It is argued that this approach permits a relatively thorough assessment of the broad range of potential expectancy dimensions in a format that is very flexible in terms of instrument length and specificity versus breadth of focus. ((c) 2004 APA, all rights reserved)
In Vivo Histamine Optical Nanosensors
Cash, Kevin J.; Clark, Heather A.
2012-01-01
In this communication we discuss the development of ionophore based nanosensors for the detection and monitoring of histamine levels in vivo. This approach is based on the use of an amine-reactive, broad spectrum ionophore which is capable of recognizing and binding to histamine. We pair this ionophore with our already established nanosensor platform, and demonstrate in vitro and in vivo monitoring of histamine levels. This approach enables capturing rapid kinetics of histamine after injection, which are more difficult to measure with standard approaches such as blood sampling, especially on small research models. The coupling together of in vivo nanosensors with ionophores such as nonactin provide a way to generate nanosensors for novel targets without the difficult process of designing and synthesizing novel ionophores. PMID:23112690
In vivo histamine optical nanosensors.
Cash, Kevin J; Clark, Heather A
2012-01-01
In this communication we discuss the development of ionophore based nanosensors for the detection and monitoring of histamine levels in vivo. This approach is based on the use of an amine-reactive, broad spectrum ionophore which is capable of recognizing and binding to histamine. We pair this ionophore with our already established nanosensor platform, and demonstrate in vitro and in vivo monitoring of histamine levels. This approach enables capturing rapid kinetics of histamine after injection, which are more difficult to measure with standard approaches such as blood sampling, especially on small research models. The coupling together of in vivo nanosensors with ionophores such as nonactin provide a way to generate nanosensors for novel targets without the difficult process of designing and synthesizing novel ionophores.
Implicit dosimetry of microorganism photodynamic inactivation
NASA Astrophysics Data System (ADS)
Tamošiūnas, Mindaugas; Kuliešienė, Neringa; Daugelavičius, Rimantas
2017-12-01
Photosensitization based antibacterial treatment is efficient against a broad range of pathogens but it utilizes suboptimal dosimetry with an explicit (and very broad range) determination of sensitizer concentration, light dose and fluence rates. In this study we verified the implicit dosimetry approach for pathogen photodynamic treatment, employing protoporphyrin IX (ppIX) photobleaching to assess the killing efficacy against Staphylococcus aureus and Candida albicans cells. The results show that there was an increased kill of S. aureus and C. albicans at higher degree of ppIX fluorescence decay. Therefore ppIX photobleaching can be incorporated into the PDI dose metric offering to predict the pathogen killing efficacy during photodynamic treatment.
The 'retro-design' concept for novel kinase inhibitors.
Müller, Gerhard; Sennhenn, Peter C; Woodcock, Timothy; Neumann, Lars
2010-07-01
Protein kinases are among the most attractive therapeutic targets for a broad range of diseases. This feature review highlights and classifies the main design principles employed to generate active and selective kinase inhibitors. In particular, emphasis is focused on a fragment-based lead-generation approach, which constitutes a novel design method for developing type II kinase inhibitors with distinct binding kinetic attributes. This 'retro-design' strategy relies on a customized fragment library, and contrasts the traditional approach used in the design of type II inhibitors.
Solar heating and cooling technical data and systems analysis
NASA Technical Reports Server (NTRS)
Christensen, D. L.
1976-01-01
The acquisition and processing of selected parametric data for inclusion in a computerized Data Base using the Marshall Information Retrieval and Data System (MIRADS) developed by NASA-MSFC is discussed. This data base provides extensive technical and socioeconomic information related to solar energy heating and cooling on a national scale. A broadly based research approach was used to assist in the support of program management and the application of a cost-effective program for solar energy development and demonstration.
Identifying priority sites for low impact development (LID) in a mixed-use watershed
ABSTRACT: Low impact development (LID), a comprehensive land use planning and design approach with the goal of mitigating land development impacts to the environment, is increasingly being touted as an effective approach to lessen runoff and pollutant loadings to streams. Broad-s...
Clinical examination and physical assessment of hip joint-related pain in athletes.
Reiman, Michael P; Thorborg, Kristian
2014-11-01
Evidence-based clinical examination and assessment of the athlete with hip joint related pain is complex. It requires a systematic approach to properly differentially diagnose competing potential causes of athletic pain generation. An approach with an initial broad focus (and hence use of highly sensitive tests/measures) that then is followed by utilizing more specific tests/measures to pare down this imprecise differential diagnosis list is suggested. Physical assessment measures are then suggested to discern impairments, activity and participation restrictions for athletes with hip-join related pain, hence guiding the proper treatment approach. 5.
2011-07-19
multidomain methods, Discontinuous Galerkin methods, interfacial treatment ∗ Jorge A. Escobar-Vargas, School of Civil and Environmental Engineering, Cornell...Click here to view linked References 1. Introduction Geophysical flows exhibit a complex structure and dynamics over a broad range of scales that...hyperbolic problems, where the interfacial patching was implemented with an upwind scheme based on a modified method of characteristics. This approach
Can Family-Based Treatment of Anorexia Nervosa Be Manualized?
Lock, James; Le Grange, Daniel
2001-01-01
The authors report on the development of a manual for treating adolescents with anorexia nervosa modeled on a family-based intervention originating at the Maudsley Hospital in London. The manual provides the first detailed account of a clinical approach shown to be consistently efficacious in randomized clinical trials for this disorder. Manualized family therapy appears to be acceptable to therapists, patients, and families. Preliminary outcomes are comparable to what would be expected in clinically supervised sessions. These results suggest that through the use of this manual a valuable treatment approach can now be tested more broadly in controlled and uncontrolled settings. PMID:11696652
Effective progression of nuclear magnetic resonance-detected fragment hits.
Eaton, Hugh L; Wyss, Daniel F
2011-01-01
Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade as an alternate lead generation tool to HTS approaches. Several compounds have now progressed into the clinic which originated from a fragment-based approach, demonstrating the utility of this emerging field. While fragment hit identification has become much more routine and may involve different screening approaches, the efficient progression of fragment hits into quality lead series may still present a major bottleneck for the broadly successful application of FBDD. In our laboratory, we have extensive experience in fragment-based NMR screening (SbN) and the subsequent iterative progression of fragment hits using structure-assisted chemistry. To maximize impact, we have applied this approach strategically to early- and high-priority targets, and those struggling for leads. Its application has yielded a clinical candidate for BACE1 and lead series in about one third of the SbN/FBDD projects. In this chapter, we will give an overview of our strategy and focus our discussion on NMR-based FBDD approaches. Copyright © 2011 Elsevier Inc. All rights reserved.
Post-targeting strategy for ready-to-use targeted nanodelivery post cargo loading.
Zhu, J Y; Hu, J J; Zhang, M K; Yu, W Y; Zheng, D W; Wang, X Q; Feng, J; Zhang, X Z
2017-12-14
Based on boronate formation, this study reports a post-targeting methodology capable of readily installing versatile targeting modules onto a cargo-loaded nanoplatform in aqueous mediums. This permits the targeted nanodelivery of broad-spectrum therapeutics (drug/gene) in a ready-to-use manner while overcoming the PEGylation-dilemma that frequently occurs in conventional targeting approaches.
ERIC Educational Resources Information Center
Kadiam, Subhash Chandra Bose S. V.; Mohammed, Ahmed Ali; Nguyen, Duc T.
2010-01-01
In this paper, we describe an approach to analyze 2D truss/Frame/Beam structures under Flash-based environment. Stiffness Matrix Method (SMM) module was developed as part of ongoing projects on a broad topic "Students' Learning Improvements in Science, Technology, Engineering and Mathematics (STEM) Related Areas" at Old Dominion…
ERIC Educational Resources Information Center
Scigliano, John A.
1983-01-01
Presents a research-based marketing model consisting of an environmental scanning process, a series of marketing audits, and an information-processing scheme. Views the essential elements of college marketing as information flow; high-level, long-term commitment; diverse strategies; innovation; and a broad view of marketing. Includes a marketing…
ERIC Educational Resources Information Center
Muntinga, M. E.; Krajenbrink, V. Q.; Peerdeman, S. M.; Croiset, G.; Verdonk, P.
2016-01-01
Recent years have seen a rise in the efforts to implement diversity topics into medical education, using either a "narrow" or a "broad" definition of culture. These developments urge that outcomes of such efforts are systematically evaluated by mapping the curriculum for diversity-responsive content. This study was aimed at…
[Individual Progress Program for the Extremely Gifted Student in the Greater Seattle Area.
ERIC Educational Resources Information Center
Norsen, Barbara G.; Wick, Christine
The Individual Progress Program (IPP) is an approach designed to serve extremely advanced gifted students (grades 1 through 9) in the Seattle area. IPP is intended to meet students' unmet educational needs by allowing them to progress at their own accelerated pace through a broadly based curriculum while also pursuing interest areas. The program…
Information Seeking Research Needs Extension towards Tasks and Technology
ERIC Educational Resources Information Center
Järvelin, Kalervo; Ingwersen, Peter
2004-01-01
This paper discusses the research into information seeking and its directions at a general level. We approach this topic by analysis and argumentation based on past research in the domain. We begin by presenting a general model of information seeking and retrieval which is used to derive nine broad dimensions that are needed to analyze information…
The Child Development Specialist in a Mental Health Center. Position Paper.
ERIC Educational Resources Information Center
Ranzoni, Patricia Smith
A child development team in a children's services unit of a mental health center should: (1) formulate a broad philosophy of treatment for young child clients; (2) evaluate treatment approaches to determine the extent to which they facilitate or conflict with that philosophy; (3) assess inservice training needs to ensure competency-based service…
Although progress has been made with HTS (high throughput screening) in profiling biological activity (e.g., EPA’s ToxCast™), challenges arise interpreting HTS results in the context of adversity & converting HTS assay concentrations to equivalent human doses for the broad domain...
ERIC Educational Resources Information Center
Bates, Denise; Burman, Elizabeth; Ejike-King, Lacreisha; Rufyiri, Charlotte
2012-01-01
Healthy Transitions is a program of the University of Tennessee's Ready for the World initiative, a broad plan to transform campus culture and prepare students for the 21st century. Healthy Transitions partners the university with a local community of Burundian refugees. The university joined several community organizations interested in the…
Techniques for capturing expert knowledge - An expert systems/hypertext approach
NASA Technical Reports Server (NTRS)
Lafferty, Larry; Taylor, Greg; Schumann, Robin; Evans, Randy; Koller, Albert M., Jr.
1990-01-01
The knowledge-acquisition strategy developed for the Explosive Hazards Classification (EHC) Expert System is described in which expert systems and hypertext are combined, and broad applications are proposed. The EHC expert system is based on rapid prototyping in which primary knowledge acquisition from experts is not emphasized; the explosive hazards technical bulletin, technical guidance, and minimal interviewing are used to develop the knowledge-based system. Hypertext is used to capture the technical information with respect to four issues including procedural, materials, test, and classification issues. The hypertext display allows the integration of multiple knowlege representations such as clarifications or opinions, and thereby allows the performance of a broad range of tasks on a single machine. Among other recommendations, it is suggested that the integration of hypertext and expert systems makes the resulting synergistic system highly efficient.
Aminoff, Michael J
2008-05-13
The training of clinical neurologists is undergoing profound change. Increasing subspecialization within neurology, the widening separation of clinical neurology from other branches of internal medicine, limitations of exposure to training in internal medicine, mandated restrictions in working hours, and attempts to shorten the training period are likely to have adverse effects on the next generation of clinical neurologists. Despite the need for a broad base in general medicine, discussed here, the exposure of neurology trainees to general medical disorders is diminishing. An emphasis on an algorithmic approach to patient management rather than on educating residents to use their reasoning faculties when applying new techniques and knowledge to clinical practice may adversely affect patient care. Neurologists require broad-based training in neurology, internal medicine, and psychiatry, to ensure excellence in clinical practice. It is time to question again whether they are receiving the training that they need.
Chiba, Shuntaro; Ikeda, Kazuyoshi; Ishida, Takashi; Gromiha, M Michael; Taguchi, Y-H; Iwadate, Mitsuo; Umeyama, Hideaki; Hsin, Kun-Yi; Kitano, Hiroaki; Yamamoto, Kazuki; Sugaya, Nobuyoshi; Kato, Koya; Okuno, Tatsuya; Chikenji, George; Mochizuki, Masahiro; Yasuo, Nobuaki; Yoshino, Ryunosuke; Yanagisawa, Keisuke; Ban, Tomohiro; Teramoto, Reiji; Ramakrishnan, Chandrasekaran; Thangakani, A Mary; Velmurugan, D; Prathipati, Philip; Ito, Junichi; Tsuchiya, Yuko; Mizuguchi, Kenji; Honma, Teruki; Hirokawa, Takatsugu; Akiyama, Yutaka; Sekijima, Masakazu
2015-11-26
A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective.
Chiba, Shuntaro; Ikeda, Kazuyoshi; Ishida, Takashi; Gromiha, M. Michael; Taguchi, Y-h.; Iwadate, Mitsuo; Umeyama, Hideaki; Hsin, Kun-Yi; Kitano, Hiroaki; Yamamoto, Kazuki; Sugaya, Nobuyoshi; Kato, Koya; Okuno, Tatsuya; Chikenji, George; Mochizuki, Masahiro; Yasuo, Nobuaki; Yoshino, Ryunosuke; Yanagisawa, Keisuke; Ban, Tomohiro; Teramoto, Reiji; Ramakrishnan, Chandrasekaran; Thangakani, A. Mary; Velmurugan, D.; Prathipati, Philip; Ito, Junichi; Tsuchiya, Yuko; Mizuguchi, Kenji; Honma, Teruki; Hirokawa, Takatsugu; Akiyama, Yutaka; Sekijima, Masakazu
2015-01-01
A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective. PMID:26607293
Reliability analysis in the Office of Safety, Environmental, and Mission Assurance (OSEMA)
NASA Astrophysics Data System (ADS)
Kauffmann, Paul J.
1994-12-01
The technical personnel in the SEMA office are working to provide the highest degree of value-added activities to their support of the NASA Langley Research Center mission. Management perceives that reliability analysis tools and an understanding of a comprehensive systems approach to reliability will be a foundation of this change process. Since the office is involved in a broad range of activities supporting space mission projects and operating activities (such as wind tunnels and facilities), it was not clear what reliability tools the office should be familiar with and how these tools could serve as a flexible knowledge base for organizational growth. Interviews and discussions with the office personnel (both technicians and engineers) revealed that job responsibilities ranged from incoming inspection to component or system analysis to safety and risk. It was apparent that a broad base in applied probability and reliability along with tools for practical application was required by the office. A series of ten class sessions with a duration of two hours each was organized and scheduled. Hand-out materials were developed and practical examples based on the type of work performed by the office personnel were included. Topics covered were: Reliability Systems - a broad system oriented approach to reliability; Probability Distributions - discrete and continuous distributions; Sampling and Confidence Intervals - random sampling and sampling plans; Data Analysis and Estimation - Model selection and parameter estimates; and Reliability Tools - block diagrams, fault trees, event trees, FMEA. In the future, this information will be used to review and assess existing equipment and processes from a reliability system perspective. An analysis of incoming materials sampling plans was also completed. This study looked at the issues associated with Mil Std 105 and changes for a zero defect acceptance sampling plan.
Reliability analysis in the Office of Safety, Environmental, and Mission Assurance (OSEMA)
NASA Technical Reports Server (NTRS)
Kauffmann, Paul J.
1994-01-01
The technical personnel in the SEMA office are working to provide the highest degree of value-added activities to their support of the NASA Langley Research Center mission. Management perceives that reliability analysis tools and an understanding of a comprehensive systems approach to reliability will be a foundation of this change process. Since the office is involved in a broad range of activities supporting space mission projects and operating activities (such as wind tunnels and facilities), it was not clear what reliability tools the office should be familiar with and how these tools could serve as a flexible knowledge base for organizational growth. Interviews and discussions with the office personnel (both technicians and engineers) revealed that job responsibilities ranged from incoming inspection to component or system analysis to safety and risk. It was apparent that a broad base in applied probability and reliability along with tools for practical application was required by the office. A series of ten class sessions with a duration of two hours each was organized and scheduled. Hand-out materials were developed and practical examples based on the type of work performed by the office personnel were included. Topics covered were: Reliability Systems - a broad system oriented approach to reliability; Probability Distributions - discrete and continuous distributions; Sampling and Confidence Intervals - random sampling and sampling plans; Data Analysis and Estimation - Model selection and parameter estimates; and Reliability Tools - block diagrams, fault trees, event trees, FMEA. In the future, this information will be used to review and assess existing equipment and processes from a reliability system perspective. An analysis of incoming materials sampling plans was also completed. This study looked at the issues associated with Mil Std 105 and changes for a zero defect acceptance sampling plan.
Structure-based design of broadly protective group a streptococcal M protein-based vaccines.
Dale, James B; Smeesters, Pierre R; Courtney, Harry S; Penfound, Thomas A; Hohn, Claudia M; Smith, Jeremy C; Baudry, Jerome Y
2017-01-03
A major obstacle to the development of broadly protective M protein-based group A streptococcal (GAS) vaccines is the variability within the N-terminal epitopes that evoke potent bactericidal antibodies. The concept of M type-specific protective immune responses has recently been challenged based on the observation that multivalent M protein vaccines elicited cross-reactive bactericidal antibodies against a number of non-vaccine M types of GAS. Additionally, a new "cluster-based" typing system of 175M proteins identified a limited number of clusters containing closely related M proteins. In the current study, we used the emm cluster typing system, in combination with computational structure-based peptide modeling, as a novel approach to the design of potentially broadly protective M protein-based vaccines. M protein sequences (AA 16-50) from the E4 cluster containing 17 emm types of GAS were analyzed using de novo 3-D structure prediction tools and the resulting structures subjected to chemical diversity analysis to identify sequences that were the most representative of the 3-D physicochemical properties of the M peptides in the cluster. Five peptides that spanned the range of physicochemical attributes of all 17 peptides were used to formulate synthetic and recombinant vaccines. Rabbit antisera were assayed for antibodies that cross-reacted with E4 peptides and whole bacteria by ELISA and for bactericidal activity against all E4GAS. The synthetic vaccine rabbit antisera reacted with all 17 E4M peptides and demonstrated bactericidal activity against 15/17 E4GAS. A recombinant hybrid vaccine containing the same E4 peptides also elicited antibodies that cross-reacted with all E4M peptides. Comprehensive studies using structure-based design may result in a broadly protective M peptide vaccine that will elicit cluster-specific and emm type-specific antibody responses against the majority of clinically relevant emm types of GAS. Copyright © 2016 Elsevier Ltd. All rights reserved.
Janssen, Alisha; Boster, Aaron; Lee, HyunKyu; Patterson, Beth; Prakash, Ruchika Shaurya
2015-01-01
Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system that results in diffuse nerve damage and associated physical and cognitive impairments. Of the few comprehensive rehabilitation options that exist for populations with lower baseline cognitive functioning, those that have been successful at eliciting broad cognitive improvements have focused on a multimodal training approach, emphasizing complex cognitive processing that utilizes multiple domains simultaneously. The current study sought to determine the feasibility of an 8-week, hybrid-variable priority training (HVT) program, with a secondary aim to assess the success of this training paradigm at eliciting broad cognitive transfer effects. Capitalizing on the multimodal training modalities offered by the Space Fortress platform, we compared the HVT strategy-based intervention with a waitlist control group, to primarily assess skill acquisition and secondarily determine presence of cognitive transfer. Twenty-eight participants met inclusionary criteria for the study and were randomized to either training or waitlist control groups. To assess broad transfer effects, a battery of neuropsychological tests was administered pre- and post-intervention. The results indicated an overall improvement in skill acquisition and evidence for the feasibility of the intervention, but a lack of broad transfer to tasks of cognitive functioning. Participants in the training group, however, did show improvements on a measure of spatial short-term memory. The current investigation provided support for the feasibility of a multimodal training approach, using the HVT strategy, within the MS population, but lacked broad transfer to multiple domains of cognitive functioning. Future improvements to obtain greater cognitive transfer efficacy would include a larger sample size, a longer course of training to evoke greater game score improvement, the inclusion of only cognitively impaired individuals, and integration of subjective measures of improvement in addition to objective tests of cognitive performance.
A Nonparametric, Multiple Imputation-Based Method for the Retrospective Integration of Data Sets.
Carrig, Madeline M; Manrique-Vallier, Daniel; Ranby, Krista W; Reiter, Jerome P; Hoyle, Rick H
2015-01-01
Complex research questions often cannot be addressed adequately with a single data set. One sensible alternative to the high cost and effort associated with the creation of large new data sets is to combine existing data sets containing variables related to the constructs of interest. The goal of the present research was to develop a flexible, broadly applicable approach to the integration of disparate data sets that is based on nonparametric multiple imputation and the collection of data from a convenient, de novo calibration sample. We demonstrate proof of concept for the approach by integrating three existing data sets containing items related to the extent of problematic alcohol use and associations with deviant peers. We discuss both necessary conditions for the approach to work well and potential strengths and weaknesses of the method compared to other data set integration approaches.
Proteomics approaches advance our understanding of plant self-incompatibility response.
Sankaranarayanan, Subramanian; Jamshed, Muhammad; Samuel, Marcus A
2013-11-01
Self-incompatibility (SI) in plants is a genetic mechanism that prevents self-fertilization and promotes out-crossing needed to maintain genetic diversity. SI has been classified into two broad categories: the gametophytic self-incompatibility (GSI) and the sporophytic self-incompatibility (SSI) based on the genetic mechanisms involved in 'self' pollen rejection. Recent proteomic approaches to identify potential candidates involved in SI have shed light onto a number of previously unidentified mechanisms required for SI response. SI proteome research has progressed from the use of isoelectric focusing in early days to the latest third-generation technique of comparative isobaric tag for relative and absolute quantitation (iTRAQ) used in recent times. We will focus on the proteome-based approaches used to study self-incompatibility (GSI and SSI), recent developments in the field of incompatibility research with emphasis on SSI and future prospects of using proteomic approaches to study self-incompatibility.
A Nonparametric, Multiple Imputation-Based Method for the Retrospective Integration of Data Sets
Carrig, Madeline M.; Manrique-Vallier, Daniel; Ranby, Krista W.; Reiter, Jerome P.; Hoyle, Rick H.
2015-01-01
Complex research questions often cannot be addressed adequately with a single data set. One sensible alternative to the high cost and effort associated with the creation of large new data sets is to combine existing data sets containing variables related to the constructs of interest. The goal of the present research was to develop a flexible, broadly applicable approach to the integration of disparate data sets that is based on nonparametric multiple imputation and the collection of data from a convenient, de novo calibration sample. We demonstrate proof of concept for the approach by integrating three existing data sets containing items related to the extent of problematic alcohol use and associations with deviant peers. We discuss both necessary conditions for the approach to work well and potential strengths and weaknesses of the method compared to other data set integration approaches. PMID:26257437
Defense Science Board Task Force Report on Next-Generation Unmanned Undersea Systems
2016-10-01
active learning occurs in an environment that extends beyondchoreographed demonstrations designed to validate pre -determined hypotheses. Finally, when...4 OPNAV N99 should coordinate a broad-based design , development, and experimental effort to bypass traditional limitations for unmanned undersea...approaches that could facilitate rapid experimentation , operational demonstration of capabilities, and deployment of initial capabilities that show
Radiotherapy using a laser proton accelerator
NASA Astrophysics Data System (ADS)
Murakami, Masao; Hishikawa, Yoshio; Miyajima, Satoshi; Okazaki, Yoshiko; Sutherland, Kenneth L.; Abe, Mitsuyuki; Bulanov, Sergei V.; Daido, Hiroyuki; Esirkepov, Timur Zh.; Koga, James; Yamagiwa, Mitsuru; Tajima, Toshiki
2008-06-01
Laser acceleration promises innovation in particle beam therapy of cancer where an ultra-compact accelerator system for cancer beam therapy can become affordable to a broad range of patients. This is not feasible without the introduction of a technology that is radically different from the conventional accelerator-based approach. Because of its compactness and other novel characteristics, the laser acceleration method provides many enhanced capabilities
Situating and teaching 21st century zoology: revealing pattern in the form and function of animals.
Russell, Anthony P
2009-09-01
The current challenges (increasing levels of integration in the biological sciences) facing the teaching of zoology and the structure of the zoology curriculum are explored herein. General context is provided and a more focused scrutiny of the situation in North America is presented. The changing emphases in more broadly-based biological sciences programs in North America are outlined, and their influence on the role of zoology as part of fundamental biological training is considered. The longer term impact of such changes in emphasis on the teaching of zoology is discussed, and the central role that zoology can play in dealing with both science content and science education is advanced. Based upon a focal workshop on the future of the zoology curriculum in Canada, a perspective on the challenges facing curriculum evolution is provided. Extensive curriculum redesign is called for to ensure that zoology provides a broad-scale integrative approach to the understanding of biodiversity in evolutionary, ecological and functional contexts. Barriers to, and drivers of change are identified and the need for collaborative approaches to curricular evolution is emphasized. © 2009 ISZS, Blackwell Publishing and IOZ/CAS.
Mechanistic explanation, cognitive systems demarcation, and extended cognition.
van Eck, Dingmar; Looren de Jong, Huib
2016-10-01
Approaches to the Internalism-Externalism controversy in the philosophy of mind often involve both (broadly) metaphysical and explanatory considerations. Whereas originally most emphasis seems to have been placed on metaphysical concerns, recently the explanation angle is getting more attention. Explanatory considerations promise to offer more neutral grounds for cognitive systems demarcation than (broadly) metaphysical ones. However, it has been argued that explanation-based approaches are incapable of determining the plausibility of internalist-based conceptions of cognition vis-à-vis externalist ones. On this perspective, improved metaphysics is the route along which to solve the Internalist-Externalist stalemate. In this paper we challenge this claim. Although we agree that explanation-orientated approaches have indeed so far failed to deliver solid means for cognitive system demarcation, we elaborate a more promising explanation-oriented framework to address this issue. We argue that the mutual manipulability account of constitutive relevance in mechanisms, extended with the criterion of 'fat-handedness', is capable of plausibly addressing the cognitive systems demarcation problem, and thus able to decide on the explanatory traction of Internalist vs. Externalist conceptions, on a case-by-case basis. Our analysis also highlights why some other recent mechanistic takes on the problem of cognitive systems demarcation have been unsuccessful. We illustrate our claims with a case on gestures and learning. Copyright © 2016 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Schiering, David W.; Walton, Robert B.; Brown, Christopher W.; Norman, Mark L.; Brewer, Joseph; Scott, James
2004-12-01
IR spectroscopy is a broadly applicable technique for the identification of covalent materials. Recent advances in instrumentation have made Fourier Transform infrared (FT-IR) spectroscopy available for field characterization of suspect materials. Presently, this instrumentation is broadly deployed and used for the identification of potential chemical hazards. This discussion concerns work towards expanding the analytical utility of field-based FT-IR spectrometry in the characterization of biological threats. Two classes of materials were studied: biologically produced chemical toxins which were non-peptide in nature and peptide toxin. The IR spectroscopic identification of aflatoxin-B1, trichothecene T2 mycotoxin, and strychnine was evaluated using the approach of spectral searching against large libraries of materials. For pure components, the IR method discriminated the above toxins at better than the 99% confidence level. The ability to identify non-peptide toxins in mixtures was also evaluated using a "spectral stripping" search approach. For the mixtures evaluated, this method was able to identify the mixture components from ca. 32K spectral library entries. Castor bean extract containing ricin was used as a representative peptide toxin. Due to similarity in protein spectra, a SIMCA pattern recognition methodology was evaluated for classifying peptide toxins. In addition to castor bean extract the method was validated using bovine serum albumin and myoglobin as simulants. The SIMCA approach was successful in correctly classifying these samples at the 95% confidence level.
Predicting Graduation Rates at 4-Year Broad Access Institutions Using a Bayesian Modeling Approach
ERIC Educational Resources Information Center
Crisp, Gloria; Doran, Erin; Salis Reyes, Nicole A.
2018-01-01
This study models graduation rates at 4-year broad access institutions (BAIs). We examine the student body, structural-demographic, and financial characteristics that best predict 6-year graduation rates across two time periods (2008-2009 and 2014-2015). A Bayesian model averaging approach is utilized to account for uncertainty in variable…
Milestones toward Majorana-based quantum computing
NASA Astrophysics Data System (ADS)
Alicea, Jason
Experiments on nanowire-based Majorana platforms now appear poised to move beyond the preliminary problem of zero-mode detection and towards loftier goals of realizing non-Abelian statistics and quantum information applications. Using an approach that synthesizes recent materials growth breakthroughs with tools long successfully deployed in quantum-dot research, I will outline a number of relatively modest milestones that progressively bridge the gap between the current state of the art and these grand longer-term challenges. The intermediate Majorana experiments surveyed in this talk should be broadly adaptable to other approaches as well. Supported by the National Science Foundation (DMR-1341822), Institute for Quantum Information and Matter, and Walter Burke Institute at Caltech.
Broadband and Wide Field-of-view Plasmonic Metasurface-enabled Waveplates
Jiang, Zhi Hao; Lin, Lan; Ma, Ding; Yun, Seokho; Werner, Douglas H.; Liu, Zhiwen; Mayer, Theresa S.
2014-01-01
Quasi two-dimensional metasurfaces composed of subwavelength nanoresonator arrays can dramatically alter the properties of light in an ultra-thin planar geometry, enabling new optical functions such as anomalous reflection and refraction, polarization filtering, and wavefront modulation. However, previous metasurface-based nanostructures suffer from low efficiency, narrow bandwidth and/or limited field-of-view due to their operation near the plasmonic resonance. Here we demonstrate plasmonic metasurface-based nanostructures for high-efficiency, angle-insensitive polarization transformation over a broad octave-spanning bandwidth. The structures are realized by optimizing the anisotropic response of an array of strongly coupled nanorod resonators to tailor the interference of light at the subwavelength scale. Nanofabricated reflective half-wave and quarter-wave plates designed using this approach have measured polarization conversion ratios and reflection magnitudes greater than 92% over a broad wavelength range from 640 to 1290 nm and a wide field-of-view up to ±40°. This work outlines a versatile strategy to create metasurface-based photonics with diverse optical functionalities. PMID:25524830
Prioritizing Genes Related to Nicotine Addiction Via a Multi-source-Based Approach.
Liu, Xinhua; Liu, Meng; Li, Xia; Zhang, Lihua; Fan, Rui; Wang, Ju
2015-08-01
Nicotine has a broad impact on both the central and peripheral nervous systems. Over the past decades, an increasing number of genes potentially involved in nicotine addiction have been identified by different technical approaches. However, the molecular mechanisms underlying nicotine addiction remain largely unknown. Under such situation, prioritizing the candidate genes for further investigation is becoming increasingly important. In this study, we presented a multi-source-based gene prioritization approach for nicotine addiction by utilizing the vast amounts of information generated from for nicotine addiction study during the past years. In this approach, we first collected and curated genes from studies in four categories, i.e., genetic association analysis, genetic linkage analysis, high-throughput gene/protein expression analysis, and literature search of single gene/protein-based studies. Based on these resources, the genes were scored and a weight value was determined for each category. Finally, the genes were ranked by their combined scores, and 220 genes were selected as the prioritized nicotine addiction-related genes. Evaluation suggested the prioritized genes were promising targets for further analysis and replication study.
Broadly tunable thin-film intereference coatings: active thin films for telecom applications
NASA Astrophysics Data System (ADS)
Domash, Lawrence H.; Ma, Eugene Y.; Lourie, Mark T.; Sharfin, Wayne F.; Wagner, Matthias
2003-06-01
Thin film interference coatings (TFIC) are the most widely used optical technology for telecom filtering, but until recently no tunable versions have been known except for mechanically rotated filters. We describe a new approach to broadly tunable TFIC components based on the thermo-optic properties of semiconductor thin films with large thermo-optic coefficients 3.6X10[-4]/K. The technology is based on amorphous silicon thin films deposited by plasma-enhanced chemical vapor deposition (PECVD), a process adapted for telecom applications from its origins in the flat-panel display and solar cell industries. Unlike MEMS devices, tunable TFIC can be designed as sophisticated multi-cavity, multi-layer optical designs. Applications include flat-top passband filters for add-drop multiplexing, tunable dispersion compensators, tunable gain equalizers and variable optical attenuators. Extremely compact tunable devices may be integrated into modules such as optical channel monitors, tunable lasers, gain-equalized amplifiers, and tunable detectors.
LWIR pupil imaging and prospects for background compensation
NASA Astrophysics Data System (ADS)
LeVan, Paul; Sakoglu, Ünal; Stegall, Mark; Pierce, Greg
2015-08-01
A previous paper described LWIR Pupil Imaging with a sensitive, low-flux focal plane array, and behavior of this type of system for higher flux operations as understood at the time. We continue this investigation, and report on a more detailed characterization of the system over a broad range of pixel fluxes. This characterization is then shown to enable non-uniformity correction over the flux range, using a standard approach. Since many commercial tracking platforms include a "guider port" that accepts pulse width modulation (PWM) error signals, we have also investigated a variation on the use of this port to "dither" the tracking platform in synchronization with the continuous collection of infrared images. The resulting capability has a broad range of applications that extend from generating scene motion in the laboratory for quantifying performance of "realtime, scene-based non-uniformity correction" approaches, to effectuating subtraction of bright backgrounds by alternating viewing aspect between a point source and adjacent, source-free backgrounds.
Bryson, Robert W; Jaeger, Jef R; Lemos-Espinal, Julio A; Lazcano, David
2012-09-01
Interpretations of phylogeographic patterns can change when analyses shift from single gene-tree to multilocus coalescent analyses. Using multilocus coalescent approaches, a species tree and divergence times can be estimated from a set of gene trees while accounting for gene-tree stochasticity. We utilized the conceptual strengths of a multilocus coalescent approach coupled with complete range-wide sampling to examine the speciation history of a broadly distributed, North American warm-desert toad, Anaxyrus punctatus. Phylogenetic analyses provided strong support for three major lineages within A. punctatus. Each lineage broadly corresponded to one of three desert regions. Early speciation in A. punctatus appeared linked to late Miocene-Pliocene development of the Baja California peninsula. This event was likely followed by a Pleistocene divergence associated with the separation of the Chihuahuan and Sonoran Deserts. Our multilocus coalescent-based reconstruction provides an informative contrast to previous single gene-tree estimates of the evolutionary history of A. punctatus. Copyright © 2012 Elsevier Inc. All rights reserved.
Advancing Health Literacy Measurement: A Pathway to Better Health and Health System Performance
Pleasant, Andrew
2014-01-01
The concept of health literacy initially emerged and continues to gain strength as an approach to improving health status and the performance of health systems. Numerous studies clearly link low levels of education, literacy, and health literacy with poor health, poor health care utilization, increased barriers to care, and early death. However, theoretical understandings and methods of measuring the complex social construct of health literacy have experienced a continual evolution that remains incomplete. As a result, the seemingly most-cited definition of health literacy proposed in the now-decade-old Institute of Medicine report on health literacy is long overdue for updating. Such an effort should engage a broad and diverse set of health literacy researchers, practitioners, and members of the public in creating a definition that can earn broad consensus through validation testing in a rigorous scientific approach. That effort also could produce the basis for a new universally applicable measure of health literacy. Funders, health systems, and policymakers should reconsider their timid approach to health literacy. Although the field and corresponding evidence base are not perfect, health literacy—especially when combined with a focus on prevention and integrative health—is one of the most promising approaches to advancing public health. PMID:25491583
A Non-parametric Approach to Constrain the Transfer Function in Reverberation Mapping
NASA Astrophysics Data System (ADS)
Li, Yan-Rong; Wang, Jian-Min; Bai, Jin-Ming
2016-11-01
Broad emission lines of active galactic nuclei stem from a spatially extended region (broad-line region, BLR) that is composed of discrete clouds and photoionized by the central ionizing continuum. The temporal behaviors of these emission lines are blurred echoes of continuum variations (I.e., reverberation mapping, RM) and directly reflect the structures and kinematic information of BLRs through the so-called transfer function (also known as the velocity-delay map). Based on the previous works of Rybicki and Press and Zu et al., we develop an extended, non-parametric approach to determine the transfer function for RM data, in which the transfer function is expressed as a sum of a family of relatively displaced Gaussian response functions. Therefore, arbitrary shapes of transfer functions associated with complicated BLR geometry can be seamlessly included, enabling us to relax the presumption of a specified transfer function frequently adopted in previous studies and to let it be determined by observation data. We formulate our approach in a previously well-established framework that incorporates the statistical modeling of continuum variations as a damped random walk process and takes into account long-term secular variations which are irrelevant to RM signals. The application to RM data shows the fidelity of our approach.
Campbell, J Elliott; Moen, Jeremie C; Ney, Richard A; Schnoor, Jerald L
2008-03-01
Estimates of forest soil organic carbon (SOC) have applications in carbon science, soil quality studies, carbon sequestration technologies, and carbon trading. Forest SOC has been modeled using a regression coefficient methodology that applies mean SOC densities (mass/area) to broad forest regions. A higher resolution model is based on an approach that employs a geographic information system (GIS) with soil databases and satellite-derived landcover images. Despite this advancement, the regression approach remains the basis of current state and federal level greenhouse gas inventories. Both approaches are analyzed in detail for Wisconsin forest soils from 1983 to 2001, applying rigorous error-fixing algorithms to soil databases. Resulting SOC stock estimates are 20% larger when determined using the GIS method rather than the regression approach. Average annual rates of increase in SOC stocks are 3.6 and 1.0 million metric tons of carbon per year for the GIS and regression approaches respectively.
Deaths from Pesticide Poisoning: Are we lacking a global response?
Bertolote, JM; Fleischmann, A; Eddleston, M; Gunnell, D
2008-01-01
Self-poisoning with pesticides accounts for around a third of all suicides worldwide. To tackle this problem, WHO announced a Global Public Health initiative in 2005. Planned approaches will range from Government regulatory action to the development of new treatments for pesticide poisoning. With broad-based support this strategy will have a major impact on the global burden of suicide. PMID:16946353
Keeping it wild: Mapping wilderness character in the United States
Steve Carver; James Tricker; Peter Landres
2013-01-01
A GIS-based approach is developed to identify the state of wilderness character in US wilderness areas using Death Valley National Park (DEVA) as a case study. A set of indicators and measures are identified by DEVA staff and used as the basis for developing a flexible and broadly applicable framework to map wilderness character using data inputs selected by park staff...
Kim, Jinhee; Kang, Won-Hee; Hwang, Jeena; Yang, Hee-Bum; Dosun, Kim; Oh, Chang-Sik; Kang, Byoung-Cheorl
2014-08-01
The protein-protein interaction between VPg (viral protein genome-linked) of potyviruses and eIF4E (eukaryotic initiation factor 4E) or eIF(iso)4E of their host plants is a critical step in determining viral virulence. In this study, we evaluated the approach of engineering broad-spectrum resistance in Chinese cabbage (Brassica rapa) to Turnip mosaic virus (TuMV), which is one of the most important potyviruses, by a systematic knowledge-based approach to interrupt the interaction between TuMV VPg and B. rapa eIF(iso)4E. The seven amino acids in the cap-binding pocket of eIF(iso)4E were selected on the basis of other previous results and comparison of protein models of cap-binding pockets, and mutated. Yeast two-hybrid assay and co-immunoprecipitation analysis demonstrated that W95L, K150L and W95L/K150E amino acid mutations of B. rapa eIF(iso)4E interrupted its interaction with TuMV VPg. All eIF(iso)4E mutants were able to complement an eIF4E-knockout yeast strain, indicating that the mutated eIF(iso)4E proteins retained their function as a translational initiation factor. To determine whether these mutations could confer resistance, eIF(iso)4E W95L, W95L/K150E and eIF(iso)4E wild-type were over-expressed in a susceptible Chinese cabbage cultivar. Evaluation of the TuMV resistance of T1 and T2 transformants demonstrated that the over-expression of the eIF(iso)4E mutant forms can confer resistance to multiple TuMV strains. These data demonstrate the utility of knowledge-based approaches for the engineering of broad-spectrum resistance in Chinese cabbage. © 2014 BSPP AND JOHN WILEY & SONS LTD.
Atilola, Olayinka
2014-01-01
Efforts at improving child-health and development initiatives in sub-Saharan Africa had focused on the physical health of children due to the neglect of child and adolescent mental health (CAMH) policy initiatives. A thorough and broad-based understanding of the prevalent child mental-health risk and vulnerability factors is needed to successfully articulate CAMH policies. In this discourse, we present a narrative on the child mental-health risk and vulnerability factors in sub-Saharan Africa. Through an ecological point of view, we identified widespread family poverty, poor availability and uptake of childcare resources, inadequate community and institutional childcare systems, and inadequate framework for social protection for vulnerable children as among the risk and vulnerability factors for CAMH in the region. Others are poor workplace policy/practice that does not support work-family life balance, poor legislative framework for child protection, and some harmful traditional practices. We conclude that an ecological approach shows that child mental-health risks are diverse and cut across different layers of the care environment. The approach also provides a broad and holistic template from which appropriate CAMH policy direction in sub-Saharan Africa can be understood. PMID:24834431
Atilola, Olayinka
2014-01-01
Efforts at improving child-health and development initiatives in sub-Saharan Africa had focused on the physical health of children due to the neglect of child and adolescent mental health (CAMH) policy initiatives. A thorough and broad-based understanding of the prevalent child mental-health risk and vulnerability factors is needed to successfully articulate CAMH policies. In this discourse, we present a narrative on the child mental-health risk and vulnerability factors in sub-Saharan Africa. Through an ecological point of view, we identified widespread family poverty, poor availability and uptake of childcare resources, inadequate community and institutional childcare systems, and inadequate framework for social protection for vulnerable children as among the risk and vulnerability factors for CAMH in the region. Others are poor workplace policy/practice that does not support work-family life balance, poor legislative framework for child protection, and some harmful traditional practices. We conclude that an ecological approach shows that child mental-health risks are diverse and cut across different layers of the care environment. The approach also provides a broad and holistic template from which appropriate CAMH policy direction in sub-Saharan Africa can be understood.
Tharakaraman, Kannan; Robinson, Luke N.; Hatas, Andrew; Chen, Yi-Ling; Siyue, Liu; Raguram, S.; Sasisekharan, V.; Wogan, Gerald N.; Sasisekharan, Ram
2013-01-01
Affinity improvement of proteins, including antibodies, by computational chemistry broadly relies on physics-based energy functions coupled with refinement. However, achieving significant enhancement of binding affinity (>10-fold) remains a challenging exercise, particularly for cross-reactive antibodies. We describe here an empirical approach that captures key physicochemical features common to antigen–antibody interfaces to predict protein–protein interaction and mutations that confer increased affinity. We apply this approach to the design of affinity-enhancing mutations in 4E11, a potent cross-reactive neutralizing antibody to dengue virus (DV), without a crystal structure. Combination of predicted mutations led to a 450-fold improvement in affinity to serotype 4 of DV while preserving, or modestly increasing, affinity to serotypes 1–3 of DV. We show that increased affinity resulted in strong in vitro neutralizing activity to all four serotypes, and that the redesigned antibody has potent antiviral activity in a mouse model of DV challenge. Our findings demonstrate an empirical computational chemistry approach for improving protein–protein docking and engineering antibody affinity, which will help accelerate the development of clinically relevant antibodies. PMID:23569282
Agishev, Ravil; Comerón, Adolfo; Rodriguez, Alejandro; Sicard, Michaël
2014-05-20
In this paper, we show a renewed approach to the generalized methodology for atmospheric lidar assessment, which uses the dimensionless parameterization as a core component. It is based on a series of our previous works where the problem of universal parameterization over many lidar technologies were described and analyzed from different points of view. The modernized dimensionless parameterization concept applied to relatively new silicon photomultiplier detectors (SiPMs) and traditional photomultiplier (PMT) detectors for remote-sensing instruments allowed predicting the lidar receiver performance with sky background available. The renewed approach can be widely used to evaluate a broad range of lidar system capabilities for a variety of lidar remote-sensing applications as well as to serve as a basis for selection of appropriate lidar system parameters for a specific application. Such a modernized methodology provides a generalized, uniform, and objective approach for evaluation of a broad range of lidar types and systems (aerosol, Raman, DIAL) operating on different targets (backscatter or topographic) and under intense sky background conditions. It can be used within the lidar community to compare different lidar instruments.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Yan-Rong; Wang, Jian-Min; Bai, Jin-Ming, E-mail: liyanrong@mail.ihep.ac.cn
Broad emission lines of active galactic nuclei stem from a spatially extended region (broad-line region, BLR) that is composed of discrete clouds and photoionized by the central ionizing continuum. The temporal behaviors of these emission lines are blurred echoes of continuum variations (i.e., reverberation mapping, RM) and directly reflect the structures and kinematic information of BLRs through the so-called transfer function (also known as the velocity-delay map). Based on the previous works of Rybicki and Press and Zu et al., we develop an extended, non-parametric approach to determine the transfer function for RM data, in which the transfer function ismore » expressed as a sum of a family of relatively displaced Gaussian response functions. Therefore, arbitrary shapes of transfer functions associated with complicated BLR geometry can be seamlessly included, enabling us to relax the presumption of a specified transfer function frequently adopted in previous studies and to let it be determined by observation data. We formulate our approach in a previously well-established framework that incorporates the statistical modeling of continuum variations as a damped random walk process and takes into account long-term secular variations which are irrelevant to RM signals. The application to RM data shows the fidelity of our approach.« less
Therapies in inborn errors of oxidative metabolism
Schiff, Manuel; Bénit, Paule; Jacobs, Howard T.; Vockley, Jerry; Rustin, Pierre
2014-01-01
Mitochondrial diseases encompass a wide range of presentations and mechanisms, dictating a need to consider both broad-based and disease-specific therapies. The manifestations of mitochondrial dysfunction and the response to therapy vary between individuals. This probably reflects the genetic complexity of mitochondrial biology, which requires an excess of 2000 genes for proper function, with numerous interfering epigenetic and environmental factors. Accordingly, we are increasingly aware of the complexity of these diseases which involve far more than merely decreased ATP supply. Indeed, recent therapeutic progress has addressed only specific disease entities. In this review present and prospective therapeutic approaches will be discussed on the basis of targets and mechanism of action, but with a broad outlook on their potential applications. PMID:22633959
Broad Ligament Haematoma Following Normal Vaginal Delivery.
Ibrar, Faiza; Awan, Azra Saeed; Fatima, Touseef; Tabassum, Hina
2017-01-01
A 37-year-old, patient presented in emergency with history of normal vaginal delivery followed by development of abdominal distention, vomiting, constipation for last 3 days. She was para 4 and had normal vaginal delivery by traditional birth attendant at peripheral hospital 3 days back. Imaging study revealed a heterogeneous complex mass, ascites, pleural effusion, air fluid levels with dilatation gut loops. Based upon pelvic examination by senior gynaecologist in combination with ultrasound; a clinical diagnosis of broad ligament haematoma was made. However, vomiting and abdominal distention raised suspicion of intestinal obstruction. Due to worsening abdominal distention exploratory laparotomy was carried out. It was pseudo colonic obstruction and caecostomy was done. Timely intervention by multidisciplinary approach saved patient life with minimal morbidity.
Analysis of population inquiry on practices for ultraviolet radiation protection.
Celaj, Stela; Deng, Jie; Murphy, Brendan L
2017-10-15
UV radiation exposure is one of the key modifiable risk factors for skin cancer. Hence, patient education regarding skin protection and sunscreen use is of tremendous importance to public health. To better understand patient practices regarding skin protection in a population level, we looked into the Internet search behavior of the US-based population. We investigated patient inquires on the United States Food and Drug Administration (FDA) announcements regarding sunscreen use by quantifying search terms such as "broad spectrum sunscreen", "sunscreen" and "sunblock" with Google Trends, a novel methodology for understanding internet search practices. Our findings show that "broad spectrum sunscreen" searches were significantly increased post 2011 FDA announcements, which suggest increased public awareness regarding the importance of broad spectrum protection. It is encouraging these preliminary results indicate that skin protection practices are being increasingly investigated by the general public and may serve as a novel approach for identifying areas of improvement regarding patient education on the reduction of the risk for skin cancer.
Hao, Jie; Gao, Yuxia; Li, Ying; Yan, Qiang; Hu, Jun; Ju, Yong
2017-09-05
Thermoresponsive water-soluble polymers are of great importance since they typically show a lower critical solution temperature (LCST) in aqueous media. In this research, the LCST change in broad temperature ranges of copolymers composed of natural glycyrrhetinic acid (GA)-based methacrylate and N,N'-dimethylacrylamides (DMAs) was investigated as a function of the concentration and the content of GA pendants. By complexation of GA pendants with β-cyclodextrin (β-CD), a side-chain polypseudorotaxane was obtained, which exhibited a significant increase in the LCST of copolymers. Moreover, the precisely reversible control of the LCST behavior was realized through adding a competing guest molecule, sodium 1-admantylcarboxylate. This work illustrates a simple and effective approach to endow water-soluble polymers with broad temperature tunability and helps us further understand the effect of a biocompatible host-guest complementary β-CD/GA pair on the thermoresponsive process. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Development of potent in vivo mutagenesis plasmids with broad mutational spectra
Badran, Ahmed H.; Liu, David R.
2015-01-01
Methods to enhance random mutagenesis in cells offer advantages over in vitro mutagenesis, but current in vivo methods suffer from a lack of control, genomic instability, low efficiency and narrow mutational spectra. Using a mechanism-driven approach, we created a potent, inducible, broad-spectrum and vector-based mutagenesis system in E. coli that enhances mutation 322,000-fold over basal levels, surpassing the mutational efficiency and spectra of widely used in vivo and in vitro methods. We demonstrate that this system can be used to evolve antibiotic resistance in wild-type E. coli in <24 h, outperforming chemical mutagens, ultraviolet light and the mutator strain XL1-Red under similar conditions. This system also enables the continuous evolution of T7 RNA polymerase variants capable of initiating transcription using the T3 promoter in <10 h. Our findings enable broad-spectrum mutagenesis of chromosomes, episomes and viruses in vivo, and are applicable to both bacterial and bacteriophage-mediated laboratory evolution platforms. PMID:26443021
Development of potent in vivo mutagenesis plasmids with broad mutational spectra.
Badran, Ahmed H; Liu, David R
2015-10-07
Methods to enhance random mutagenesis in cells offer advantages over in vitro mutagenesis, but current in vivo methods suffer from a lack of control, genomic instability, low efficiency and narrow mutational spectra. Using a mechanism-driven approach, we created a potent, inducible, broad-spectrum and vector-based mutagenesis system in E. coli that enhances mutation 322,000-fold over basal levels, surpassing the mutational efficiency and spectra of widely used in vivo and in vitro methods. We demonstrate that this system can be used to evolve antibiotic resistance in wild-type E. coli in <24 h, outperforming chemical mutagens, ultraviolet light and the mutator strain XL1-Red under similar conditions. This system also enables the continuous evolution of T7 RNA polymerase variants capable of initiating transcription using the T3 promoter in <10 h. Our findings enable broad-spectrum mutagenesis of chromosomes, episomes and viruses in vivo, and are applicable to both bacterial and bacteriophage-mediated laboratory evolution platforms.
Application of a Sensemaking Approach to Ethics Training in the Physical Sciences and Engineering
NASA Astrophysics Data System (ADS)
Kligyte, Vykinta; Marcy, Richard T.; Waples, Ethan P.; Sevier, Sydney T.; Godfrey, Elaine S.; Mumford, Michael D.; Hougen, Dean F.
2008-06-01
Integrity is a critical determinant of the effectiveness of research organizations in terms of producing high quality research and educating the new generation of scientists. A number of responsible conduct of research (RCR) training programs have been developed to address this growing organizational concern. However, in spite of a significant body of research in ethics training, it is still unknown which approach has the highest potential to enhance researchers' integrity. One of the approaches showing some promise in improving researchers' integrity has focused on the development of ethical decision-making skills. The current effort proposes a novel curriculum that focuses on broad metacognitive reasoning strategies researchers use when making sense of day-to-day social and professional practices that have ethical implications for the physical sciences and engineering. This sensemaking training has been implemented in a professional sample of scientists conducting research in electrical engineering, atmospheric and computer sciences at a large multi-cultural, multi-disciplinary, and multi-university research center. A pre-post design was used to assess training effectiveness using scenario-based ethical decision-making measures. The training resulted in enhanced ethical decision-making of researchers in relation to four ethical conduct areas, namely data management, study conduct, professional practices, and business practices. In addition, sensemaking training led to researchers' preference for decisions involving the application of the broad metacognitive reasoning strategies. Individual trainee and training characteristics were used to explain the study findings. Broad implications of the findings for ethics training development, implementation, and evaluation in the sciences are discussed.
Application of a sensemaking approach to ethics training in the physical sciences and engineering.
Kligyte, Vykinta; Marcy, Richard T; Waples, Ethan P; Sevier, Sydney T; Godfrey, Elaine S; Mumford, Michael D; Hougen, Dean F
2008-06-01
Integrity is a critical determinant of the effectiveness of research organizations in terms of producing high quality research and educating the new generation of scientists. A number of responsible conduct of research (RCR) training programs have been developed to address this growing organizational concern. However, in spite of a significant body of research in ethics training, it is still unknown which approach has the highest potential to enhance researchers' integrity. One of the approaches showing some promise in improving researchers' integrity has focused on the development of ethical decision-making skills. The current effort proposes a novel curriculum that focuses on broad metacognitive reasoning strategies researchers use when making sense of day-to-day social and professional practices that have ethical implications for the physical sciences and engineering. This sensemaking training has been implemented in a professional sample of scientists conducting research in electrical engineering, atmospheric and computer sciences at a large multi-cultural, multi-disciplinary, and multi-university research center. A pre-post design was used to assess training effectiveness using scenario-based ethical decision-making measures. The training resulted in enhanced ethical decision-making of researchers in relation to four ethical conduct areas, namely data management, study conduct, professional practices, and business practices. In addition, sensemaking training led to researchers' preference for decisions involving the application of the broad metacognitive reasoning strategies. Individual trainee and training characteristics were used to explain the study findings. Broad implications of the findings for ethics training development, implementation, and evaluation in the sciences are discussed.
Assessing Eli Broad's Assault on Public School System Leadership
ERIC Educational Resources Information Center
English, Fenwick W.; Crowder, Zan
2012-01-01
Eli Broad's approach to reforming urban public education does not recognize his own self-interest in promoting changes within such educational systems, a classic problem of misrecognition. The Broad agenda is an assault on the notion of the mission of public education as a service instead of a for-profit enterprise concerned with making money for…
USGS perspectives on an integrated approach to watershed and coastal management
Larsen, Matthew C.; Hamilton, Pixie A.; Haines, John W.; Mason, Jr., Robert R.
2010-01-01
The writers discuss three critically important steps necessary for achieving the goal for improved integrated approaches on watershed and coastal protection and management. These steps involve modernization of monitoring networks, creation of common data and web services infrastructures, and development of modeling, assessment, and research tools. Long-term monitoring is needed for tracking the effectiveness approaches for controlling land-based sources of nutrients, contaminants, and invasive species. The integration of mapping and monitoring with conceptual and mathematical models, and multidisciplinary assessments is important in making well-informed decisions. Moreover, a better integrated data network is essential for mapping, statistical, and modeling applications, and timely dissemination of data and information products to a broad community of users.
Di Mario, Giuseppina; Soprana, Elisa; Gubinelli, Francesco; Panigada, Maddalena; Facchini, Marzia; Fabiani, Concetta; Garulli, Bruno; Basileo, Michela; Cassone, Antonio; Siccardi, Antonio; Donatelli, Isabella; Castrucci, Maria R
2017-03-01
Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses. Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus. Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge. Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for a universal influenza vaccine.
Reavley, Nicola; Livingston, Jenni; Buchbinder, Rachelle; Bennell, Kim; Stecki, Chris; Osborne, Richard Harry
2010-02-01
Despite demands for evidence-based research and practice, little attention has been given to systematic approaches to the development of complex interventions to tackle workplace health problems. This paper outlines an approach to the initial stages of a workplace program development which integrates health promotion and disease management. The approach commences with systematic and genuine processes of obtaining information from key stakeholders with broad experience of these interventions. This information is constructed into a program framework in which practice-based and research-informed elements are both valued. We used this approach to develop a workplace education program to reduce the onset and impact of a common chronic disease - osteoarthritis. To gain information systematically at a national level, a structured concept mapping workshop with 47 participants from across Australia was undertaken. Participants were selected to maximise the whole-of-workplace perspective and included health education providers, academics, clinicians and policymakers. Participants generated statements in response to a seeding statement: Thinking as broadly as possible, what changes in education and support should occur in the workplace to help in the prevention and management of arthritis? Participants grouped the resulting statements into conceptually coherent groups and a computer program was used to generate a 'cluster map' along with a list of statements sorted according to cluster membership. In combination with research-based evidence, the concept map informed the development of a program logic model incorporating the program's guiding principles, possible service providers, services, training modes, program elements and the causal processes by which participants might benefit. The program logic model components were further validated through research findings from diverse fields, including health education, coaching, organisational learning, workplace interventions, workforce development and osteoarthritis disability prevention. In summary, wide and genuine consultation, concept mapping, and evidence-based program logic development were integrated to develop a whole-of-system complex intervention in which potential effectiveness and assimilation into the workplace for which optimised. Copyright 2009 Elsevier Ltd. All rights reserved.
Computational neuropharmacology: dynamical approaches in drug discovery.
Aradi, Ildiko; Erdi, Péter
2006-05-01
Computational approaches that adopt dynamical models are widely accepted in basic and clinical neuroscience research as indispensable tools with which to understand normal and pathological neuronal mechanisms. Although computer-aided techniques have been used in pharmaceutical research (e.g. in structure- and ligand-based drug design), the power of dynamical models has not yet been exploited in drug discovery. We suggest that dynamical system theory and computational neuroscience--integrated with well-established, conventional molecular and electrophysiological methods--offer a broad perspective in drug discovery and in the search for novel targets and strategies for the treatment of neurological and psychiatric diseases.
Video Denoising via Dynamic Video Layering
NASA Astrophysics Data System (ADS)
Guo, Han; Vaswani, Namrata
2018-07-01
Video denoising refers to the problem of removing "noise" from a video sequence. Here the term "noise" is used in a broad sense to refer to any corruption or outlier or interference that is not the quantity of interest. In this work, we develop a novel approach to video denoising that is based on the idea that many noisy or corrupted videos can be split into three parts - the "low-rank layer", the "sparse layer", and a small residual (which is small and bounded). We show, using extensive experiments, that our denoising approach outperforms the state-of-the-art denoising algorithms.
Riniker, Sereina; Fechner, Nikolas; Landrum, Gregory A
2013-11-25
The concept of data fusion - the combination of information from different sources describing the same object with the expectation to generate a more accurate representation - has found application in a very broad range of disciplines. In the context of ligand-based virtual screening (VS), data fusion has been applied to combine knowledge from either different active molecules or different fingerprints to improve similarity search performance. Machine-learning (ML) methods based on fusion of multiple homogeneous classifiers, in particular random forests, have also been widely applied in the ML literature. The heterogeneous version of classifier fusion - fusing the predictions from different model types - has been less explored. Here, we investigate heterogeneous classifier fusion for ligand-based VS using three different ML methods, RF, naïve Bayes (NB), and logistic regression (LR), with four 2D fingerprints, atom pairs, topological torsions, RDKit fingerprint, and circular fingerprint. The methods are compared using a previously developed benchmarking platform for 2D fingerprints which is extended to ML methods in this article. The original data sets are filtered for difficulty, and a new set of challenging data sets from ChEMBL is added. Data sets were also generated for a second use case: starting from a small set of related actives instead of diverse actives. The final fused model consistently outperforms the other approaches across the broad variety of targets studied, indicating that heterogeneous classifier fusion is a very promising approach for ligand-based VS. The new data sets together with the adapted source code for ML methods are provided in the Supporting Information .
NASA Astrophysics Data System (ADS)
Nanda, Tarun; Kumar, B. Ravi; Singh, Vishal
2017-11-01
Micromechanical modeling is used to predict material's tensile flow curve behavior based on microstructural characteristics. This research develops a simplified micromechanical modeling approach for predicting flow curve behavior of dual-phase steels. The existing literature reports on two broad approaches for determining tensile flow curve of these steels. The modeling approach developed in this work attempts to overcome specific limitations of the existing two approaches. This approach combines dislocation-based strain-hardening method with rule of mixtures. In the first step of modeling, `dislocation-based strain-hardening method' was employed to predict tensile behavior of individual phases of ferrite and martensite. In the second step, the individual flow curves were combined using `rule of mixtures,' to obtain the composite dual-phase flow behavior. To check accuracy of proposed model, four distinct dual-phase microstructures comprising of different ferrite grain size, martensite fraction, and carbon content in martensite were processed by annealing experiments. The true stress-strain curves for various microstructures were predicted with the newly developed micromechanical model. The results of micromechanical model matched closely with those of actual tensile tests. Thus, this micromechanical modeling approach can be used to predict and optimize the tensile flow behavior of dual-phase steels.
Integration of heterogeneous data for classification in hyperspectral satellite imagery
NASA Astrophysics Data System (ADS)
Benedetto, J.; Czaja, W.; Dobrosotskaya, J.; Doster, T.; Duke, K.; Gillis, D.
2012-06-01
As new remote sensing modalities emerge, it becomes increasingly important to nd more suitable algorithms for fusion and integration of dierent data types for the purposes of target/anomaly detection and classication. Typical techniques that deal with this problem are based on performing detection/classication/segmentation separately in chosen modalities, and then integrating the resulting outcomes into a more complete picture. In this paper we provide a broad analysis of a new approach, based on creating fused representations of the multi- modal data, which then can be subjected to analysis by means of the state-of-the-art classiers or detectors. In this scenario we shall consider the hyperspectral imagery combined with spatial information. Our approach involves machine learning techniques based on analysis of joint data-dependent graphs and their associated diusion kernels. Then, the signicant eigenvectors of the derived fused graph Laplace operator form the new representation, which provides integrated features from the heterogeneous input data. We compare these fused approaches with analysis of integrated outputs of spatial and spectral graph methods.
Valentine-Maher, Sarah K; Van Dyk, Elizabeth J; Aktan, Nadine M; Bliss, Julie Beshore
2014-03-01
Nursing programs are challenged to prepare future nurses to provide care and affect determinants of health for individuals and populations. This article advances a pedagogical model for clinical education that builds concepts related to both population-level care and direct care in the community through a contextual learning approach. Because the conceptual pillars and hybrid constructivist approach allow for conceptual learning consistency across experiences, the model expands programmatic capacity to use diverse community clinical sites that accept only small numbers of students. The concept-based and hybrid constructivist learning approach is expected to contribute to the development of broad intellectual skills and lifelong learning. The pillar concepts include determinants of health and nursing care of population aggregates; direct care, based on evidence and best practices; appreciation of lived experience of health and illness; public health nursing roles and relationship to ethical and professional formation; and multidisciplinary collaboration. Copyright 2014, SLACK Incorporated.
NASA Astrophysics Data System (ADS)
Ouerhani, Y.; Alfalou, A.; Desthieux, M.; Brosseau, C.
2017-02-01
We present a three-step approach based on the commercial VIAPIX® module for road traffic sign recognition and identification. Firstly, detection in a scene of all objects having characteristics of traffic signs is performed. This is followed by a first-level recognition based on correlation which consists in making a comparison between each detected object with a set of reference images of a database. Finally, a second level of identification allows us to confirm or correct the previous identification. In this study, we perform a correlation-based analysis by combining and adapting the Vander Lugt correlator with the nonlinear joint transformation correlator (JTC). Of particular significance, this approach permits to make a reliable decision on road traffic sign identification. We further discuss a robust scheme allowing us to track a detected road traffic sign in a video sequence for the purpose of increasing the decision performance of our system. This approach can have broad practical applications in the maintenance and rehabilitation of transportation infrastructure, or for drive assistance.
A strategy for developing a launch vehicle system for orbit insertion: Methodological aspects
NASA Astrophysics Data System (ADS)
Klyushnikov, V. Yu.; Kuznetsov, I. I.; Osadchenko, A. S.
2014-12-01
The article addresses methodological aspects of a development strategy to design a launch vehicle system for orbit insertion. The development and implementation of the strategy are broadly outlined. An analysis is provided of the criterial base and input data needed to define the main requirements for the launch vehicle system. Approaches are suggested for solving individual problems in working out the launch vehicle system development strategy.
Trouble with diffusion: Reassessing hillslope erosion laws with a particle-based model
NASA Astrophysics Data System (ADS)
Tucker, Gregory E.; Bradley, D. Nathan
2010-03-01
Many geomorphic systems involve a broad distribution of grain motion length scales, ranging from a few particle diameters to the length of an entire hillslope or stream. Studies of analogous physical systems have revealed that such broad motion distributions can have a significant impact on macroscale dynamics and can violate the assumptions behind standard, local gradient flux laws. Here, a simple particle-based model of sediment transport on a hillslope is used to study the relationship between grain motion statistics and macroscopic landform evolution. Surface grains are dislodged by random disturbance events with probabilities and distances that depend on local microtopography. Despite its simplicity, the particle model reproduces a surprisingly broad range of slope forms, including asymmetric degrading scarps and cinder cone profiles. At low slope angles the dynamics are diffusion like, with a short-range, thin-tailed hop length distribution, a parabolic, convex upward equilibrium slope form, and a linear relationship between transport rate and gradient. As slope angle steepens, the characteristic grain motion length scale begins to approach the length of the slope, leading to planar equilibrium forms that show a strongly nonlinear correlation between transport rate and gradient. These high-probability, long-distance motions violate the locality assumption embedded in many common gradient-based geomorphic transport laws. The example of a degrading scarp illustrates the potential for grain motion dynamics to vary in space and time as topography evolves. This characteristic renders models based on independent, stationary statistics inapplicable. An accompanying analytical framework based on treating grain motion as a survival process is briefly outlined.
Mee, Jonathan A; Bernatchez, Louis; Reist, Jim D; Rogers, Sean M; Taylor, Eric B
2015-01-01
The concept of the designatable unit (DU) affords a practical approach to identifying diversity below the species level for conservation prioritization. However, its suitability for defining conservation units in ecologically diverse, geographically widespread and taxonomically challenging species complexes has not been broadly evaluated. The lake whitefish species complex (Coregonus spp.) is geographically widespread in the Northern Hemisphere, and it contains a great deal of variability in ecology and evolutionary legacy within and among populations, as well as a great deal of taxonomic ambiguity. Here, we employ a set of hierarchical criteria to identify DUs within the Canadian distribution of the lake whitefish species complex. We identified 36 DUs based on (i) reproductive isolation, (ii) phylogeographic groupings, (iii) local adaptation and (iv) biogeographic regions. The identification of DUs is required for clear discussion regarding the conservation prioritization of lake whitefish populations. We suggest conservation priorities among lake whitefish DUs based on biological consequences of extinction, risk of extinction and distinctiveness. Our results exemplify the need for extensive genetic and biogeographic analyses for any species with broad geographic distributions and the need for detailed evaluation of evolutionary history and adaptive ecological divergence when defining intraspecific conservation units. PMID:26029257
Systematic design of broadband path-coiling acoustic metamaterials
NASA Astrophysics Data System (ADS)
Jia, Zhetao; Li, Junfei; Shen, Chen; Xie, Yangbo; Cummer, Steven A.
2018-01-01
A design approach for acoustic metamaterial unit cells based on a coiled path with impedance matching layers (IMLs) is proposed in this paper. A theoretical approach is developed to calculate the transmission of the labyrinthine unit cells with different effective refractive indices. The IML is introduced to broaden the transmission bandwidth and produce a lower envelope boundary of transmission for unit cells of different effective refractive indices. According to the theory, cells of all effective refractive indices can be built to achieve unitary transmission at center working frequencies. The working frequency can be tuned by adjusting the length of the IML. Numerical simulations based on finite element analysis are used to validate the theoretical predictions. The high transmission and low dispersive index nature of our designs are further verified by experiments within a broad frequency band of over 1.4 kHz centered at 2.86 kHz. Our design approach can be useful in various wavefront engineering applications.
Combinatorial and high-throughput screening of materials libraries: review of state of the art.
Potyrailo, Radislav; Rajan, Krishna; Stoewe, Klaus; Takeuchi, Ichiro; Chisholm, Bret; Lam, Hubert
2011-11-14
Rational materials design based on prior knowledge is attractive because it promises to avoid time-consuming synthesis and testing of numerous materials candidates. However with the increase of complexity of materials, the scientific ability for the rational materials design becomes progressively limited. As a result of this complexity, combinatorial and high-throughput (CHT) experimentation in materials science has been recognized as a new scientific approach to generate new knowledge. This review demonstrates the broad applicability of CHT experimentation technologies in discovery and optimization of new materials. We discuss general principles of CHT materials screening, followed by the detailed discussion of high-throughput materials characterization approaches, advances in data analysis/mining, and new materials developments facilitated by CHT experimentation. We critically analyze results of materials development in the areas most impacted by the CHT approaches, such as catalysis, electronic and functional materials, polymer-based industrial coatings, sensing materials, and biomaterials.
Reference dosimetry of proton pencil beams based on dose-area product: a proof of concept.
Gomà, Carles; Safai, Sairos; Vörös, Sándor
2017-06-21
This paper describes a novel approach to the reference dosimetry of proton pencil beams based on dose-area product ([Formula: see text]). It depicts the calibration of a large-diameter plane-parallel ionization chamber in terms of dose-area product in a 60 Co beam, the Monte Carlo calculation of beam quality correction factors-in terms of dose-area product-in proton beams, the Monte Carlo calculation of nuclear halo correction factors, and the experimental determination of [Formula: see text] of a single proton pencil beam. This new approach to reference dosimetry proves to be feasible, as it yields [Formula: see text] values in agreement with the standard and well-established approach of determining the absorbed dose to water at the centre of a broad homogeneous field generated by the superposition of regularly-spaced proton pencil beams.
Molecular basis of glyphosate resistance: Different approaches through protein engineering
Pollegioni, Loredano; Schonbrunn, Ernst; Siehl, Daniel
2011-01-01
Glyphosate (N-phosphonomethyl-glycine) is the most-used herbicide in the world: glyphosate-based formulations exhibit broad-spectrum herbicidal activity with minimal human and environmental toxicity. The extraordinary success of this simple small molecule is mainly due to the high specificity of glyphosate towards the plant enzyme enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway leading to biosynthesis of aromatic amino acids. Starting in 1996, transgenic glyphosate-resistant plants were introduced thus allowing the application of the herbicide to the crop (post-emergence) to remove emerged weeds without crop damage. This review focuses on the evolution of mechanisms of resistance to glyphosate as obtained through natural diversity, the gene shuffling approach to molecular evolution, and a rational, structure-based approach to protein engineering. In addition, we offer rationale for the means by which the modifications made have had their intended effect. PMID:21668647
NASA Astrophysics Data System (ADS)
Rodrigues, João Fabrício Mota; Coelho, Marco Túlio Pacheco; Ribeiro, Bruno R.
2018-04-01
Species distribution models (SDM) have been broadly used in ecology to address theoretical and practical problems. Currently, there are two main approaches to generate SDMs: (i) correlative, which is based on species occurrences and environmental predictor layers and (ii) process-based models, which are constructed based on species' functional traits and physiological tolerances. The distributions estimated by each approach are based on different components of species niche. Predictions of correlative models approach species realized niches, while predictions of process-based are more akin to species fundamental niche. Here, we integrated the predictions of fundamental and realized distributions of the freshwater turtle Trachemys dorbigni. Fundamental distribution was estimated using data of T. dorbigni's egg incubation temperature, and realized distribution was estimated using species occurrence records. Both types of distributions were estimated using the same regression approaches (logistic regression and support vector machines), both considering macroclimatic and microclimatic temperatures. The realized distribution of T. dorbigni was generally nested in its fundamental distribution reinforcing theoretical assumptions that the species' realized niche is a subset of its fundamental niche. Both modelling algorithms produced similar results but microtemperature generated better results than macrotemperature for the incubation model. Finally, our results reinforce the conclusion that species realized distributions are constrained by other factors other than just thermal tolerances.
Ecosystem Based Management in Transition: From Ocean Policy to Application
NASA Astrophysics Data System (ADS)
Saumweber, W. J.; Goldman, E.
2016-02-01
Ecosystem-based management (EBM) has been proposed as a means to improve resource management and stewardship for more than two decades. Over this history, its exact goals and approaches have evolved in concert with advances in science and policy, including a greater understanding of ecosystem function, valuation, and thresholds for change, along with direct reference to EBM principles in statute, regulation, and other Executive Actions. Most recently, and explicitly, the Administration's National Ocean Policy (NOP) called for the development of a Federal EBM framework that would outline principles and guidelines for implementing EBM under existing authorities. This cross-agency framework has yet to be developed, but, the NOP, and related Administration initiatives, have resulted in the practical application of EBM principles in several issue-specific policy initiatives ranging from fisheries and marine protected area management to coastal adaptation and water resource infrastructure investment. In each case, the application of EBM principles uses apparently unique policy mechanisms (e.g. marine planning, ecosystem services assessment, adaptive management, dynamic ocean management, etc.). Despite differences in terminology and policy context, each of these policy initiatives is linked at its core to concepts of integrated and adaptive management that consider broad ecosystem function and services. This practical history of EBM implementation speaks to both the challenges and opportunities in broad incorporation of EBM across diverse policy initiatives and frameworks. We suggest that the continued growth of EBM as a practical policy concept will require a move away from broad frameworks, and towards the identification of specific resource management issues and accompanying policy levers with which to address those issues. In order to promote this progression, Federal policy should recognize and articulate the diverse set of policy mechanisms encompassed under the rubric of EBM and seek to require similar approaches across the spectra of resource management issues.
Ecosystem Based Management in Transition: From Ocean Policy to Application
NASA Astrophysics Data System (ADS)
Saumweber, W. J.; Goldman, E.
2016-12-01
Ecosystem-based management (EBM) has been proposed as a means to improve resource management and stewardship for more than two decades. Over this history, its exact goals and approaches have evolved in concert with advances in science and policy, including a greater understanding of ecosystem function, valuation, and thresholds for change, along with direct reference to EBM principles in statute, regulation, and other Executive Actions. Most recently, and explicitly, the Administration's National Ocean Policy (NOP) called for the development of a Federal EBM framework that would outline principles and guidelines for implementing EBM under existing authorities. This cross-agency framework has yet to be developed, but, the NOP, and related Administration initiatives, have resulted in the practical application of EBM principles in several issue-specific policy initiatives ranging from fisheries and marine protected area management to coastal adaptation and water resource infrastructure investment. In each case, the application of EBM principles uses apparently unique policy mechanisms (e.g. marine planning, ecosystem services assessment, adaptive management, dynamic ocean management, etc.). Despite differences in terminology and policy context, each of these policy initiatives is linked at its core to concepts of integrated and adaptive management that consider broad ecosystem function and services. This practical history of EBM implementation speaks to both the challenges and opportunities in broad incorporation of EBM across diverse policy initiatives and frameworks. We suggest that the continued growth of EBM as a practical policy concept will require a move away from broad frameworks, and towards the identification of specific resource management issues and accompanying policy levers with which to address those issues. In order to promote this progression, Federal policy should recognize and articulate the diverse set of policy mechanisms encompassed under the rubric of EBM and seek to require similar approaches across the spectra of resource management issues.
Carter, Donald M.; Darby, Christopher A.; Lefoley, Bradford C.; Crevar, Corey J.; Alefantis, Timothy; Oomen, Raymond; Anderson, Stephen F.; Strugnell, Tod; Cortés-Garcia, Guadalupe; Vogel, Thorsten U.; Parrington, Mark; Kleanthous, Harold
2016-01-01
ABSTRACT One of the challenges of developing influenza A vaccines is the diversity of antigenically distinct isolates. Previously, a novel hemagglutinin (HA) for H5N1 influenza was derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA elicited a broad antibody response against H5N1 isolates from different clades. We now report the development and characterization of a COBRA-based vaccine for both seasonal and pandemic H1N1 influenza virus isolates. Nine prototype H1N1 COBRA HA proteins were developed and tested in mice using a virus-like particle (VLP) format for the elicitation of broadly reactive, functional antibody responses and protection against viral challenge. These candidates were designed to recognize H1N1 viruses isolated within the last 30 years. In addition, several COBRA candidates were designed based on sequences of H1N1 viruses spanning the past 100 years, including modern pandemic H1N1 isolates. Four of the 9 H1N1 COBRA HA proteins (X1, X3, X6, and P1) had the broadest hemagglutination inhibition (HAI) activity against a panel of 17 H1N1 viruses. These vaccines were used in cocktails or prime-boost combinations. The most effective regimens that both elicited the broadest HAI response and protected mice against a pandemic H1N1 challenge were vaccines that contained the P1 COBRA VLP and either the X3 or X6 COBRA VLP vaccine. These mice had little or no detectable viral replication, comparable to that observed with a matched licensed vaccine. This is the first report describing a COBRA-based HA vaccine strategy that elicits a universal, broadly reactive, protective response against seasonal and pandemic H1N1 isolates. IMPORTANCE Universal influenza vaccine approaches have the potential to be paradigm shifting for the influenza vaccine field, with the goal of replacing the current standard of care with broadly cross-protective vaccines. We have used COBRA technology to develop an HA head-based strategy that elicits antibodies against many H1 strains that have undergone genetic drift and has potential as a “subtype universal” vaccine. Nine HA COBRA candidates were developed, and these vaccines were used alone, in cocktails or in prime-boost combinations. The most effective regimens elicited the broadest hemagglutination inhibition (HAI) response against a panel of H1N1 viruses isolated over the past 100 years. This is the first report describing a COBRA-based HA vaccine strategy that elicits a broadly reactive response against seasonal and pandemic H1N1 isolates. PMID:26912624
Maltby, Lorraine; van den Brink, Paul J; Faber, Jack H; Marshall, Stuart
2018-04-15
The ecosystem services (ES) approach is gaining broad interest in regulatory and policy arenas for use in landscape management and ecological risk assessment. It has the potential to bring greater ecological relevance to the setting of environmental protection goals and to the assessment of the ecological risk posed by chemicals. A workshop, organised under the auspices of the Society of Environmental Toxicology and Chemistry Europe, brought together scientific experts from European regulatory authorities, the chemical industry and academia to discuss and evaluate the challenges associated with implementing an ES approach to chemical ecological risk assessment (ERA). Clear advantages of using an ES approach in prospective and retrospective ERA were identified, including: making ERA spatially explicit and of relevance to management decisions (i.e. indicating what ES to protect and where); improving transparency in communicating risks and trade-offs; integrating across multiple stressors, scales, habitats and policies. A number of challenges were also identified including: the potential for increased complexity in assessments; greater data requirements; limitations in linking endpoints derived from current ecotoxicity tests to impacts on ES. In principle, the approach was applicable to all chemical sectors, but the scale of the challenge of applying an ES approach to general chemicals with widespread and dispersive uses leading to broad environmental exposure, was highlighted. There was agreement that ES-based risk assessment should be based on the magnitude of impact rather than on toxicity thresholds. The need for more bioassays/tests with functional endpoints was recognized, as was the role of modelling and the need for ecological production functions to link measurement endpoints to assessment endpoints. Finally, the value of developing environmental scenarios that can be combined with spatial information on exposure, ES delivery and service provider vulnerability was recognized. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Burnum-Johnson, Kristin E.; Nie, Song; Casey, Cameron P.
Current proteomics approaches are comprised of both broad discovery measurements as well as more quantitative targeted measurements. These two different measurement types are used to initially identify potentially important proteins (e.g., candidate biomarkers) and then enable improved quantification for a limited number of selected proteins. However, both approaches suffer from limitations, particularly the lower sensitivity, accuracy, and quantitation precision for discovery approaches compared to targeted approaches, and the limited proteome coverage provided by targeted approaches. Herein, we describe a new proteomics approach that allows both discovery and targeted monitoring (DTM) in a single analysis using liquid chromatography, ion mobility spectrometrymore » and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled peptides for target ions are spiked into tryptic digests and both the labeled and unlabeled peptides are broadly detected using LC-IMS-MS instrumentation, allowing the benefits of discovery and targeted approaches. To understand the possible improvement of the DTM approach, it was compared to LC-MS broad measurements using an accurate mass and time tag database and selected reaction monitoring (SRM) targeted measurements. The DTM results yielded greater peptide/protein coverage and a significant improvement in the detection of lower abundance species compared to LC-MS discovery measurements. DTM was also observed to have similar detection limits as SRM for the targeted measurements indicating its potential for combining the discovery and targeted approaches.« less
Keypress-Based Musical Preference Is Both Individual and Lawful.
Livengood, Sherri L; Sheppard, John P; Kim, Byoung W; Malthouse, Edward C; Bourne, Janet E; Barlow, Anne E; Lee, Myung J; Marin, Veronica; O'Connor, Kailyn P; Csernansky, John G; Block, Martin P; Blood, Anne J; Breiter, Hans C
2017-01-01
Musical preference is highly individualized and is an area of active study to develop methods for its quantification. Recently, preference-based behavior, associated with activity in brain reward circuitry, has been shown to follow lawful, quantifiable patterns, despite broad variation across individuals. These patterns, observed using a keypress paradigm with visual stimuli, form the basis for relative preference theory (RPT). Here, we sought to determine if such patterns extend to non-visual domains (i.e., audition) and dynamic stimuli, potentially providing a method to supplement psychometric, physiological, and neuroimaging approaches to preference quantification. For this study, we adapted our keypress paradigm to two sets of stimuli consisting of seventeenth to twenty-first century western art music (Classical) and twentieth to twenty-first century jazz and popular music (Popular). We studied a pilot sample and then a separate primary experimental sample with this paradigm, and used iterative mathematical modeling to determine if RPT relationships were observed with high R 2 fits. We further assessed the extent of heterogeneity in the rank ordering of keypress-based responses across subjects. As expected, individual rank orderings of preferences were quite heterogeneous, yet we observed mathematical patterns fitting these data similar to those observed previously with visual stimuli. These patterns in music preference were recurrent across two cohorts and two stimulus sets, and scaled between individual and group data, adhering to the requirements for lawfulness. Our findings suggest a general neuroscience framework that predicts human approach/avoidance behavior, while also allowing for individual differences and the broad diversity of human choices; the resulting framework may offer novel approaches to advancing music neuroscience, or its applications to medicine and recommendation systems.
Keypress-Based Musical Preference Is Both Individual and Lawful
Livengood, Sherri L.; Sheppard, John P.; Kim, Byoung W.; Malthouse, Edward C.; Bourne, Janet E.; Barlow, Anne E.; Lee, Myung J.; Marin, Veronica; O'Connor, Kailyn P.; Csernansky, John G.; Block, Martin P.; Blood, Anne J.; Breiter, Hans C.
2017-01-01
Musical preference is highly individualized and is an area of active study to develop methods for its quantification. Recently, preference-based behavior, associated with activity in brain reward circuitry, has been shown to follow lawful, quantifiable patterns, despite broad variation across individuals. These patterns, observed using a keypress paradigm with visual stimuli, form the basis for relative preference theory (RPT). Here, we sought to determine if such patterns extend to non-visual domains (i.e., audition) and dynamic stimuli, potentially providing a method to supplement psychometric, physiological, and neuroimaging approaches to preference quantification. For this study, we adapted our keypress paradigm to two sets of stimuli consisting of seventeenth to twenty-first century western art music (Classical) and twentieth to twenty-first century jazz and popular music (Popular). We studied a pilot sample and then a separate primary experimental sample with this paradigm, and used iterative mathematical modeling to determine if RPT relationships were observed with high R2 fits. We further assessed the extent of heterogeneity in the rank ordering of keypress-based responses across subjects. As expected, individual rank orderings of preferences were quite heterogeneous, yet we observed mathematical patterns fitting these data similar to those observed previously with visual stimuli. These patterns in music preference were recurrent across two cohorts and two stimulus sets, and scaled between individual and group data, adhering to the requirements for lawfulness. Our findings suggest a general neuroscience framework that predicts human approach/avoidance behavior, while also allowing for individual differences and the broad diversity of human choices; the resulting framework may offer novel approaches to advancing music neuroscience, or its applications to medicine and recommendation systems. PMID:28512395
Quantitative and qualitative approaches to identifying migration chronology in a continental migrant
Beatty, William S.; Kesler, Dylan C.; Webb, Elisabeth B.; Raedeke, Andrew H.; Naylor, Luke W.; Humburg, Dale D.
2013-01-01
The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos) equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international), whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result, targeted conservation plans can be developed to support planning for habitat management and evaluation of long-term climate effects.
Beatty, William S; Kesler, Dylan C; Webb, Elisabeth B; Raedeke, Andrew H; Naylor, Luke W; Humburg, Dale D
2013-01-01
The degree to which extrinsic factors influence migration chronology in North American waterfowl has not been quantified, particularly for dabbling ducks. Previous studies have examined waterfowl migration using various methods, however, quantitative approaches to define avian migration chronology over broad spatio-temporal scales are limited, and the implications for using different approaches have not been assessed. We used movement data from 19 female adult mallards (Anas platyrhynchos) equipped with solar-powered global positioning system satellite transmitters to evaluate two individual level approaches for quantifying migration chronology. The first approach defined migration based on individual movements among geopolitical boundaries (state, provincial, international), whereas the second method modeled net displacement as a function of time using nonlinear models. Differences in migration chronologies identified by each of the approaches were examined with analysis of variance. The geopolitical method identified mean autumn migration midpoints at 15 November 2010 and 13 November 2011, whereas the net displacement method identified midpoints at 15 November 2010 and 14 November 2011. The mean midpoints for spring migration were 3 April 2011 and 20 March 2012 using the geopolitical method and 31 March 2011 and 22 March 2012 using the net displacement method. The duration, initiation date, midpoint, and termination date for both autumn and spring migration did not differ between the two individual level approaches. Although we did not detect differences in migration parameters between the different approaches, the net displacement metric offers broad potential to address questions in movement ecology for migrating species. Ultimately, an objective definition of migration chronology will allow researchers to obtain a comprehensive understanding of the extrinsic factors that drive migration at the individual and population levels. As a result, targeted conservation plans can be developed to support planning for habitat management and evaluation of long-term climate effects.
Reinhold, William C
2015-12-10
There is currently a split within the cancer research community between traditional molecular biological hypothesis-driven and the more recent "omic" forms or research. While the molecular biological approach employs the tried and true single alteration-single response formulations of experimentation, the omic employs broad-based assay or sample collection approaches that generate large volumes of data. How to integrate the benefits of these two approaches in an efficient and productive fashion remains an outstanding issue. Ideally, one would merge the understandability, exactness, simplicity, and testability of the molecular biological approach, with the larger amounts of data, simultaneous consideration of multiple alterations, consideration of genes both of known interest along with the novel, cross-sample comparisons among cell lines and patient samples, and consideration of directed questions while simultaneously gaining exposure to the novel provided by the omic approach. While at the current time integration of the two disciplines remains problematic, attempts to do so are ongoing, and will be necessary for the understanding of the large cell line screens including the Developmental Therapeutics Program's NCI-60, the Broad Institute's Cancer Cell Line Encyclopedia, and the Wellcome Trust Sanger Institute's Cancer Genome Project, as well as the the Cancer Genome Atlas clinical samples project. Going forward there is significant benefit to be had from the integration of the molecular biological and the omic forms or research, with the desired goal being improved translational understanding and application.
Applications of Advanced, Waveform Based AE Techniques for Testing Composite Materials
NASA Technical Reports Server (NTRS)
Prosser, William H.
1996-01-01
Advanced, waveform based acoustic emission (AE) techniques have been previously used to evaluate damage progression in laboratory tests of composite coupons. In these tests, broad band, high fidelity acoustic sensors were used to detect signals which were then digitized and stored for analysis. Analysis techniques were based on plate mode wave propagation characteristics. This approach, more recently referred to as Modal AE, provides an enhanced capability to discriminate and eliminate noise signals from those generated by damage mechanisms. This technique also allows much more precise source location than conventional, threshold crossing arrival time determination techniques. To apply Modal AE concepts to the interpretation of AE on larger composite structures, the effects of wave propagation over larger distances and through structural complexities must be well characterized and understood. In this research, measurements were made of the attenuation of the extensional and flexural plate mode components of broad band simulated AE signals in large composite panels. As these materials have applications in a cryogenic environment, the effects of cryogenic insulation on the attenuation of plate mode AE signals were also documented.
Porquez, Jeremy G.; Cole, Ryan A.; Tabarangao, Joel T.; Slepkov, Aaron D.
2016-01-01
We demonstrate spectral-focusing based coherent anti-Stokes Raman scattering (SF-CARS) hyper-microscopy capable of probing vibrational frequencies from 630 cm−1 to 3250 cm−1 using a single Ti:Sapphire femtosecond laser operating at 800 nm, and a commercially-available supercontinuum-generating fibre module. A broad Stokes supercontinuum with significant spectral power at wavelengths between 800 nm and 940 nm is generated by power tuning the fibre module using atypically long and/or chirped ~200 fs pump pulses, allowing convenient access to lower vibrational frequencies in the fingerprint spectral region. This work significantly reduces the instrumental and technical requirements for multimodal CARS microscopy, while expanding the spectral capabilities of an established approach to SF-CARS. PMID:27867735
Space Propulsion Synergy Group ETO technology assessments
NASA Astrophysics Data System (ADS)
Bray, James
The Space Propulsion Synergy Group (SPSG), which was chartered to support long-range strategic planning, has, using a broad industry/government team, evaluated and achieved consensus on the vehicles, propulsion systems, and propulsion technologies that have the best long-term potential for achieving desired system attributes. The breakthrough that enabled broad consensus was developing criteria that are measurable a priori. The SPSG invented a dual prioritization approach that balances long-term strategic thrusts with current programmatic constraints. This enables individual program managers to make decisions based on both individual project needs and long-term strategic needs. Results indicate that an SSTO using an integrated modular engine has the best long-term potential for a 20 Klb class vehicle, and that health monitoring and control technologies are among the highest dual priority liquid rocket technologies.
NASA Astrophysics Data System (ADS)
Woodbridge, Jessie; Roberts, Neil; Fyfe, Ralph; Gaillard, Marie-José; Trondman, Anna-Kari; Davis, Basil; Kaplan, Jed
2016-04-01
Europe's primaeval forests have been progressively cleared and fragmented since the first appearance of Neolithic farming activities around 6000 years ago. Understanding spatial and temporal changes in forest cover is valuable to researchers interested in past human-environment interactions. Here we present a comparison of reconstructed Holocene forest cover across Europe from three different transformed fossil pollen-based datasets, an extensive modern surface pollen data set, and modern forest cover from remote sensing. The REVEALS approach (Trondman et al., 2015) provides a quantified and validated reconstruction of vegetation incorporating plant productivity estimates, but is currently only available for a limited number of grid cells in mid-latitude and northern Europe for a limited number of time windows. The pseudobiomization (PBM) (Fyfe et al., 2015) and plant functional type (PFT) (Davis et al., 2015) based approaches provide continuous semi-quantitative records of land use change for temperate and Northern Europe spanning the Holocene, but do not provide truly quantified vegetation reconstructions. Estimated modern forest cover based on the various approaches ranges between ~29 and 54%. However, the Holocene estimates of vegetation change show broadly similar trends, with a forest maximum from ~8.2 to ~6 ka BP, and a decline in forest cover after 6 ka BP, accelerating after ~1.2 ka BP. The reconstructions, when broadly disaggregated into northern and mid-latitude Europe, confirm that mid-latitude forest cover has declined more than that in northern Europe over the last 6 ka. The continuous record provided by the PBM has been used to establish a 'half forest loss' date for each grid cell in temperate and northern Europe, which has identified that the timing of forest loss varied spatially with certain regions remaining forested for longer. References Davis BAS, Collins PM, Kaplan JO (2015) The age and post-glacial development of the modern European vegetation: a plant functional approach based on pollen data. Vegetation History and Archaeobotany. 24, 303-317. Fyfe RM, Woodbridge J and Roberts N (2015) From forest to farmland: pollen-inferred land cover change across Europe using the pseudobiomization approach. Global Change Biology 20, 1197-1212. Trondman A-K, Gaillard M-J, Sugita S et al. (2015) Pollen-based land-cover reconstructions for the study of past vegetation-climate interactions in NW Europe at 0.2 k, 0.5 k, 3 k and 6 k years before present. Global Change Biology. 21, 676-697.
Tishelman, Carol
2018-01-01
Public health and health promotion approaches to end-of-life (EoL) research and care are still rare in Sweden. People remain generally ill-prepared for encounters with death and unable to advocate for quality EoL care; this may be reflected in Sweden's low scores for community engagement in the 2015 Quality of Death index. We have consolidated our endeavours into a cohesive national transdisciplinary research program, DöBra (a pun meaning both 'dying well' and 'awesome' in Swedish). In DöBra, we investigate how culture, the environment and conversation can promote constructive change and support better quality of life and death among the general population, in specific subgroups and in interventions directed to staff caring for dying individuals, their friends and families. DöBra uses ideas from new public health and the Ottawa Charter as umbrella theoretical frameworks and participatory action research as an overarching methodological approach. In DöBra we aim to achieve change in communities in a broad sense. In this interactive workshop, we therefore focus on the particular challenges we encounter in conducting stringent research when trying to catalyse, rather than control, change processes. We will share our ideas, experiences, reflections, tools and approaches as well as results, related to using a variety of strategies to bring together a broad range of stakeholders to co-create experience-based evidence through innovative approaches. We begin by linking theory, research and practice through discussion of the overarching ideas and individual projects, with the second part of the session based on audience engagement with various tools used in DöBra.
A fully probabilistic approach to extreme rainfall modeling
NASA Astrophysics Data System (ADS)
Coles, Stuart; Pericchi, Luis Raúl; Sisson, Scott
2003-03-01
It is an embarrassingly frequent experience that statistical practice fails to foresee historical disasters. It is all too easy to blame global trends or some sort of external intervention, but in this article we argue that statistical methods that do not take comprehensive account of the uncertainties involved in both model and predictions, are bound to produce an over-optimistic appraisal of future extremes that is often contradicted by observed hydrological events. Based on the annual and daily rainfall data on the central coast of Venezuela, different modeling strategies and inference approaches show that the 1999 rainfall which caused the worst environmentally related tragedy in Venezuelan history was extreme, but not implausible given the historical evidence. We follow in turn a classical likelihood and Bayesian approach, arguing that the latter is the most natural approach for taking into account all uncertainties. In each case we emphasize the importance of making inference on predicted levels of the process rather than model parameters. Our most detailed model comprises of seasons with unknown starting points and durations for the extremes of daily rainfall whose behavior is described using a standard threshold model. Based on a Bayesian analysis of this model, so that both prediction uncertainty and process heterogeneity are properly modeled, we find that the 1999 event has a sizeable probability which implies that such an occurrence within a reasonably short time horizon could have been anticipated. Finally, since accumulation of extreme rainfall over several days is an additional difficulty—and indeed, the catastrophe of 1999 was exaggerated by heavy rainfall on successive days—we examine the effect of timescale on our broad conclusions, finding results to be broadly similar across different choices.
Falke, Jeffrey A.; Dunham, Jason B.; Hockman-Wert, David; Pahl, Randy
2016-01-01
We provide a simple framework for diagnosing the impairment of stream water temperature for coldwater fishes across broad spatial extents based on a weight-of-evidence approach that integrates biological criteria, species distribution models, and geostatistical models of stream temperature. As a test case, we applied our approach to identify stream reaches most likely to be thermally impaired for Lahontan Cutthroat Trout Oncorhynchus clarkii henshawi in the upper Reese River, located in the northern Great Basin, Nevada. We first evaluated the capability of stream thermal regime descriptors to explain variation across 170 sites, and we found that the 7-d moving average of daily maximum stream temperatures (7DADM) provided minimal among-descriptor redundancy and, based on an upper threshold of 20°C, was also a good indicator of acute and chronic thermal stress. Next, we quantified the range of Lahontan Cutthroat Trout within our study area using a geographic distribution model. Finally, we used a geostatistical model to assess spatial variation in 7DADM and predict potential thermal impairment at the stream reach scale. We found that whereas 38% of reaches in our study area exceeded a 7DADM of 20°C and 35% were significantly warmer than predicted, only 17% both exceeded the biological criterion and were significantly warmer than predicted. This filtering allowed us to identify locations where physical and biological impairment were most likely within the network and that would represent the highest management priorities. Although our approach lacks the precision of more comprehensive approaches, it provides a broader context for diagnosing impairment and is a useful means of identifying priorities for more detailed evaluations across broad and heterogeneous stream networks.
Thiel, William H.; Bair, Thomas; Peek, Andrew S.; Liu, Xiuying; Dassie, Justin; Stockdale, Katie R.; Behlke, Mark A.; Miller, Francis J.; Giangrande, Paloma H.
2012-01-01
Background The broad applicability of RNA aptamers as cell-specific delivery tools for therapeutic reagents depends on the ability to identify aptamer sequences that selectively access the cytoplasm of distinct cell types. Towards this end, we have developed a novel approach that combines a cell-based selection method (cell-internalization SELEX) with high-throughput sequencing (HTS) and bioinformatics analyses to rapidly identify cell-specific, internalization-competent RNA aptamers. Methodology/Principal Findings We demonstrate the utility of this approach by enriching for RNA aptamers capable of selective internalization into vascular smooth muscle cells (VSMCs). Several rounds of positive (VSMCs) and negative (endothelial cells; ECs) selection were performed to enrich for aptamer sequences that preferentially internalize into VSMCs. To identify candidate RNA aptamer sequences, HTS data from each round of selection were analyzed using bioinformatics methods: (1) metrics of selection enrichment; and (2) pairwise comparisons of sequence and structural similarity, termed edit and tree distance, respectively. Correlation analyses of experimentally validated aptamers or rounds revealed that the best cell-specific, internalizing aptamers are enriched as a result of the negative selection step performed against ECs. Conclusions and Significance We describe a novel approach that combines cell-internalization SELEX with HTS and bioinformatics analysis to identify cell-specific, cell-internalizing RNA aptamers. Our data highlight the importance of performing a pre-clear step against a non-target cell in order to select for cell-specific aptamers. We expect the extended use of this approach to enable the identification of aptamers to a multitude of different cell types, thereby facilitating the broad development of targeted cell therapies. PMID:22962591
Miri, Andrew; Daie, Kayvon; Burdine, Rebecca D.; Aksay, Emre
2011-01-01
The advent of methods for optical imaging of large-scale neural activity at cellular resolution in behaving animals presents the problem of identifying behavior-encoding cells within the resulting image time series. Rapid and precise identification of cells with particular neural encoding would facilitate targeted activity measurements and perturbations useful in characterizing the operating principles of neural circuits. Here we report a regression-based approach to semiautomatically identify neurons that is based on the correlation of fluorescence time series with quantitative measurements of behavior. The approach is illustrated with a novel preparation allowing synchronous eye tracking and two-photon laser scanning fluorescence imaging of calcium changes in populations of hindbrain neurons during spontaneous eye movement in the larval zebrafish. Putative velocity-to-position oculomotor integrator neurons were identified that showed a broad spatial distribution and diversity of encoding. Optical identification of integrator neurons was confirmed with targeted loose-patch electrical recording and laser ablation. The general regression-based approach we demonstrate should be widely applicable to calcium imaging time series in behaving animals. PMID:21084686
Barratt, Alexandra
2008-12-01
Evidence Based Medicine (EBM) and Shared Medical Decision Making (SDM) are changing the nature of health care decisions. It is broadly accepted that health care decisions require the integration of research evidence and individual preferences. These approaches are justified on both efficacy grounds (that evidence based practice and Shared Decision Making should lead to better health outcomes and may lead to a more cost-effective use of health care resources) and ethical grounds (patients' autonomy should be respected in health care). However, despite endorsement by physicians and consumers of these approaches, implementation remains limited in practice, particularly outside academic and tertiary health care centres. There are practical problems of implementation, which include training, access to research, and development of and access to tools to display evidence and support decision making. There may also be philosophical difficulties, and some have even suggested that the two approaches (evidence based practice and Shared Decision Making) are fundamentally incompatible. This paper look at the achievements of EBM and SDM so far, the potential tensions between them, and how things might progress in the future.
Comparison of PA imaging by narrow beam scanning and one-shot broad beam excitation
NASA Astrophysics Data System (ADS)
Xia, Jinjun; Wei, Chen-Wei; Huang, Lingyun; Pelivanov, I. M.; O'Donnell, Matthew
2011-03-01
Current systems designed for deep photoacoustic (PA) imaging typically use a low repetition rate, high power pulsed laser to provide a ns-scale pulse illuminating a large tissue volume. Acoustic signals recorded on each laser firing can be used to reconstruct a complete 2-D (3-D) image of sources of heat release within that region. Using broad-beam excitation, the maximum frame rate of the imaging system is restricted by the pulse repetition rate of the laser. An alternate illumination approach is proposed based on fast scanning by a low energy (~ 1 mJ) high repetition rate (up to a few kHz) narrow laser beam (~1 mm) along the tissue surface over a region of interest. A final PA image is produced from the summation of individual PA images reconstructed at each laser beam position. This concept can take advantage of high repetition rate fiber lasers to create PA images with much higher frame rates than current systems, enabling true real-time integration of photoacoustics with ultrasound imaging. As an initial proof of concept, we compare conventional broad beam illumination to a scanned beam approach in a simple model system. Two transparent teflon tubes with diameters of 1.6 mm and 0.8 mm were filled with ink having an absorption coefficient of 5 cm-1. These tubes were buried inside chicken breast tissue acting as an optical scattering medium. They were separated by 3 mm or 10 mm to test spatial and contrast resolution for the two scan formats. The excitation wavelength was 700 nm. The excitation source is a traditional OPO pumped by a Q-switched Nd:YAG laser with doubler. Photoacoustic images were reconstructed using signals from a small, scanned PVDF transducer acting as an acoustic array. Two different illumination schemes were compared: one was 15 mm x 10 mm in cross section and acted as the broad beam; the other was 5 mm x 2 mm in cross section (15 times smaller than the broad beam case) and was scanned over an area equivalent to broad beam illumination. Multiple images obtained during narrow beam scanning were added together to form one PA image equivalent to the single-shot broad beam one. Results of the phantom study indicate that PA images formed by narrow beam scanning excitation can be equivalent to one shot broad beam illumination in signal to noise ratio and spatial resolution. Future studies will focus on high repetition-rate laser sources and scan formats appropriate for real-time, integrated deep photoacoustic/ultrasonic imaging.
Wang, Jiqiang
2016-03-01
Restricted sensing and actuation control represents an important area of research that has been overlooked in most of the design methodologies. In many practical control engineering problems, it is necessitated to implement the design through a single sensor and single actuator for multivariate performance variables. In this paper, a novel approach is proposed for the solution to the single sensor and single actuator control problem where performance over any prescribed frequency band can also be tailored. The results are obtained for the broad band control design based on the formulation for discrete frequency control. It is shown that the single sensor and single actuator control problem over a frequency band can be cast into a Nevanlinna-Pick interpolation problem. An optimal controller can then be obtained via the convex optimization over LMIs. Even remarkable is that robustness issues can also be tackled in this framework. A numerical example is provided for the broad band attenuation of rotor blade vibration to illustrate the proposed design procedures. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.
Development of vaccines against meningococcal disease.
Jódar, Luis; Feavers, Ian M; Salisbury, David; Granoff, Dan M
2002-04-27
Neisseria meningitidis is a major cause of bacterial meningitis and sepsis. Polysaccharide-protein conjugate vaccines for prevention of group C disease have been licensed in Europe. Such vaccines for prevention of disease caused by groups A (which is associated with the greatest disease burden worldwide), Y, and W135 are being developed. However, conventional approaches to develop a vaccine for group B strains, which are responsible for most cases in Europe and the USA, have been largely unsuccessful. Capsular polysaccharide-based vaccines can elicit autoantibodies to host polysialic acid, whereas the ability of most non-capsular antigens to elicit broad-based immunity is limited by their antigenic diversity. Many new membrane proteins have been discovered during analyses of genomic sequencing data. These antigens are highly conserved and, in mice, elicit serum bactericidal antibodies, which are the serological hallmark of protective immunity in man. Therefore, there are many promising new vaccine candidates, and improved prospects for development of a broadly protective vaccine for group B disease, and for control of all meningococcal disease.
NASA Astrophysics Data System (ADS)
Bianchi, Marco; Pedretti, Daniele
2017-04-01
We present an approach to predict non-Fickian transport behaviour in alluvial aquifers from knowledge of physical heterogeneity. This parsimonious approach is based on only two measurable parameters describing the global variability and the structure of the hydraulic conductivity (K) field: the variance of the ln(K) values (σY 2), and a newly developed index of geological entropy (HR), based on the concept of Shannon information entropy. Both σY 2 and HR can be obtained from data collected during conventional hydrogeological investigations and from the analysis of a representative model of the spatial distribution of K classes (e.g. hydrofacies) over the domain of interest. The new index HR integrates multiple characteristics of the K field, including the presence of well-connected features, into a unique metric that quantifies the degrees of spatial disorder in the K field structure. Stochastic simulations of tracer tests in synthetic K fields based on realistic distributions of hydrofacies in alluvial aquifers are conducted to identify empirical relations between HR, σY 2, and the first three central temporal moments of the resulting breakthrough curves (BTCs). Results indicate that the first and second moments tend to increase with spatial disorder (i.e, HR increasing). Conversely, high values of the third moment (i.e. skewness), which indicate significant post-peak tailing in the BTCs and non-Fickian transport behaviour, are observed in more orderly structures (i.e, HR decreasing), or for very high σY 2 values. We show that simple closed-form empirical expressions can be derived to describe the bivariate dependency between the skewness of the BTC and corresponding pairs of HR and σY 2. This dependency shows clear correlation for a broad range of structures and Kvariability levels. Therefore, it provides an effective and broadly applicable approach to explain and predict non-Fickian transport in real aquifers, such as those at the well-known MADE site and at the Lawrence Livermore National Laboratory.
Ortega, Julio; Asensio-Cubero, Javier; Gan, John Q; Ortiz, Andrés
2016-07-15
Brain-computer interfacing (BCI) applications based on the classification of electroencephalographic (EEG) signals require solving high-dimensional pattern classification problems with such a relatively small number of training patterns that curse of dimensionality problems usually arise. Multiresolution analysis (MRA) has useful properties for signal analysis in both temporal and spectral analysis, and has been broadly used in the BCI field. However, MRA usually increases the dimensionality of the input data. Therefore, some approaches to feature selection or feature dimensionality reduction should be considered for improving the performance of the MRA based BCI. This paper investigates feature selection in the MRA-based frameworks for BCI. Several wrapper approaches to evolutionary multiobjective feature selection are proposed with different structures of classifiers. They are evaluated by comparing with baseline methods using sparse representation of features or without feature selection. The statistical analysis, by applying the Kolmogorov-Smirnoff and Kruskal-Wallis tests to the means of the Kappa values evaluated by using the test patterns in each approach, has demonstrated some advantages of the proposed approaches. In comparison with the baseline MRA approach used in previous studies, the proposed evolutionary multiobjective feature selection approaches provide similar or even better classification performances, with significant reduction in the number of features that need to be computed.
Commentary: The failure of social inclusion: an alternative approach through community development.
Mandiberg, James M
2012-01-01
Mental health services have not resulted in broad-based inclusion of people with psychiatric disabilities. Rather, many maintain their community lives only through the support of formal mental health services, which is financially unsustainable given current fiscal realities. Fundamental assumptions about sources of support for everyday life need to be reassessed. The economic and social development of the mental health recovery community provides an alternative approach to helping people maintain successful community lives and shifts some of the supports from mental health providers to business infrastructure within the mental health recovery identity community. Some projects that have utilized this approach, such as business incubators and work integration social enterprises, are described, and community development that builds on concepts of recovery is discussed.
Design of Reflective, Photonic Shields for Atmospheric Reentry
NASA Technical Reports Server (NTRS)
Komarevskiy, Nikolay; Shklover, Valery; Braginsky, Leonid; Hafner, Christian; Fabrichnaya, Olga; White, Susan; Lawson, John
2010-01-01
We present the design of one-dimensional photonic crystal structures, which can be used as omnidirectional reflecting shields against radiative heating of space vehicles entering the Earth's atmosphere. This radiation is approximated by two broad bands centered at visible and near-infrared energies. We applied two approaches to find structures with the best omnidirectional reflecting performance. The first approach is based on a band gap analysis and leads to structures composed of stacked Bragg mirrors. In the second approach, we optimize the structure using an evolutionary strategy. The suggested structures are compared with a simple design of two stacked Bragg mirrors. Choice of the constituent materials for the layers as well as the influence of interlayer diffusion at high temperatures are discussed.
New Approaches to the Synthesis of Novel Organosilanes.
1983-10-01
through" electrode composed of RVC ( reticulated vitreous carbon ), a highly conductive sponge of carbonized material. Both of these flow systems...effective in promoting silicon- carbon bond cleavage and reformation to give cyclic and cage compounds readily and in good yields: (tA*3-9)(CŖ). n 2-S...silicon to carbon bonds and has broad based applications in research and industrial labs. The increase in reaction rate and yield with ultrasonic waves
An IT-enabled supply chain model: a simulation study
NASA Astrophysics Data System (ADS)
Cannella, Salvatore; Framinan, Jose M.; Barbosa-Póvoa, Ana
2014-11-01
During the last decades, supply chain collaboration practices and the underlying enabling technologies have evolved from the classical electronic data interchange (EDI) approach to a web-based and radio frequency identification (RFID)-enabled collaboration. In this field, most of the literature has focused on the study of optimal parameters for reducing the total cost of suppliers, by adopting operational research (OR) techniques. Herein we are interested in showing that the considered information technology (IT)-enabled structure is resilient, that is, it works well across a reasonably broad range of parameter settings. By adopting a methodological approach based on system dynamics, we study a multi-tier collaborative supply chain. Results show that the IT-enabled supply chain improves operational performance and customer service level. Nonetheless, benefits for geographically dispersed networks are of minor entity.
NASA Technical Reports Server (NTRS)
Maddalon, J. M.; Hayhurst, K. J.; Neogi, N. A.; Verstynen, H. A.; Clothier, R. A.
2016-01-01
One of the key challenges to the development of a commercial Unmanned Air-craft System (UAS) market is the lack of explicit consideration of UAS in the current regulatory framework. Despite recent progress, additional steps are needed to enable broad UAS types and operational models. This paper discusses recent research that examines how a risk-based approach for safety might change the process and substance of airworthiness requirements for UAS. The project proposed risk-centric airworthiness requirements for a midsize un-manned rotorcraft used for agricultural spraying and also identified factors that may contribute to distinguishing safety risk among different UAS types and operational concepts. Lessons learned regarding how a risk-based approach can expand the envelope of UAS certification are discussed.
Obesity prevention: Comparison of techniques and potential solution
NASA Astrophysics Data System (ADS)
Zulkepli, Jafri; Abidin, Norhaslinda Zainal; Zaibidi, Nerda Zura
2014-12-01
Over the years, obesity prevention has been a broadly studied subject by both academicians and practitioners. It is one of the most serious public health issue as it can cause numerous chronic health and psychosocial problems. Research is needed to suggest a population-based strategy for obesity prevention. In the academic environment, the importance of obesity prevention has triggered various problem solving approaches. A good obesity prevention model, should comprehend and cater all complex and dynamics issues. Hence, the main purpose of this paper is to discuss the qualitative and quantitative approaches on obesity prevention study and to provide an extensive literature review on various recent modelling techniques for obesity prevention. Based on these literatures, the comparison of both quantitative and qualitative approahes are highlighted and the justification on the used of system dynamics technique to solve the population of obesity is discussed. Lastly, a potential framework solution based on system dynamics modelling is proposed.
Simulation methods to estimate design power: an overview for applied research.
Arnold, Benjamin F; Hogan, Daniel R; Colford, John M; Hubbard, Alan E
2011-06-20
Estimating the required sample size and statistical power for a study is an integral part of study design. For standard designs, power equations provide an efficient solution to the problem, but they are unavailable for many complex study designs that arise in practice. For such complex study designs, computer simulation is a useful alternative for estimating study power. Although this approach is well known among statisticians, in our experience many epidemiologists and social scientists are unfamiliar with the technique. This article aims to address this knowledge gap. We review an approach to estimate study power for individual- or cluster-randomized designs using computer simulation. This flexible approach arises naturally from the model used to derive conventional power equations, but extends those methods to accommodate arbitrarily complex designs. The method is universally applicable to a broad range of designs and outcomes, and we present the material in a way that is approachable for quantitative, applied researchers. We illustrate the method using two examples (one simple, one complex) based on sanitation and nutritional interventions to improve child growth. We first show how simulation reproduces conventional power estimates for simple randomized designs over a broad range of sample scenarios to familiarize the reader with the approach. We then demonstrate how to extend the simulation approach to more complex designs. Finally, we discuss extensions to the examples in the article, and provide computer code to efficiently run the example simulations in both R and Stata. Simulation methods offer a flexible option to estimate statistical power for standard and non-traditional study designs and parameters of interest. The approach we have described is universally applicable for evaluating study designs used in epidemiologic and social science research.
Simulation methods to estimate design power: an overview for applied research
2011-01-01
Background Estimating the required sample size and statistical power for a study is an integral part of study design. For standard designs, power equations provide an efficient solution to the problem, but they are unavailable for many complex study designs that arise in practice. For such complex study designs, computer simulation is a useful alternative for estimating study power. Although this approach is well known among statisticians, in our experience many epidemiologists and social scientists are unfamiliar with the technique. This article aims to address this knowledge gap. Methods We review an approach to estimate study power for individual- or cluster-randomized designs using computer simulation. This flexible approach arises naturally from the model used to derive conventional power equations, but extends those methods to accommodate arbitrarily complex designs. The method is universally applicable to a broad range of designs and outcomes, and we present the material in a way that is approachable for quantitative, applied researchers. We illustrate the method using two examples (one simple, one complex) based on sanitation and nutritional interventions to improve child growth. Results We first show how simulation reproduces conventional power estimates for simple randomized designs over a broad range of sample scenarios to familiarize the reader with the approach. We then demonstrate how to extend the simulation approach to more complex designs. Finally, we discuss extensions to the examples in the article, and provide computer code to efficiently run the example simulations in both R and Stata. Conclusions Simulation methods offer a flexible option to estimate statistical power for standard and non-traditional study designs and parameters of interest. The approach we have described is universally applicable for evaluating study designs used in epidemiologic and social science research. PMID:21689447
Kotásková, Iva; Mališová, Barbora; Obručová, Hana; Holá, Veronika; Peroutková, Tereza; Růžička, Filip; Freiberger, Tomáš
2017-01-01
Complex samples are a challenge for sequencing-based broad-range diagnostics. We analysed 19 urinary catheter, ureteral Double-J catheter, and urine samples using 3 methodological approaches. Out of the total 84 operational taxonomic units, 37, 61, and 88% were identified by culture, PCR-DGGE-SS (PCR denaturing gradient gel electrophoresis followed by Sanger sequencing), and PCR-DGGE-RM (PCR- DGGE combined with software chromatogram separation by RipSeq Mixed tool), respectively. The latter approach was shown to be an efficient tool to complement culture in complex sample assessment. © 2017 S. Karger AG, Basel.
Improving Small Interfering RNA Delivery In Vivo Through Lipid Conjugation.
Osborn, Maire F; Khvorova, Anastasia
2018-05-10
RNA interference (RNAi)-based therapeutics are approaching clinical approval for genetically defined diseases. Current clinical success is a result of significant innovations in the development of chemical architectures that support sustained, multi-month efficacy in vivo following a single administration. Conjugate-mediated delivery has established itself as the most promising platform for safe and targeted small interfering RNA (siRNA) delivery. Lipophilic conjugates represent a major class of modifications that improve siRNA pharmacokinetics and enable efficacy in a broad range of tissues. Here, we review current literature and define key features and limitations of this approach for in vivo modulation of gene expression.
Corbin, Laura J; Tan, Vanessa Y; Hughes, David A; Wade, Kaitlin H; Paul, Dirk S; Tansey, Katherine E; Butcher, Frances; Dudbridge, Frank; Howson, Joanna M; Jallow, Momodou W; John, Catherine; Kingston, Nathalie; Lindgren, Cecilia M; O'Donavan, Michael; O'Rahilly, Stephen; Owen, Michael J; Palmer, Colin N A; Pearson, Ewan R; Scott, Robert A; van Heel, David A; Whittaker, John; Frayling, Tim; Tobin, Martin D; Wain, Louise V; Smith, George Davey; Evans, David M; Karpe, Fredrik; McCarthy, Mark I; Danesh, John; Franks, Paul W; Timpson, Nicholas J
2018-02-19
Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scenarios for the application of RbG: studies using single variants and those using multiple variants. We consider the efficacy and practicality of the RbG approach, provide a catalogue of UK-based resources for such studies and present an online RbG study planner.
Stenov, Vibeke; Hempler, Nana Folmann; Reventlow, Susanne; Wind, Gitte
2017-08-22
To investigate approaches among healthcare providers (HCPs) that support or hinder person-centredness in group-based diabetes education programmes targeting persons with type 2 diabetes. Ethnographic fieldwork in a municipal and a hospital setting in Denmark. The two programmes included 21 participants and 10 HCPs and were observed over 5 weeks. Additionally, 10 in-depth semi-structured interviews were conducted with patients (n = 7) and HCPs (n = 3). Data were analysed using systematic text condensation. Hindering approaches included a teacher-centred focus on delivering disease-specific information. Communication was dialog based, but HCPs primarily asked closed-ended questions with one correct answer. Additional hindering approaches included ignoring participants with suboptimal health behaviours and a tendency to moralize that resulted in feelings of guilt among participants. Supporting approaches included letting participants set the agenda using broad, open-ended questions. Healthcare providers are often socialized into a biomedical approach and trained to be experts. However, person-centredness involves redefined roles and responsibilities. Applying person-centredness in practice requires continuous training and supervision, but HCPs often have minimum support for developing person-centred communication skills. Techniques based on motivational communication, psychosocial methods and facilitating group processes are effective person-centred approaches in a group context. Teacher-centredness undermined person-centredness because HCPs primarily delivered disease-specific recommendations, leading to biomedical information overload for participants. © 2017 Nordic College of Caring Science.
Clinical decision making-a functional medicine perspective.
Pizzorno, Joseph E
2012-09-01
As 21st century health care moves from a disease-based approach to a more patient-centric system that can address biochemical individuality to improve health and function, clinical decision making becomes more complex. Accentuating the problem is the lack of a clear standard for this more complex functional medicine approach. While there is relatively broad agreement in Western medicine for what constitutes competent assessment of disease and identification of related treatment approaches, the complex functional medicine model posits multiple and individualized diagnostic and therapeutic approaches, most or many of which have reasonable underlying science and principles, but which have not been rigorously tested in a research or clinical setting. This has led to non-rigorous thinking and sometimes to uncritical acceptance of both poorly documented diagnostic procedures and ineffective therapies, resulting in less than optimal clinical care.
Clinical Decision Making—A Functional Medicine Perspective
2012-01-01
As 21st century health care moves from a disease-based approach to a more patient-centric system that can address biochemical individuality to improve health and function, clinical decision making becomes more complex. Accentuating the problem is the lack of a clear standard for this more complex functional medicine approach. While there is relatively broad agreement in Western medicine for what constitutes competent assessment of disease and identification of related treatment approaches, the complex functional medicine model posits multiple and individualized diagnostic and therapeutic approaches, most or many of which have reasonable underlying science and principles, but which have not been rigorously tested in a research or clinical setting. This has led to non-rigorous thinking and sometimes to uncritical acceptance of both poorly documented diagnostic procedures and ineffective therapies, resulting in less than optimal clinical care. PMID:24278827
McKenna, James E.; Carlson, Douglas M.; Payne-Wynne, Molly L.
2013-01-01
Aim: Rare aquatic species are a substantial component of biodiversity, and their conservation is a major objective of many management plans. However, they are difficult to assess, and their optimal habitats are often poorly known. Methods to effectively predict the likely locations of suitable rare aquatic species habitats are needed. We combine two modelling approaches to predict occurrence and general abundance of several rare fish species. Location: Allegheny watershed of western New York State (USA) Methods: Our method used two empirical neural network modelling approaches (species specific and assemblage based) to predict stream-by-stream occurrence and general abundance of rare darters, based on broad-scale habitat conditions. Species-specific models were developed for longhead darter (Percina macrocephala), spotted darter (Etheostoma maculatum) and variegate darter (Etheostoma variatum) in the Allegheny drainage. An additional model predicted the type of rare darter-containing assemblage expected in each stream reach. Predictions from both models were then combined inclusively and exclusively and compared with additional independent data. Results Example rare darter predictions demonstrate the method's effectiveness. Models performed well (R2 ≥ 0.79), identified where suitable darter habitat was most likely to occur, and predictions matched well to those of collection sites. Additional independent data showed that the most conservative (exclusive) model slightly underestimated the distributions of these rare darters or predictions were displaced by one stream reach, suggesting that new darter habitat types were detected in the later collections. Main conclusions Broad-scale habitat variables can be used to effectively identify rare species' habitats. Combining species-specific and assemblage-based models enhances our ability to make use of the sparse data on rare species and to identify habitat units most likely and least likely to support those species. This hybrid approach may assist managers with the prioritization of habitats to be examined or conserved for rare species.
Emerging applications of nanoparticles for lung cancer diagnosis and therapy
NASA Astrophysics Data System (ADS)
Sukumar, Uday Kumar; Bhushan, Bharat; Dubey, Poornima; Matai, Ishita; Sachdev, Abhay; Packirisamy, Gopinath
2013-07-01
Lung cancer is by far the leading cause of cancer-related mortality worldwide, most of them being active tobacco smokers. Non small cell lung cancer accounts for around 85% to 90% of deaths, whereas the rest is contributed by small cell lung cancer. The extreme lethality of lung cancer arises due to lack of suitable diagnostic procedures for early detection of lung cancer and ineffective conventional therapeutic strategies. In course with desperate attempts to address these issues independently, a multifunctional nanotherapeutic or diagnostic system is being sought as a favorable solution. The manifestation of physiochemical properties of such nanoscale systems is tuned favorably to come up with a versatile cancer cell targeted diagnostic and therapeutic system. Apart from this, the aspect of being at nanoscale by itself confers the system with an advantage of passive accumulation at the site of tumor. This review provides a broad perspective of three major subclasses of such nanoscale therapeutic and diagnostic systems which include polymeric nanoparticles-based approaches, metal nanoparticles-based approaches, and bio-nanoparticles-based approaches. This review work also serves the purpose of gaining an insight into the pros and cons of each of these approaches with a prospective improvement in lung cancer therapeutics and diagnostics.
A Vision-Based Approach for Building Telecare and Telerehabilitation Services.
Barriga, Angela; Conejero, José M; Hernández, Juan; Jurado, Elena; Moguel, Enrique; Sánchez-Figueroa, Fernando
2016-10-18
In the last few years, telerehabilitation and telecare have become important topics in healthcare since they enable people to remain independent in their own homes by providing person-centered technologies to support the individual. These technologies allows elderly people to be assisted in their home, instead of traveling to a clinic, providing them wellbeing and personalized health care. The literature shows a great number of interesting proposals to address telerehabilitation and telecare scenarios, which may be mainly categorized into two broad groups, namely wearable devices and context-aware systems. However, we believe that these apparently different scenarios may be addressed by a single context-aware approach, concretely a vision-based system that can operate automatically in a non-intrusive way for the elderly, and this is the goal of this paper. We present a general approach based on 3D cameras and neural network algorithms that offers an efficient solution for two different scenarios of telerehabilitation and telecare for elderly people. Our empirical analysis reveals the effectiveness and accuracy of the algorithms presented in our approach and provides more than promising results when the neural network parameters are properly adjusted.
A Vision-Based Approach for Building Telecare and Telerehabilitation Services
Barriga, Angela; Conejero, José M.; Hernández, Juan; Jurado, Elena; Moguel, Enrique; Sánchez-Figueroa, Fernando
2016-01-01
In the last few years, telerehabilitation and telecare have become important topics in healthcare since they enable people to remain independent in their own homes by providing person-centered technologies to support the individual. These technologies allows elderly people to be assisted in their home, instead of traveling to a clinic, providing them wellbeing and personalized health care. The literature shows a great number of interesting proposals to address telerehabilitation and telecare scenarios, which may be mainly categorized into two broad groups, namely wearable devices and context-aware systems. However, we believe that these apparently different scenarios may be addressed by a single context-aware approach, concretely a vision-based system that can operate automatically in a non-intrusive way for the elderly, and this is the goal of this paper. We present a general approach based on 3D cameras and neural network algorithms that offers an efficient solution for two different scenarios of telerehabilitation and telecare for elderly people. Our empirical analysis reveals the effectiveness and accuracy of the algorithms presented in our approach and provides more than promising results when the neural network parameters are properly adjusted. PMID:27763540
Roeder, Ingo; Herberg, Maria; Horn, Matthias
2009-04-01
Previously, we have modeled hematopoietic stem cell organization by a stochastic, single cell-based approach. Applications to different experimental systems demonstrated that this model consistently explains a broad variety of in vivo and in vitro data. A major advantage of the agent-based model (ABM) is the representation of heterogeneity within the hematopoietic stem cell population. However, this advantage comes at the price of time-consuming simulations if the systems become large. One example in this respect is the modeling of disease and treatment dynamics in patients with chronic myeloid leukemia (CML), where the realistic number of individual cells to be considered exceeds 10(6). To overcome this deficiency, without losing the representation of the inherent heterogeneity of the stem cell population, we here propose to approximate the ABM by a system of partial differential equations (PDEs). The major benefit of such an approach is its independence from the size of the system. Although this mean field approach includes a number of simplifying assumptions compared to the ABM, it retains the key structure of the model including the "age"-structure of stem cells. We show that the PDE model qualitatively and quantitatively reproduces the results of the agent-based approach.
Deep Recurrent Neural Network-Based Autoencoders for Acoustic Novelty Detection
Vesperini, Fabio; Schuller, Björn
2017-01-01
In the emerging field of acoustic novelty detection, most research efforts are devoted to probabilistic approaches such as mixture models or state-space models. Only recent studies introduced (pseudo-)generative models for acoustic novelty detection with recurrent neural networks in the form of an autoencoder. In these approaches, auditory spectral features of the next short term frame are predicted from the previous frames by means of Long-Short Term Memory recurrent denoising autoencoders. The reconstruction error between the input and the output of the autoencoder is used as activation signal to detect novel events. There is no evidence of studies focused on comparing previous efforts to automatically recognize novel events from audio signals and giving a broad and in depth evaluation of recurrent neural network-based autoencoders. The present contribution aims to consistently evaluate our recent novel approaches to fill this white spot in the literature and provide insight by extensive evaluations carried out on three databases: A3Novelty, PASCAL CHiME, and PROMETHEUS. Besides providing an extensive analysis of novel and state-of-the-art methods, the article shows how RNN-based autoencoders outperform statistical approaches up to an absolute improvement of 16.4% average F-measure over the three databases. PMID:28182121
Public nutrition in complex emergencies.
Young, Helen; Borrel, Annalies; Holland, Diane; Salama, Peter
Public nutrition is a broad-based, problem-solving approach to addressing malnutrition in complex emergencies that combines analysis of nutritional risk and vulnerability with action-oriented strategies, including policies, programmes, and capacity development. This paper focuses on six broad areas: nutritional assessment, distribution of a general food ration, prevention and treatment of moderate malnutrition, treatment of severe malnutrition in children and adults, prevention and treatment of micronutrient deficiency diseases, and nutritional support for at-risk groups, including infants, pregnant and lactating women, elderly people, and people living with HIV. Learning and documenting good practice from previous emergencies, the promotion of good practice in current emergencies, and adherence to international standards and guidelines have contributed to establishing the field of public nutrition. However, many practical challenges reduce the effectiveness of nutritional interventions in complex emergencies, and important research and programmatic questions remain.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shir, Daniel J.; Yoon, Jongseung; Chanda, Debashis
2010-08-11
Recently developed classes of monocrystalline silicon solar microcells can be assembled into modules with characteristics (i.e., mechanically flexible forms, compact concentrator designs, and high-voltage outputs) that would be impossible to achieve using conventional, wafer-based approaches. This paper presents experimental and computational studies of the optics of light absorption in ultrathin microcells that include nanoscale features of relief on their surfaces, formed by soft imprint lithography. Measurements on working devices with designs optimized for broad band trapping of incident light indicate good efficiencies in energy production even at thicknesses of just a few micrometers. These outcomes are relevant not only tomore » the microcell technology described here but also to other photovoltaic systems that benefit from thin construction and efficient materials utilization.« less
Parallel-processing with surface plasmons, a new strategy for converting the broad solar spectrum
NASA Technical Reports Server (NTRS)
Anderson, L. M.
1982-01-01
A new strategy for efficient solar-energy conversion is based on parallel processing with surface plasmons: guided electromagnetic waves supported on thin films of common metals like aluminum or silver. The approach is unique in identifying a broadband carrier with suitable range for energy transport and an inelastic tunneling process which can be used to extract more energy from the more energetic carriers without requiring different materials for each frequency band. The aim is to overcome the fundamental 56-percent loss associated with mismatch between the broad solar spectrum and the monoenergetic conduction electrons used to transport energy in conventional silicon solar cells. This paper presents a qualitative discussion of the unknowns and barrier problems, including ideas for coupling surface plasmons into the tunnels, a step which has been the weak link in the efficiency chain.
Broad phonetic class definition driven by phone confusions
NASA Astrophysics Data System (ADS)
Lopes, Carla; Perdigão, Fernando
2012-12-01
Intermediate representations between the speech signal and phones may be used to improve discrimination among phones that are often confused. These representations are usually found according to broad phonetic classes, which are defined by a phonetician. This article proposes an alternative data-driven method to generate these classes. Phone confusion information from the analysis of the output of a phone recognition system is used to find clusters at high risk of mutual confusion. A metric is defined to compute the distance between phones. The results, using TIMIT data, show that the proposed confusion-driven phone clustering method is an attractive alternative to the approaches based on human knowledge. A hierarchical classification structure to improve phone recognition is also proposed using a discriminative weight training method. Experiments show improvements in phone recognition on the TIMIT database compared to a baseline system.
NASA Astrophysics Data System (ADS)
Siontorou, Christina G.
2012-12-01
Herbal products have gained increasing popularity in the last decades, and are now broadly used to treat illness and improve health. Notwithstanding the public opinion, both, safety and efficacy, are major sources of dispute among the scientific community, mainly due to lack of (or scarcity or scattered) conclusive data linking a herbal constituent to pharmacological action in vivo, in a way that benefit overrides risk. This paper presents a methodological framework for addressing natural medicine in a systematic and holistic way with a view to providing medicinal products based on interactive chemical/herbal ingredients.
Beyond vertical integration--Community based medical education.
Kennedy, Emma Margaret
2006-11-01
The term 'vertical integration' is used broadly in medical education, sometimes when discussing community based medical education (CBME). This article examines the relevance of the term 'vertical integration' and provides an alternative perspective on the complexities of facilitating the CBME process. The principles of learner centredness, patient centredness and flexibility are fundamental to learning in the diverse contexts of 'community'. Vertical integration as a structural concept is helpful for academic organisations but has less application to education in the community setting; a different approach illuminates the strengths and challenges of CBME that need consideration by these organisations.
NASA Hydrogen Research for Spaceport and Space Based Applications
NASA Technical Reports Server (NTRS)
Anderson, Tim
2006-01-01
The activities presented are a broad based approach to advancing key hydrogen related technologies in areas such as hydrogen production, distributed sensors for hydrogen-leak detection, laser instrumentation for hydrogen-leak detection, and cryogenic transport and storage. Presented are the results form 15 research projects, education, and outreach activities, system and trade studies, and project management. The work will aid in advancing the state-of-the-art for several critical technologies related to the implementation of a hydrogen infrastructure. Activities conducted are relevant to a number of propulsion and power systems for terrestrial, aeronautics, and aerospace applications.
Localization-based super-resolution imaging of cellular structures.
Kanchanawong, Pakorn; Waterman, Clare M
2013-01-01
Fluorescence microscopy allows direct visualization of fluorescently tagged proteins within cells. However, the spatial resolution of conventional fluorescence microscopes is limited by diffraction to ~250 nm, prompting the development of super-resolution microscopy which offers resolution approaching the scale of single proteins, i.e., ~20 nm. Here, we describe protocols for single molecule localization-based super-resolution imaging, using focal adhesion proteins as an example and employing either photoswitchable fluorophores or photoactivatable fluorescent proteins. These protocols should also be easily adaptable to imaging a broad array of macromolecular assemblies in cells whose components can be fluorescently tagged and assemble into high density structures.
Federal Register 2010, 2011, 2012, 2013, 2014
2012-12-10
... Effectiveness of a Proposed Rule Change To Amend Its Rule Related to Multi-Class Broad- Based Index Option... Rule Change The Exchange proposes to amend its rule related to multi-class broad-based index option... is to (i) clarify that the term ``Multi-Class Broad-Based Index Option Spread Order (Multi-Class...
Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus
USDA-ARS?s Scientific Manuscript database
Disease pathways form overlapping networks, and hub proteins represent attractive targets for broad-spectrum drugs. Using bacterial toxins as a proof of concept, we describe a new approach of discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pa...
Klosterman, E S; Kass, P H; Walsh, D A
2009-08-01
This is the first of two papers that provide extensive data and analysis on the two major approaches to clinical veterinary education, which either provide students with experience of a broad range of species (often defined as omni/general clinical competence), or just a few species (sometimes just one), usually termed 'tracking'. Together the two papers provide a detailed analysis of these two approaches for the first time. The responsibilities of veterinary medicine and veterinary education are rapidly increasing throughoutthe globe. It is critical for all in veterinary education to reassess the approaches that have been used, and evaluate on a school-by-school basis which may best meet its expanding and ever-deepening responsibilities.
Ma, Wen; Waffo-Téguo, Pierre; Alessandra Paissoni, Maria; Jourdes, Michäel; Teissedre, Pierre-Louis
2018-05-30
Polymeric tannins from grapes have always been reported as an unresolved broad peak in HPLC chromatograms, and this has severely limited their identification to date. This study aimed to disassemble this broad peak and explore the polymeric tannin molecules inside. By applying centrifugal partition chromatography (CPC), an efficient separation approach was developed to split the broad peak of grape seed tannins into fractions. Then, the fractions were analyzed by Q-ToF (quadrupole time-of-flight mass spectrometry) to determine the corresponding structures of the tannins. The results suggest that grape seed polymeric tannins were eluted consecutively according to their degree of polymerization (DP). Condensed tannins identified in wine grape seed have a range of DP and degree of galloylation (DG) up to 20 and 11, respectively. The molecular mass of the largest molecule detected was 6067. To our knowledge, this is the first report to offer an insight into the broad peak of polymeric tannins found with HPLC and to characterize the tannins with a DP up to 20 as shown by HRMS and MS/MS data. Copyright © 2018 Elsevier Ltd. All rights reserved.
Molecular diagnostic methods for invasive fungal disease: the horizon draws nearer?
Halliday, C L; Kidd, S E; Sorrell, T C; Chen, S C-A
2015-04-01
Rapid, accurate diagnostic laboratory tests are needed to improve clinical outcomes of invasive fungal disease (IFD). Traditional direct microscopy, culture and histological techniques constitute the 'gold standard' against which newer tests are judged. Molecular diagnostic methods, whether broad-range or fungal-specific, have great potential to enhance sensitivity and speed of IFD diagnosis, but have varying specificities. The use of PCR-based assays, DNA sequencing, and other molecular methods including those incorporating proteomic approaches such as matrix-assisted laser desorption ionisation-time of flight mass spectroscopy (MALDI-TOF MS) have shown promising results. These are used mainly to complement conventional methods since they require standardisation before widespread implementation can be recommended. None are incorporated into diagnostic criteria for defining IFD. Commercial assays may assist standardisation. This review provides an update of molecular-based diagnostic approaches applicable to biological specimens and fungal cultures in microbiology laboratories. We focus on the most common pathogens, Candida and Aspergillus, and the mucormycetes. The position of molecular-based approaches in the detection of azole and echinocandin antifungal resistance is also discussed.
Development of Long-term Datasets from Satellite BUV Instruments: The "Soft" Calibration Approach
NASA Technical Reports Server (NTRS)
Bhartia, Pawan K.; Taylor, Steven; Jaross, Glen
2005-01-01
The first BUV instrument was launched in April 1970 on NASA's Nimbus4 satellite. More than a dozen instruments, broadly based on the same principle, but using very different technologies, have been launched in the last 35 years on NASA, NOAA, Japanese and European satellites. In this paper we describe the basic principles of the "soft" calibration approach that we have successfully applied to the data from many of these instruments to produce a consistent long-term record of total ozone, ozone profile and aerosols. This approach is based on using accurate radiative transfer models and assumed/known properties of the atmosphere in ultraviolet to derive calibration parameters. Although the accuracy of the results inevitably depends upon how well the assumed atmospheric properties are known, the technique has several built-in cross- checks that improve the robustness of the method. To develop further confidence in the data the soft calibration technique can be combined with data collected from few well- calibrated ground-based instruments. We will use examples from past and present BUV instruments to show how the method works.
Forecast Based Financing for Managing Weather and Climate Risks to Reduce Potential Disaster Impacts
NASA Astrophysics Data System (ADS)
Arrighi, J.
2017-12-01
There is a critical window of time to reduce potential impacts of a disaster after a forecast for heightened risk is issued and before an extreme event occurs. The concept of Forecast-based Financing focuses on this window of opportunity. Through advanced preparation during system set-up, tailored methodologies are used to 1) analyze a range of potential extreme event forecasts, 2) identify emergency preparedness measures that can be taken when factoring in forecast lead time and inherent uncertainty and 3) develop standard operating procedures that are agreed on and tied to guaranteed funding sources to facilitate emergency measures led by the Red Cross or government actors when preparedness measures are triggered. This presentation will focus on a broad overview of the current state of theory and approaches used in developing a forecast-based financing systems - with a specific focus on hydrologic events, case studies of success and challenges in various contexts where this approach is being piloted, as well as what is on the horizon to be further explored and developed from a research perspective as the application of this approach continues to expand.
Symptom-Based Controller Therapy: A New Paradigm for Asthma Management
Divekar, Rohit; Ameredes, Bill T.; Calhoun, William J.
2013-01-01
Appropriate management of persistent asthma, according to US and international guidelines, requires daily use of controller medications, most generally, inhaled corticosteroids (ICS). This approach, although effective and well established, imposes burdens of treatment and side effects onto asthma patients. A growing body of evidence suggests that patients with persistent asthma need not be managed with daily ICS, but rather can use them on an intermittent basis, occasioned by the occurrence of symptoms sufficient to warrant treatment with a rescue inhaler. Large, randomized, controlled studies, over a range of asthma severity, and in a range of ages from pediatrics to adults, suggest that in well-selected patients, a symptom based approach to administering controller therapy may produce equivalent outcomes, while reducing exposure to ICS. The concept of providing anti-inflammatory treatment to the patient, at the time inflammation is developing, is termed ‘temporal personalization’. The evidence to date suggests that symptom-based controller therapy is broadly useful in selected asthma patients, and is a management approach that could be incorporated into US and international guidelines for asthma. PMID:23904098
Analyzing Human-Landscape Interactions: Tools That Integrate
NASA Astrophysics Data System (ADS)
Zvoleff, Alex; An, Li
2014-01-01
Humans have transformed much of Earth's land surface, giving rise to loss of biodiversity, climate change, and a host of other environmental issues that are affecting human and biophysical systems in unexpected ways. To confront these problems, environmental managers must consider human and landscape systems in integrated ways. This means making use of data obtained from a broad range of methods (e.g., sensors, surveys), while taking into account new findings from the social and biophysical science literatures. New integrative methods (including data fusion, simulation modeling, and participatory approaches) have emerged in recent years to address these challenges, and to allow analysts to provide information that links qualitative and quantitative elements for policymakers. This paper brings attention to these emergent tools while providing an overview of the tools currently in use for analysis of human-landscape interactions. Analysts are now faced with a staggering array of approaches in the human-landscape literature—in an attempt to bring increased clarity to the field, we identify the relative strengths of each tool, and provide guidance to analysts on the areas to which each tool is best applied. We discuss four broad categories of tools: statistical methods (including survival analysis, multi-level modeling, and Bayesian approaches), GIS and spatial analysis methods, simulation approaches (including cellular automata, agent-based modeling, and participatory modeling), and mixed-method techniques (such as alternative futures modeling and integrated assessment). For each tool, we offer an example from the literature of its application in human-landscape research. Among these tools, participatory approaches are gaining prominence for analysts to make the broadest possible array of information available to researchers, environmental managers, and policymakers. Further development of new approaches of data fusion and integration across sites or disciplines pose an important challenge for future work in integrating human and landscape components.
Pharmacological treatment of anxiety disorders: Current treatments and future directions✩
Farach, Frank J.; Pruitt, Larry D.; Jun, Janie J.; Jerud, Alissa B.; Zoellner, Lori A.; Roy-Byrne, Peter P.
2012-01-01
Modern pharmacological treatments for anxiety disorders are safer and more tolerable than they were 30 years ago. Unfortunately, treatment efficacy and duration have not improved in most cases despite a greater understanding of the pathophysiology of anxiety. Moreover, innovative treatments have not reached the market despite billions of research dollars invested in drug development. In reviewing the literature on current treatments, we argue that evidence-based practice would benefit from better research on the causes of incomplete treatment response as well as the comparative efficacy of drug combinations and sequencing. We also survey two broad approaches to the development of innovative anxiety treatments: the continued development of drugs based on specific neuroreceptors and the pharmacological manipulation of fear-related memory. We highlight directions for future research, as neither of these approaches is ready for routine clinical use. PMID:23023162
Exploring the Solar System in the Classroom: A Hands-On Approach
NASA Technical Reports Server (NTRS)
Coombs, Cassandra R.
2000-01-01
This final report discusses the development and implementation of several educational products for K-16 teachers and students. Specifically, I received support for: (A) three K-12 Teacher workshops, Exploring the Solar System in the Classroom: A Hands-On Approach, and minimal Support to finish two computer-based tutorials. (B) Contact Light: An Interactive CD-ROM, and (C) Another Look at Taurus Littrow: An Interactive GIS Database. Each of these projects directly supports NASA's Strategic Plan to: "Involve the education community in our endeavors to inspire America's students, create learning opportunities, enlighten inquisitive minds", and, to "communicate widely the content, relevancy, and excitement of NASA's missions and discoveries to inspire and to increase understanding and the broad application of science and technology." Attachment: Appendix A. And also article: "Aristarchus plateau: as potential lunar base site."
ERIC Educational Resources Information Center
Lenhart, Volker
2018-01-01
From its very beginnings, we can discern two methodological approaches to comparative education; one broadly historical-philosophical-idiographic and another broadly empirical-positivist-nomothetic. Friedrich August Hecht's 1795-1798 "De re scholastica Anglica cum Germanica comparata" ("English and German school education…
Public Entrepreneurs and the Adoption of Broad-Based Merit Aid beyond the Southeastern United States
ERIC Educational Resources Information Center
Ingle, William Kyle; Petroff, Ruth Ann
2013-01-01
The concentration of broad-based merit aid adoption in the southeastern United States has been well noted in the literature. However, there are states that have adopted broad-based merit aid programs outside of the Southeast. Guided by multiple theoretical frameworks, including innovation diffusion theory (e.g., Gray, 1973, 1994; Rogers, 2003),…
Kildgaard, Sara; Subko, Karolina; Phillips, Emma; Goidts, Violaine; de la Cruz, Mercedes; Díaz, Caridad; Gotfredsen, Charlotte H.; Frisvad, Jens C.; Nielsen, Kristian F.; Larsen, Thomas O.
2017-01-01
A marine-derived Stilbella fimetaria fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection and high resolution mass spectrometry. This led to the discovery of several bioactive compound families with different biosynthetic origins, including pimarane-type diterpenoids and hybrid polyketide-non ribosomal peptide derived compounds. Prefractionation before bioassay screening proved to be a great aid in the dereplication process, since separate fractions displaying different bioactivities allowed a quick tentative identification of known antimicrobial compounds and of potential new analogues. A new pimarane-type diterpene, myrocin F, was discovered in trace amounts and displayed cytotoxicity towards various cancer cell lines. Further media optimization led to increased production followed by the purification and bioactivity screening of several new and known pimarane-type diterpenoids. A known broad-spectrum antifungal compound, ilicicolin H, was purified along with two new analogues, hydroxyl-ilicicolin H and ilicicolin I, and their antifungal activity was evaluated. PMID:28805711
Mahbub, Parvez; Leis, John; Macka, Mirek
2018-05-15
Modeling the propagation of light from LED sources is problematic since the emission covers a broad range of wavelengths and thus cannot be considered as monochromatic. Furthermore, the lack of directivity of such sources is also problematic. Both attributes are characteristic of LEDs. Here we propose a HITRAN ( high-resolution transmission molecular absorption database) based chemometric approach that incorporates not-perfect-monochromaticity and spatial directivity of near-infrared (NIR) LED for absorbance calculations in 1-6% methane (CH 4 ) in air, considering CH 4 as a model absorbing gas. We employed the absorbance thus calculated using HITRAN to validate the experimentally measured absorbance of CH 4 . The maximum error between the measured and calculated absorbance values were within 1%. The approach can be generalized as a chemometric calibration technique for measuring gases and gas mixtures that absorb emissions from polychromatic or not-perfect-monochromatic sources, provided the gas concentration, optical path length, as well as blank and attenuated emission spectra of the light source are incorporated into the proposed chemometric approach.
van der Eerden, M M; Vlaspolder, F; de Graaff, C S; Groot, T; Bronsveld, W; Jansen, H; Boersma, W
2005-01-01
Background: There is much controversy about the ideal approach to the management of community acquired pneumonia (CAP). Recommendations differ from a pathogen directed approach to an empirical strategy with broad spectrum antibiotics. Methods: In a prospective randomised open study performed between 1998 and 2000, a pathogen directed treatment (PDT) approach was compared with an empirical broad spectrum antibiotic treatment (EAT) strategy according to the ATS guidelines of 1993 in 262 hospitalised patients with CAP. Clinical efficacy was primarily determined by the length of hospital stay (LOS). Secondary outcome parameters for clinical efficacy were assessment of therapeutic failure on antibiotics, 30 day mortality, duration of antibiotic treatment, resolution of fever, side effects, and quality of life. Results: Three hundred and three patients were enrolled in the study; 41 were excluded, leaving 262 with results available for analysis. No significant differences were found between the two treatment groups in LOS, 30 day mortality, clinical failure, or resolution of fever. Side effects, although they did not have a significant influence on the outcome parameters, occurred more frequently in patients in the EAT group than in those in the PDT group (60% v 17%, 95% CI –0.5 to –0.3; p<0.001). Conclusions: An EAT strategy with broad spectrum antibiotics for the management of hospitalised patients with CAP has comparable clinical efficacy to a PDT approach. PMID:16061709
Choi, Jeeyae; Bakken, Suzanne; Lussier, Yves A; Mendonça, Eneida A
2006-01-01
Medical logic modules are a procedural representation for sharing task-specific knowledge for decision support systems. Based on the premise that clinicians may perceive object-oriented expressions as easier to read than procedural rules in Arden Syntax-based medical logic modules, we developed a method for improving the readability of medical logic modules. Two approaches were applied: exploiting the concept-oriented features of the Medical Entities Dictionary and building an executable Java program to replace Arden Syntax procedural expressions. The usability evaluation showed that 66% of participants successfully mapped all Arden Syntax rules to Java methods. These findings suggest that these approaches can play an essential role in the creation of human readable medical logic modules and can potentially increase the number of clinical experts who are able to participate in the creation of medical logic modules. Although our approaches are broadly applicable, we specifically discuss the relevance to concept-oriented nursing terminologies and automated processing of task-specific nursing knowledge.
Why psychopathy matters: Implications for public health and violence prevention✩
Reidy, Dennis E.; Kearns, Megan C.; DeGue, Sarah; Lilienfeld, Scott O.; Massetti, Greta; Kiehl, Kent A.
2018-01-01
Psychopathy is an early-appearing risk factor for severe and chronic violence. The violence largely attributable to psychopathy constitutes a substantial portion of the societal burden to the public health and criminal justice systems, and thus necessitates significant attention from prevention experts. Yet, despite a vast base of research in psychology and criminology, the public health approach to violence has generally neglected to consider this key variable. Fundamentally, the public health approach to violence prevention is focused on achieving change at the population level to provide the most benefit to the maximum number of people. Increasing attention to the individual-level factor of psychopathy in public health could improve our ability to reduce violence at the community and societal levels. We conclude that the research literature on psychopathy points to a pressing need for a broad-based public health approach with a focus on primary prevention. Further, we consider how measuring psychopathy in public health research may benefit violence prevention, and ultimately society, in general. PMID:29593448
Clinical risk management approach for long-duration space missions.
Gray, Gary W; Sargsyan, Ashot E; Davis, Jeffrey R
2010-12-01
In the process of crewmember evaluation and certification for long-duration orbital missions, the International Space Station (ISS) Multilateral Space Medicine Board (MSMB) encounters a surprisingly wide spectrum of clinical problems. Some of these conditions are identified within the ISS Medical Standards as requiring special consideration, or as falling outside the consensus Medical Standards promulgated for the ISS program. To assess the suitability for long-duration missions on ISS for individuals with medical problems that fall outside of standards or are otherwise of significant concern, the MSMB has developed a risk matrix approach to assess the risks to the individual, the mission, and the program. The goal of this risk assessment is to provide a more objective, evidence- and risk-based approach for aeromedical disposition. Using a 4 x 4 risk matrix, the probability of an event is plotted against the potential impact. Event probability is derived from a detailed review of clinical and aerospace literature, and based on the best available evidence. The event impact (consequences) is assessed and assigned within the matrix. The result has been a refinement of MSMB case assessment based on evidence-based data incorporated into a risk stratification process. This has encouraged an objective assessment of risk and, in some cases, has resulted in recertification of crewmembers with medical conditions which hitherto would likely have been disqualifying. This paper describes a risk matrix approach developed for MSMB disposition decisions. Such an approach promotes objective, evidence-based decision-making and is broadly applicable within the aerospace medicine community.
Saliendo del circulo vicioso: Gestiones alternativas para garantizar la sostenibilidad de la pesca
Angeler, D.G.; Pope, K.L.; Allen, Craig R.
2012-01-01
The management of fisheries has historically focused on maintaining maximum sustained yields of single species. This approach generally ignored the broader social-ecological context that consists of coupled systems of people and nature, and resulted in the overexploitation of many fisheries globally, including many in Latin America. There are severe negative repercussion of overfishing, on both ecosystems and humans that rely on food and income provided by fisheries. Traditional management schemes based on maximizing should be replaced with approaches that explicitly recognize the coupling of social and ecological systems. We suggest a resilience approach that focuses on tradeoffs as a means of guaranteeing outputs over a broad range of conditions and avoiding undesirable thresholds. Resilience approaches may on average produce lower annual yields, but are more likely to allow the continued provision of multiple goods and services. A resilience approach requires scientifically derived data and consistent monitoring, and will not be successful if feedbacks between ecosystems and humans are ignored. The words "Fisheries" and "Sustainability" do not comprise an oxymoron but a logical partnership in resilience management. People and institutions engaged in Latin-American fisheries management have an opportunity to lead in the development of sustainable fisheries management with a resilience-based approach. Here we describe such an approach, and the steps necessary to ensure success.
A 21st century approach to assessing the protection of workers' health.
Rosskam, Ellen
2011-01-01
This article presents a rights-based approach to the way occupational health and safety is understood, departing from medical, engineering, and technocratic approaches that dominated the field throughout the 20th century. Moving toward a 21st century concept of the good society - based on citizenship rights and principles of universalism - a social protection-based system of assessing governments' performance in protecting workers' health and well-being is proffered. A Work Security Index (WSI) is used as a benchmarking system for evaluating national or local level governments' performance in this domain. Data from 95 countries in all regions of the world were used. A pioneering tool the WSI grouped and ranked countries based on governments' protection of workers' health and safety. Data represent findings from 95 national governments, as well as workers and employers. Among 95 countries, most have much work to do to provide the minimum measures to protect their working populations. Results reveal that women workers face particular social and economic insecurities and inequalities. We attempt to inform a broad audience about the WSI, how it can be used at multiple levels in any country for the protection of workers' health, safety, and well-being, and the need to do so.
NASA Astrophysics Data System (ADS)
Villanueva Perez, Carlos Hernan
Computational design optimization provides designers with automated techniques to develop novel and non-intuitive optimal designs. Topology optimization is a design optimization technique that allows for the evolution of a broad variety of geometries in the optimization process. Traditional density-based topology optimization methods often lack a sufficient resolution of the geometry and physical response, which prevents direct use of the optimized design in manufacturing and the accurate modeling of the physical response of boundary conditions. The goal of this thesis is to introduce a unified topology optimization framework that uses the Level Set Method (LSM) to describe the design geometry and the eXtended Finite Element Method (XFEM) to solve the governing equations and measure the performance of the design. The methodology is presented as an alternative to density-based optimization approaches, and is able to accommodate a broad range of engineering design problems. The framework presents state-of-the-art methods for immersed boundary techniques to stabilize the systems of equations and enforce the boundary conditions, and is studied with applications in 2D and 3D linear elastic structures, incompressible flow, and energy and species transport problems to test the robustness and the characteristics of the method. A comparison of the framework against density-based topology optimization approaches is studied with regards to convergence, performance, and the capability to manufacture the designs. Furthermore, the ability to control the shape of the design to operate within manufacturing constraints is developed and studied. The analysis capability of the framework is validated quantitatively through comparison against previous benchmark studies, and qualitatively through its application to topology optimization problems. The design optimization problems converge to intuitive designs and resembled well the results from previous 2D or density-based studies.
NASA Astrophysics Data System (ADS)
Mert, A.
2016-12-01
The main motivation of this study is the impending occurrence of a catastrophic earthquake along the Prince Island Fault (PIF) in Marmara Sea and the disaster risk around Marmara region, especially in İstanbul. This study provides the results of a physically-based Probabilistic Seismic Hazard Analysis (PSHA) methodology, using broad-band strong ground motion simulations, for sites within the Marmara region, Turkey, due to possible large earthquakes throughout the PIF segments in the Marmara Sea. The methodology is called physically-based because it depends on the physical processes of earthquake rupture and wave propagation to simulate earthquake ground motion time histories. We include the effects of all considerable magnitude earthquakes. To generate the high frequency (0.5-20 Hz) part of the broadband earthquake simulation, the real small magnitude earthquakes recorded by local seismic array are used as an Empirical Green's Functions (EGF). For the frequencies below 0.5 Hz the simulations are obtained using by Synthetic Green's Functions (SGF) which are synthetic seismograms calculated by an explicit 2D/3D elastic finite difference wave propagation routine. Using by a range of rupture scenarios for all considerable magnitude earthquakes throughout the PIF segments we provide a hazard calculation for frequencies 0.1-20 Hz. Physically based PSHA used here follows the same procedure of conventional PSHA except that conventional PSHA utilizes point sources or a series of point sources to represent earthquakes and this approach utilizes full rupture of earthquakes along faults. Further, conventional PSHA predicts ground-motion parameters using by empirical attenuation relationships, whereas this approach calculates synthetic seismograms for all magnitude earthquakes to obtain ground-motion parameters. PSHA results are produced for 2%, 10% and 50% hazards for all studied sites in Marmara Region.
Positional cloning in maize (Zea mays subsp. mays, Poaceae)1
Gallavotti, Andrea; Whipple, Clinton J.
2015-01-01
• Premise of the study: Positional (or map-based) cloning is a common approach to identify the molecular lesions causing mutant phenotypes. Despite its large and complex genome, positional cloning has been recently shown to be feasible in maize, opening up a diverse collection of mutants to molecular characterization. • Methods and Results: Here we outline a general protocol for positional cloning in maize. While the general strategy is similar to that used in other plant species, we focus on the unique resources and approaches that should be considered when applied to maize mutants. • Conclusions: Positional cloning approaches are appropriate for maize mutants and quantitative traits, opening up to molecular characterization the large array of genetic diversity in this agronomically important species. The cloning approach described should be broadly applicable to other species as more plant genomes become available. PMID:25606355
Do we need sustainability as a new approach in human factors and ergonomics?
Zink, Klaus J; Fischer, Klaus
2013-01-01
The International Ergonomics Association Technical Committee 'Human Factors and Sustainable Development' was established to contribute to a broad discourse about opportunities and risks resulting from current societal 'mega-trends' and their impacts on the interactions among humans and other elements of a system, e.g. in work systems. This paper focuses on the underlying key issues: how do the sustainability paradigm and human factors/ergonomics interplay and interact, and is sustainability necessary as a new approach for our discipline? Based on a discussion of the sustainability concept, some general principles for designing new and enhancing existent approaches of human factors and ergonomics regarding their orientation towards sustainability are proposed. The increasing profile of sustainability on the international stage presents new opportunities for human factors/ergonomics. Positioning of the sustainability paradigm within human factors/ergonomics is discussed. Approaches to incorporating sustainability in the design of work systems are considered.
Uniyal, Shivani; Sharma, Rajesh Kumar
2018-09-30
Chlorpyrifos (CP), an organophosphate insecticide is broadly used in the agricultural and industrial sectors to control a broad-spectrum of insects of economically important crops. CP detection has been gaining prominence due to its widespread contamination in different environmental matrices, high acute toxicity, and potential to cause long-term environmental and ecological damage even at trace levels. Traditional chromatographic methods for CP detection are complex and require sample preparation and highly skilled personnel for their operation. Over the past decades, electrochemical biosensors have emerged as a promising technology for CP detection as these circumvent deficiencies associated with classical chromatographic techniques. The advantageous features such as appreciable detection limit, miniaturization, sensitivity, low-cost and onsite detection potential are the propulsive force towards sustainable growth of electrochemical biosensing platforms. Recent development in enzyme immobilization methods, novel surface modifications, nanotechnology and fabrication techniques signify a foremost possibility for the design of electrochemical biosensing platforms with improved sensitivity and selectivity. The prime objective of this review is to accentuate the recent advances in the design of biosensing platforms based on diverse biomolecules and biomimetic molecules with unique properties, which would potentially fascinate their applicability for detection of CP residues in real samples. The review also covers the sensing principle of the prime biomolecule and biomimetic molecule based electrochemical biosensors along with their analytical performance, advantages and shortcomings. Present challenges and future outlooks in the field of electrochemical biosensors based CP detection are also discussed. This deep analysis of electrochemical biosensors will provide research directions for further approaching towards commercial development of the broad range of organophosphorus compounds. Copyright © 2018 Elsevier B.V. All rights reserved.
The Impact of Project-Based Climate Change Learning Experiences on Students' Broad Climate Literacy
NASA Astrophysics Data System (ADS)
DeWaters, J.; Powers, S. E.; Dhaniyala, S.
2014-12-01
Evidence-based pedagogical approaches such as project- and inquiry-based techniques have been shown to promote effective learning in science and engineering. The impact of project-based learning experiences on middle school (MS), high school (HS), and undergraduate (UG) students' climate literacy was investigated as part of a NASA Innovations in Climate Education (NICE) project. Project-based modules were developed and taught by MS and HS teachers who participated in climate change education workshops. UG students enrolled in a climate science course completed independent research projects that provided the basis for several of the HS/MS modules. All modules required students to acquire and analyze historical temperature data and future climate predictions, and apply their analysis to the solution of a societal or environmental problem related to our changing climate. Three versions of a quantitative survey were developed and used in a pre-test/post-test research design to help evaluate the project's impact on MS, HS, and UG students' climate literacy, which includes broad climate knowledge as well as affective and behavioral aspects. Content objectives were guided primarily by the 2009 document, Climate Literacy: The Essential Principles of Climate Sciences. All three groups of students made modest but statistically significant cognitive (p<<0.001) and affective (p<0.01) gains; UG students also showed an increase in behavior scores (p=0.001). Results of an ANCOVA showed significant differences in students' cognitive (p<0.001), behavioral (p=0.005) and self-efficacy (p=0.012) outcomes among the 9 participating MS and HS classrooms, where both teacher and module content varied. The presentation will include a description of some key aspects of the project-based curricula developed and used in this research, the development and content of the climate literacy survey, and the interpretation of specific pre/post changes in participating students relative to the content of and approach used in the project-based modules.
Multi-Layer Approach for the Detection of Selective Forwarding Attacks
Alajmi, Naser; Elleithy, Khaled
2015-01-01
Security breaches are a major threat in wireless sensor networks (WSNs). WSNs are increasingly used due to their broad range of important applications in both military and civilian domains. WSNs are prone to several types of security attacks. Sensor nodes have limited capacities and are often deployed in dangerous locations; therefore, they are vulnerable to different types of attacks, including wormhole, sinkhole, and selective forwarding attacks. Security attacks are classified as data traffic and routing attacks. These security attacks could affect the most significant applications of WSNs, namely, military surveillance, traffic monitoring, and healthcare. Therefore, there are different approaches to detecting security attacks on the network layer in WSNs. Reliability, energy efficiency, and scalability are strong constraints on sensor nodes that affect the security of WSNs. Because sensor nodes have limited capabilities in most of these areas, selective forwarding attacks cannot be easily detected in networks. In this paper, we propose an approach to selective forwarding detection (SFD). The approach has three layers: MAC pool IDs, rule-based processing, and anomaly detection. It maintains the safety of data transmission between a source node and base station while detecting selective forwarding attacks. Furthermore, the approach is reliable, energy efficient, and scalable. PMID:26610499
Multi-Layer Approach for the Detection of Selective Forwarding Attacks.
Alajmi, Naser; Elleithy, Khaled
2015-11-19
Security breaches are a major threat in wireless sensor networks (WSNs). WSNs are increasingly used due to their broad range of important applications in both military and civilian domains. WSNs are prone to several types of security attacks. Sensor nodes have limited capacities and are often deployed in dangerous locations; therefore, they are vulnerable to different types of attacks, including wormhole, sinkhole, and selective forwarding attacks. Security attacks are classified as data traffic and routing attacks. These security attacks could affect the most significant applications of WSNs, namely, military surveillance, traffic monitoring, and healthcare. Therefore, there are different approaches to detecting security attacks on the network layer in WSNs. Reliability, energy efficiency, and scalability are strong constraints on sensor nodes that affect the security of WSNs. Because sensor nodes have limited capabilities in most of these areas, selective forwarding attacks cannot be easily detected in networks. In this paper, we propose an approach to selective forwarding detection (SFD). The approach has three layers: MAC pool IDs, rule-based processing, and anomaly detection. It maintains the safety of data transmission between a source node and base station while detecting selective forwarding attacks. Furthermore, the approach is reliable, energy efficient, and scalable.
A Robust Sound Source Localization Approach for Microphone Array with Model Errors
NASA Astrophysics Data System (ADS)
Xiao, Hua; Shao, Huai-Zong; Peng, Qi-Cong
In this paper, a robust sound source localization approach is proposed. The approach retains good performance even when model errors exist. Compared with previous work in this field, the contributions of this paper are as follows. First, an improved broad-band and near-field array model is proposed. It takes array gain, phase perturbations into account and is based on the actual positions of the elements. It can be used in arbitrary planar geometry arrays. Second, a subspace model errors estimation algorithm and a Weighted 2-Dimension Multiple Signal Classification (W2D-MUSIC) algorithm are proposed. The subspace model errors estimation algorithm estimates unknown parameters of the array model, i. e., gain, phase perturbations, and positions of the elements, with high accuracy. The performance of this algorithm is improved with the increasing of SNR or number of snapshots. The W2D-MUSIC algorithm based on the improved array model is implemented to locate sound sources. These two algorithms compose the robust sound source approach. The more accurate steering vectors can be provided for further processing such as adaptive beamforming algorithm. Numerical examples confirm effectiveness of this proposed approach.
Self-Brown, Shannon; Lai, Betty; Patterson, Alexandria; Glasheen, Theresa
2017-08-01
This paper reviews youth outcomes following exposure to natural disaster, with a focus on three relatively understudied outcomes: externalizing behavior problems, physical health, and posttraumatic growth. Recent, high-impact studies focusing on each outcome are summarized. Studies highlighted in this review utilize innovative and comprehensive approaches to improve our current understanding of youth broad-based physical and mental health outcomes beyond PTSD. The review concludes with recommendations to advance the field of youth disaster research by exploring how disasters may impact children across multiple domains, as well as using cutting edge ecobiological approaches and advanced modeling strategies to better understand how youth adjust and thrive following natural disaster.
Microresonator soliton dual-comb spectroscopy
NASA Astrophysics Data System (ADS)
Suh, Myoung-Gyun; Yang, Qi-Fan; Yang, Ki Youl; Yi, Xu; Vahala, Kerry J.
2016-11-01
Measurement of optical and vibrational spectra with high resolution provides a way to identify chemical species in cluttered environments and is of general importance in many fields. Dual-comb spectroscopy has emerged as a powerful approach for acquiring nearly instantaneous Raman and optical spectra with unprecedented resolution. Spectra are generated directly in the electrical domain, without the need for bulky mechanical spectrometers. We demonstrate a miniature soliton-based dual-comb system that can potentially transfer the approach to a chip platform. These devices achieve high-coherence pulsed mode locking. They also feature broad, reproducible spectral envelopes, an essential feature for dual-comb spectroscopy. Our work shows the potential for integrated spectroscopy with high signal-to-noise ratios and fast acquisition rates.
Use of Multiscale Entropy to Facilitate Artifact Detection in Electroencephalographic Signals
Mariani, Sara; Borges, Ana F. T.; Henriques, Teresa; Goldberger, Ary L.; Costa, Madalena D.
2016-01-01
Electroencephalographic (EEG) signals present a myriad of challenges to analysis, beginning with the detection of artifacts. Prior approaches to noise detection have utilized multiple techniques, including visual methods, independent component analysis and wavelets. However, no single method is broadly accepted, inviting alternative ways to address this problem. Here, we introduce a novel approach based on a statistical physics method, multiscale entropy (MSE) analysis, which quantifies the complexity of a signal. We postulate that noise corrupted EEG signals have lower information content, and, therefore, reduced complexity compared with their noise free counterparts. We test the new method on an open-access database of EEG signals with and without added artifacts due to electrode motion. PMID:26738116
Khodakov, Dmitriy; Wang, Chunyan; Zhang, David Yu
2016-10-01
Nucleic acid sequence variations have been implicated in many diseases, and reliable detection and quantitation of DNA/RNA biomarkers can inform effective therapeutic action, enabling precision medicine. Nucleic acid analysis technologies being translated into the clinic can broadly be classified into hybridization, PCR, and sequencing, as well as their combinations. Here we review the molecular mechanisms of popular commercial assays, and their progress in translation into in vitro diagnostics. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Machine Learning in Intrusion Detection
2005-07-01
machine learning tasks. Anomaly detection provides the core technology for a broad spectrum of security-centric applications. In this dissertation, we examine various aspects of anomaly based intrusion detection in computer security. First, we present a new approach to learn program behavior for intrusion detection. Text categorization techniques are adopted to convert each process to a vector and calculate the similarity between two program activities. Then the k-nearest neighbor classifier is employed to classify program behavior as normal or intrusive. We demonstrate
An Emerging New Risk Analysis Science: Foundations and Implications.
Aven, Terje
2018-05-01
To solve real-life problems-such as those related to technology, health, security, or climate change-and make suitable decisions, risk is nearly always a main issue. Different types of sciences are often supporting the work, for example, statistics, natural sciences, and social sciences. Risk analysis approaches and methods are also commonly used, but risk analysis is not broadly accepted as a science in itself. A key problem is the lack of explanatory power and large uncertainties when assessing risk. This article presents an emerging new risk analysis science based on novel ideas and theories on risk analysis developed in recent years by the risk analysis community. It builds on a fundamental change in thinking, from the search for accurate predictions and risk estimates, to knowledge generation related to concepts, theories, frameworks, approaches, principles, methods, and models to understand, assess, characterize, communicate, and (in a broad sense) manage risk. Examples are used to illustrate the importance of this distinct/separate risk analysis science for solving risk problems, supporting science in general and other disciplines in particular. © 2017 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.
Vaccine approaches conferring cross-protection against influenza viruses
Vemula, Sai V.; Sayedahmed, Ekramy E; Sambhara, Suryaprakash; Mittal, Suresh K.
2018-01-01
Introduction Annual vaccination is one of the most efficient and cost-effective strategies to prevent and control influenza epidemics. Most of currently available influenza vaccines are strong inducer of antibody responses against viral surface proteins, hemagglutinin (HA) and neuraminidase (NA), but are poor inducers of cell-mediated immune responses against conserved internal proteins. Moreover, due to the high variability of viral surface proteins because of antigenic drift or antigenic shift, many of the currently licensed vaccines confer little or no protection against drift or shift variants. Areas covered Next generation influenza vaccines that can induce humoral immune responses to receptor-binding epitopes as well as broadly neutralizing conserved epitopes, and cell-mediated immune responses against highly conserved internal proteins would be effective against variant viruses as well as a novel pandemic influenza until circulating strain-specific vaccines become available. Here we discuss vaccine approaches that have potential to provide broad spectrum protection against influenza viruses. Expert opinion Based on current progress in defining cross-protective influenza immunity, it seems that the development of a universal influenza vaccine is feasible. It would revolutionize the strategy for influenza pandemic preparedness, and significantly impact the shelf-life and protection efficacy of seasonal influenza vaccines. PMID:28925296
Using community archetypes to better understand differential community adaptation to wildfire risk
Carroll, Matthew; Paveglio, Travis
2016-01-01
One of the immediate challenges of wildfire management concerns threats to human safety and property in residential areas adjacent to non-cultivated vegetation. One approach for relieving this problem is to increase human community ‘adaptiveness’ to deal with the risk and reality of fire in a variety of landscapes. The challenge in creating ‘fire-adapted communities’ (FACs) is the great diversity in character and make-up of populations at risk from wildfire. This paper outlines a recently developed categorization scheme for Wildland–Urban Interface (WUI) communities based on a larger conceptual approach for understanding how social diversity is likely to influence the creation of FACs. The WUI categorization scheme situates four community archetypes on a continuum that recognizes dynamic change in human community functioning. We use results from the WUI classification scheme to outline key characteristics associated with each archetype and results from recent case studies to demonstrate the diversity across WUI communities. Differences among key characteristics of local social context will likely result in the need for different adaptation strategies to wildfire. While the WUI archetypes described here may not be broadly applicable to other parts of the world, we argue that the conceptual approach and strategies for systematically documenting local influences on wildfire adaptation have potential for broad application. This article is part of the themed issue ‘The interaction of fire and mankind’. PMID:27216514
Using community archetypes to better understand differential community adaptation to wildfire risk.
Carroll, Matthew; Paveglio, Travis
2016-06-05
One of the immediate challenges of wildfire management concerns threats to human safety and property in residential areas adjacent to non-cultivated vegetation. One approach for relieving this problem is to increase human community 'adaptiveness' to deal with the risk and reality of fire in a variety of landscapes. The challenge in creating 'fire-adapted communities' (FACs) is the great diversity in character and make-up of populations at risk from wildfire. This paper outlines a recently developed categorization scheme for Wildland-Urban Interface (WUI) communities based on a larger conceptual approach for understanding how social diversity is likely to influence the creation of FACs. The WUI categorization scheme situates four community archetypes on a continuum that recognizes dynamic change in human community functioning. We use results from the WUI classification scheme to outline key characteristics associated with each archetype and results from recent case studies to demonstrate the diversity across WUI communities. Differences among key characteristics of local social context will likely result in the need for different adaptation strategies to wildfire. While the WUI archetypes described here may not be broadly applicable to other parts of the world, we argue that the conceptual approach and strategies for systematically documenting local influences on wildfire adaptation have potential for broad application.This article is part of the themed issue 'The interaction of fire and mankind'. © 2016 The Author(s).
Monolithically Integrated Mid-Infrared Quantum Cascade Laser and Detector
Schwarz, Benedikt; Reininger, Peter; Detz, Hermann; Zederbauer, Tobias; Andrews, Aaron Maxwell; Schrenk, Werner; Strasser, Gottfried
2013-01-01
We demonstrate the monolithic integration of a mid-infrared laser and detector utilizing a bi-functional quantum cascade active region. When biased, this active region provides optical gain, while it can be used as a detector at zero bias. With our novel approach we can measure the light intensity of the laser on the same chip without the need of external lenses or detectors. Based on a bound-to-continuum design, the bi-functional active region has an inherent broad electro-luminescence spectrum of 200 cm−1, which indicate sits use for single mode laser arrays. We have measured a peak signal of 191.5 mV at theon-chip detector, without any amplification. The room-temperature pulsed emission with an averaged power consumption of 4 mW and the high-speed detection makes these devices ideal for low-power sensors. The combination of the on-chip detection functionality, the broad emission spectrum and the low average power consumption indicates the potential of our bi-functional quantum cascade structures to build a mid-infrared lab-on-a-chip based on quantum cascade laser technology. PMID:23389348
A Research Framework for Reducing Preventable Patient Harm
Weinstein, Robert; Cardo, Denise M.; Goeschel, Christine A.; Berenholtz, Sean M.; Saint, Sanjay; Jernigan, John A.
2011-01-01
Programs to reduce central line–associated bloodstream infections (CLABSIs) have improved the safety of hospitalized patients. Efforts are underway to disseminate these successes broadly to reduce other types of hospital-acquired infectious and noninfectious preventable harms. Unfortunately, the ability to broadly measure and prevent other types of preventable harms, especially infectious harms, needs enhancement. Moreover, an overarching research framework for creating and integrating evidence will help expedite the development of national prevention programs. This article outlines a 5-phase translational (T) framework to develop robust research programs that reduce preventable harm, as follows: phase T0, discover opportunities and approaches to prevent adverse health care events; phase T1, use T0 discoveries to develop and test interventions on a small scale; phase T2, broaden and strengthen the evidence base for promising interventions to develop evidence-based guidelines; phase T3, translate guidelines into clinical practice; and phase T4, implement and evaluate T3 work on a national and international scale. Policy makers should use this framework to fill in the knowledge gaps, coordinate efforts among federal agencies, and prioritize research funding. PMID:21258104
Composite Supraparticles with Tunable Light Emission
2017-01-01
Robust luminophores emitting light with broadly tunable colors are desirable in many applications such as light-emitting diode (LED)-based lighting, displays, integrated optoelectronics and biology. Nanocrystalline quantum dots with multicolor emission, from core- and shell-localized excitons, as well as solid layers of mixed quantum dots that emit different colors have been proposed. Here, we report on colloidal supraparticles that are composed of three types of Cd(Se,ZnS) core/(Cd,Zn)S shell nanocrystals with emission in the red, green, and blue. The emission of the supraparticles can be varied from pure to composite colors over the entire visible region and fine-tuned into variable shades of white light by mixing the nanocrystals in controlled proportions. Our approach results in supraparticles with sizes spanning the colloidal domain and beyond that combine versatility and processability with a broad, stable, and tunable emission, promising applications in lighting devices and biological research. PMID:28787121
Synthesis of many different types of organic small molecules using one automated process.
Li, Junqi; Ballmer, Steven G; Gillis, Eric P; Fujii, Seiko; Schmidt, Michael J; Palazzolo, Andrea M E; Lehmann, Jonathan W; Morehouse, Greg F; Burke, Martin D
2015-03-13
Small-molecule synthesis usually relies on procedures that are highly customized for each target. A broadly applicable automated process could greatly increase the accessibility of this class of compounds to enable investigations of their practical potential. Here we report the synthesis of 14 distinct classes of small molecules using the same fully automated process. This was achieved by strategically expanding the scope of a building block-based synthesis platform to include even C(sp3)-rich polycyclic natural product frameworks and discovering a catch-and-release chromatographic purification protocol applicable to all of the corresponding intermediates. With thousands of compatible building blocks already commercially available, many small molecules are now accessible with this platform. More broadly, these findings illuminate an actionable roadmap to a more general and automated approach for small-molecule synthesis. Copyright © 2015, American Association for the Advancement of Science.
Subwavelength grating enabled on-chip ultra-compact optical true time delay line
Wang, Junjia; Ashrafi, Reza; Adams, Rhys; Glesk, Ivan; Gasulla, Ivana; Capmany, José; Chen, Lawrence R.
2016-01-01
An optical true time delay line (OTTDL) is a basic photonic building block that enables many microwave photonic and optical processing operations. The conventional design for an integrated OTTDL that is based on spatial diversity uses a length-variable waveguide array to create the optical time delays, which can introduce complexities in the integrated circuit design. Here we report the first ever demonstration of an integrated index-variable OTTDL that exploits spatial diversity in an equal length waveguide array. The approach uses subwavelength grating waveguides in silicon-on-insulator (SOI), which enables the realization of OTTDLs having a simple geometry and that occupy a compact chip area. Moreover, compared to conventional wavelength-variable delay lines with a few THz operation bandwidth, our index-variable OTTDL has an extremely broad operation bandwidth practically exceeding several tens of THz, which supports operation for various input optical signals with broad ranges of central wavelength and bandwidth. PMID:27457024
Mass Spectrometry on Future Mars Landers
NASA Technical Reports Server (NTRS)
Brinckerhoff, W. B.; Mahaffy, P. R.
2011-01-01
Mass spectrometry investigations on the 2011 Mars Science Laboratory (MSL) and the 2018 ExoMars missions will address core science objectives related to the potential habitability of their landing site environments and more generally the near-surface organic inventory of Mars. The analysis of complex solid samples by mass spectrometry is a well-known approach that can provide a broad and sensitive survey of organic and inorganic compounds as well as supportive data for mineralogical analysis. The science value of such compositional information is maximized when one appreciates the particular opportunities and limitations of in situ analysis with resource-constrained instrumentation in the context of a complete science payload and applied to materials found in a particular environment. The Sample Analysis at Mars (SAM) investigation on MSL and the Mars Organic Molecule Analyzer (MOMA) investigation on ExoMars will thus benefit from and inform broad-based analog field site work linked to the Mars environments where such analysis will occur.
Subwavelength grating enabled on-chip ultra-compact optical true time delay line.
Wang, Junjia; Ashrafi, Reza; Adams, Rhys; Glesk, Ivan; Gasulla, Ivana; Capmany, José; Chen, Lawrence R
2016-07-26
An optical true time delay line (OTTDL) is a basic photonic building block that enables many microwave photonic and optical processing operations. The conventional design for an integrated OTTDL that is based on spatial diversity uses a length-variable waveguide array to create the optical time delays, which can introduce complexities in the integrated circuit design. Here we report the first ever demonstration of an integrated index-variable OTTDL that exploits spatial diversity in an equal length waveguide array. The approach uses subwavelength grating waveguides in silicon-on-insulator (SOI), which enables the realization of OTTDLs having a simple geometry and that occupy a compact chip area. Moreover, compared to conventional wavelength-variable delay lines with a few THz operation bandwidth, our index-variable OTTDL has an extremely broad operation bandwidth practically exceeding several tens of THz, which supports operation for various input optical signals with broad ranges of central wavelength and bandwidth.
Saboo, Sugandha; Tumban, Ebenezer; Peabody, Julianne; Wafula, Denis; Peabody, David S.; Chackerian, Bryce; Muttil, Pavan
2016-01-01
Existing vaccines against human papillomavirus (HPV) require continuous cold-chain storage. Previously, we developed a bacteriophage virus-like particle (VLP) based vaccine for Human Papillomavirus (HPV) infection, which elicits broadly neutralizing antibodies against diverse HPV types. Here, we formulated these VLPs into a thermostable dry powder using a multi-component excipient system and by optimizing the spray drying parameters using a half-factorial design approach. Dry powder VLPs were stable after spray drying and after long-term storage at elevated temperatures. Immunization of mice with a single dose of reconstituted dry powder VLPs that were stored at 37°C for more than a year elicited high anti-L2 IgG antibody titers. Spray dried thermostable, broadly protective L2 bacteriophage VLPs vaccine could be accessible to remote regions of the world (where ~84% of cervical cancer patients reside) by eliminating the cold-chain requirement during transportation and storage. PMID:27019231
Sample stream distortion modeled in continuous-flow electrophoresis
NASA Technical Reports Server (NTRS)
Rhodes, P. H.
1979-01-01
Buoyancy-induced disturbances in an electrophoresis-type chamber were investigated. Five tracer streams (latex) were used to visualize the flows while a nine-thermistor array sensed the temperature field. The internal heating to the chamber was provided by a 400 Hz electrical field. Cooling to the chamber was provided on the front and back faces and, in addition, on both chamber side walls. Disturbances to the symmetric base flow in the chamber occurred in the broad plane of the chamber and resulted from the formation of lateral and axial temperature gradients. The effect of these gradients was to retard or increase local flow velocities at different positions in the chamber cross section, which resulted in lateral secondary flows being induced in the broad plane of the chamber. As the adverse temperature gradients increased in magnitude, the critical Rayleigh number was approached and reverse (separated) flow became apparent, which, subsequently, led to the onset of time variant secondary flows.
Assessment Practices of Child Clinicians.
Cook, Jonathan R; Hausman, Estee M; Jensen-Doss, Amanda; Hawley, Kristin M
2017-03-01
Assessment is an integral component of treatment. However, prior surveys indicate clinicians may not use standardized assessment strategies. We surveyed 1,510 clinicians and used multivariate analysis of variance to explore group differences in specific measure use. Clinicians used unstandardized measures more frequently than standardized measures, although psychologists used standardized measures more frequently than nonpsychologists. We also used latent profile analysis to classify clinicians based on their overall approach to assessment and examined associations between clinician-level variables and assessment class or profile membership. A four-profile model best fit the data. The largest profile consisted of clinicians who primarily used unstandardized assessments (76.7%), followed by broad-spectrum assessors who regularly use both standardized and unstandardized assessment (11.9%), and two smaller profiles of minimal (6.0%) and selective assessors (5.5%). Compared with broad-spectrum assessors, unstandardized and minimal assessors were less likely to report having adequate standardized measures training. Implications for clinical practice and training are discussed.
17 CFR 41.14 - Transition period for indexes that cease being narrow-based security indexes.
Code of Federal Regulations, 2014 CFR
2014-04-01
... day tolerance provision. An index that is a narrow-based security index that becomes a broad-based... than forty-five days. An index that is a narrow-based security index that becomes a broad-based...
A New Approach to Produce HIV-1 Envelope Trimers
AlSalmi, Wadad; Mahalingam, Marthandan; Ananthaswamy, Neeti; Hamlin, Christopher; Flores, Dalia; Gao, Guofen; Rao, Venigalla B.
2015-01-01
The trimeric envelope spike of HIV-1 mediates virus entry into human cells. The exposed part of the trimer, gp140, consists of two noncovalently associated subunits, gp120 and gp41 ectodomain. A recombinant vaccine that mimics the native trimer might elicit entry-blocking antibodies and prevent virus infection. However, preparation of authentic HIV-1 trimers has been challenging. Recently, an affinity column containing the broadly neutralizing antibody 2G12 has been used to capture recombinant gp140 and prepare trimers from clade A BG505 that naturally produces stable trimers. However, this antibody-based approach may not be as effective for the diverse HIV-1 strains with different epitope signatures. Here, we report a new and simple approach to produce HIV-1 envelope trimers. The C terminus of gp140 was attached to Strep-tag II with a long linker separating the tag from the massive trimer base and glycan shield. This allowed capture of nearly homogeneous gp140 directly from the culture medium. Cleaved, uncleaved, and fully or partially glycosylated trimers from different clade viruses were produced. Extensive biochemical characterizations showed that cleavage of gp140 was not essential for trimerization, but it triggered a conformational change that channels trimers into correct glycosylation pathways, generating compact three-blade propeller-shaped trimers. Uncleaved trimers entered aberrant pathways, resulting in hyperglycosylation, nonspecific cross-linking, and conformational heterogeneity. Even the cleaved trimers showed microheterogeneity in gp41 glycosylation. These studies established a broadly applicable HIV-1 trimer production system as well as generating new insights into their assembly and maturation that collectively bear on the HIV-1 vaccine design. PMID:26088135
Attitudes toward neuroscience education in psychiatry: a national multi-stakeholder survey.
Fung, Lawrence K; Akil, Mayada; Widge, Alik; Roberts, Laura Weiss; Etkin, Amit
2015-04-01
The objective of this study is to assess the attitudes of chairs of psychiatry departments, psychiatrists, and psychiatry trainees toward neuroscience education in residency programs and beyond in order to inform future neuroscience education approaches. This multi-stakeholder survey captured data on demographics, self-assessments of neuroscience knowledge, attitudes toward neuroscience education, preferences in learning modalities, and interests in specific neuroscience topics. In 2012, the authors distributed the surveys: by paper to 133 US psychiatry department chairs and electronically through the American Psychiatric Association to 3,563 of its members (1,000 psychiatrists and 2,563 trainees). The response rates for the chair, psychiatrist, and trainee surveys were 53, 9, and 18 %, respectively. A large majority of respondents agreed with the need for more neuroscience education in general and with respect to their own training. Most respondents believed that neuroscience will help destigmatize mental illness and begin producing new treatments or personalized medicines in 5-10 years. Only a small proportion of trainees and psychiatrists, however, reported a strong knowledge base in neuroscience. Respondents also reported broad enthusiasm for transdiagnostic topics in neuroscience (such as emotion regulation and attention/cognition) and description at the level of neural circuits. This study demonstrates the opportunity and enthusiasm for teaching more neuroscience in psychiatry among a broad range of stakeholder groups. A high level of interest was also found for transdiagnostic topics and approaches. We suggest that a transdiagnostic framework may be an effective way to deliver neuroscience education to the psychiatric community and illustrate this through a case example, drawing the similarity between this neuroscience approach and problem-based formulations familiar to clinicians.
Chen, Wenqiang; Luo, Hongchen; Liu, Xingjiang; Foley, James W; Song, Xiangzhi
2016-04-05
Glutathione (GSH), cysteine (Cys), and homocysteine (Hcy) are small biomolecular thiols that are present in all cells and extracellular fluids of healthy mammals. It is well-known that each plays a separate, critically important role in human physiology and that abnormal levels of each are predictive of a variety of different disease states. Although a number of fluorescence-based methods have been developed that can detect biomolecules that contain sulfhydryl moieties, few are able to differentiate between GSH and Cys/Hcy. In this report, we demonstrate a broadly applicable approach for the design of fluorescent probes that can achieve this goal. The strategy we employ is to conjugate a fluorescence-quenching 7-nitro-2,1,3-benzoxadiazole (NBD) moiety to a selected fluorophore (Dye) through a sulfhydryl-labile ether linkage to afford nonfluorescent NBD-O-Dye. In the presence of GSH or Cys/Hcy, the ether bond is cleaved with the concomitant generation of both a nonfluorescent NBD-S-R derivative and a fluorescent dye having a characteristic intense emission band (B1). In the special case of Cys/Hcy, the NBD-S-Cys/Hcy cleavage product can undergo a further, rapid, intramolecular Smiles rearrangement to form a new, highly fluorescent NBD-N-Cys/Hcy compound (band B2); because of geometrical constraints, the GSH derived NBD-S-GSH derivative cannot undergo a Smiles rearrangement. Thus, the presence of a single B1 or double B1 + B2 signature can be used to detect and differentiate GSH from Cys/Hcy, respectively. We demonstrate the broad applicability of our approach by including in our studies members of the Flavone, Bodipy, and Coumarin dye families. Particularly, single excitation wavelength could be applied for the probe NBD-OF in the detection of GSH over Cys/Hcy in both aqueous solution and living cells.
Mass Spectrometry-Based Metabolomic and Proteomic Strategies in Organic Acidemias
Imperlini, Esther; Santorelli, Lucia; Orrù, Stefania; Scolamiero, Emanuela; Ruoppolo, Margherita
2016-01-01
Organic acidemias (OAs) are inherited metabolic disorders caused by deficiency of enzymatic activities in the catabolism of amino acids, carbohydrates, or lipids. These disorders result in the accumulation of mono-, di-, or tricarboxylic acids, generally referred to as organic acids. The OA outcomes can involve different organs and/or systems. Some OA disorders are easily managed if promptly diagnosed and treated, whereas, in others cases, such as propionate metabolism-related OAs (propionic acidemia, PA; methylmalonic acidemia, MMA), neither diet, vitamin therapy, nor liver transplantation appears to prevent multiorgan impairment. Here, we review the recent developments in dissecting molecular bases of OAs by using integration of mass spectrometry- (MS-) based metabolomic and proteomic strategies. MS-based techniques have facilitated the rapid and economical evaluation of a broad spectrum of metabolites in various body fluids, also collected in small samples, like dried blood spots. This approach has enabled the timely diagnosis of OAs, thereby facilitating early therapeutic intervention. Besides providing an overview of MS-based approaches most frequently used to study the molecular mechanisms underlying OA pathophysiology, we discuss the principal challenges of metabolomic and proteomic applications to OAs. PMID:27403441
Formalizing the Role of Agent-Based Modeling in Causal Inference and Epidemiology
Marshall, Brandon D. L.; Galea, Sandro
2015-01-01
Calls for the adoption of complex systems approaches, including agent-based modeling, in the field of epidemiology have largely centered on the potential for such methods to examine complex disease etiologies, which are characterized by feedback behavior, interference, threshold dynamics, and multiple interacting causal effects. However, considerable theoretical and practical issues impede the capacity of agent-based methods to examine and evaluate causal effects and thus illuminate new areas for intervention. We build on this work by describing how agent-based models can be used to simulate counterfactual outcomes in the presence of complexity. We show that these models are of particular utility when the hypothesized causal mechanisms exhibit a high degree of interdependence between multiple causal effects and when interference (i.e., one person's exposure affects the outcome of others) is present and of intrinsic scientific interest. Although not without challenges, agent-based modeling (and complex systems methods broadly) represent a promising novel approach to identify and evaluate complex causal effects, and they are thus well suited to complement other modern epidemiologic methods of etiologic inquiry. PMID:25480821
Accounting for estimated IQ in neuropsychological test performance with regression-based techniques.
Testa, S Marc; Winicki, Jessica M; Pearlson, Godfrey D; Gordon, Barry; Schretlen, David J
2009-11-01
Regression-based normative techniques account for variability in test performance associated with multiple predictor variables and generate expected scores based on algebraic equations. Using this approach, we show that estimated IQ, based on oral word reading, accounts for 1-9% of the variability beyond that explained by individual differences in age, sex, race, and years of education for most cognitive measures. These results confirm that adding estimated "premorbid" IQ to demographic predictors in multiple regression models can incrementally improve the accuracy with which regression-based norms (RBNs) benchmark expected neuropsychological test performance in healthy adults. It remains to be seen whether the incremental variance in test performance explained by estimated "premorbid" IQ translates to improved diagnostic accuracy in patient samples. We describe these methods, and illustrate the step-by-step application of RBNs with two cases. We also discuss the rationale, assumptions, and caveats of this approach. More broadly, we note that adjusting test scores for age and other characteristics might actually decrease the accuracy with which test performance predicts absolute criteria, such as the ability to drive or live independently.
ORIGEN-based Nuclear Fuel Inventory Module for Fuel Cycle Assessment: Final Project Report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Skutnik, Steven E.
The goal of this project, “ORIGEN-based Nuclear Fuel Depletion Module for Fuel Cycle Assessment" is to create a physics-based reactor depletion and decay module for the Cyclus nuclear fuel cycle simulator in order to assess nuclear fuel inventories over a broad space of reactor operating conditions. The overall goal of this approach is to facilitate evaluations of nuclear fuel inventories for a broad space of scenarios, including extended used nuclear fuel storage and cascading impacts on fuel cycle options such as actinide recovery in used nuclear fuel, particularly for multiple recycle scenarios. The advantages of a physics-based approach (compared tomore » a recipe-based approach which has been typically employed for fuel cycle simulators) is in its inherent flexibility; such an approach can more readily accommodate the broad space of potential isotopic vectors that may be encountered under advanced fuel cycle options. In order to develop this flexible reactor analysis capability, we are leveraging the Origen nuclear fuel depletion and decay module from SCALE to produce a standalone “depletion engine” which will serve as the kernel of a Cyclus-based reactor analysis module. The ORIGEN depletion module is a rigorously benchmarked and extensively validated tool for nuclear fuel analysis and thus its incorporation into the Cyclus framework can bring these capabilities to bear on the problem of evaluating long-term impacts of fuel cycle option choices on relevant metrics of interest, including materials inventories and availability (for multiple recycle scenarios), long-term waste management and repository impacts, etc. Developing this Origen-based analysis capability for Cyclus requires the refinement of the Origen analysis sequence to the point where it can reasonably be compiled as a standalone sequence outside of SCALE; i.e., wherein all of the computational aspects of Origen (including reactor cross-section library processing and interpolation, input and output processing, and depletion/decay solvers) can be self-contained into a single executable sequence. Further, to embed this capability into other software environments (such as the Cyclus fuel cycle simulator) requires that Origen’s capabilities be encapsulated into a portable, self-contained library which other codes can then call directly through function calls, thereby directly accessing the solver and data processing capabilities of Origen. Additional components relevant to this work include modernization of the reactor data libraries used by Origen for conducting nuclear fuel depletion calculations. This work has included the development of new fuel assembly lattices not previously available (such as for CANDU heavy-water reactor assemblies) as well as validation of updated lattices for light-water reactors updated to employ modern nuclear data evaluations. The CyBORG reactor analysis module as-developed under this workscope is fully capable of dynamic calculation of depleted fuel compositions from all commercial U.S. reactor assembly types as well as a number of international fuel types, including MOX, VVER, MAGNOX, and PHWR CANDU fuel assemblies. In addition, the Origen-based depletion engine allows for CyBORG to evaluate novel fuel assembly and reactor design types via creation of Origen reactor data libraries via SCALE. The establishment of this new modeling capability affords fuel cycle modelers a substantially improved ability to model dynamically-changing fuel cycle and reactor conditions, including recycled fuel compositions from fuel cycle scenarios involving material recycle into thermal-spectrum systems.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Feng, Hua; Li, Hong; Shen, Yue
2014-10-10
Based on an updated Hβ reverberation mapping (RM) sample of 44 nearby active galactic nuclei (AGNs), we propose a novel approach for black hole (BH) mass estimation using two filtered luminosities computed from single-epoch (SE) AGN spectra around the Hβ region. We found that the two optimal-filter luminosities extract virial information (size and virial velocity of the broad-line region, BLR) from the spectra, justifying their usage in this empirical BH mass estimator. The major advantages of this new recipe over traditional SE BH mass estimators utilizing continuum luminosity and broad-line width are (1) it has a smaller intrinsic scatter ofmore » 0.28 dex calibrated against RM masses, (2) it is extremely simple to use in practice, without any need to decompose the spectrum, and (3) it produces unambiguous and highly repeatable results even with low signal-to-noise spectra. The combination of the two luminosities can also cancel out, to some extent, systematic luminosity errors potentially introduced by uncertainties in distance or flux calibration. In addition, we recalibrated the traditional SE mass estimators using broad Hβ FWHM and monochromatic continuum luminosity at 5100 Å (L {sub 5100}). We found that using the best-fit slopes on FWHM and L {sub 5100} (derived from fitting the BLR radius-luminosity relation and the correlation between rms line dispersion and SE FWHM, respectively) rather than simple assumptions (e.g., 0.5 for L {sub 5100} and 2 for FWHM) leads to more precise SE mass estimates, improving the intrinsic scatter from 0.41 dex to 0.36 dex with respect to the RM masses. We compared different estimators and discussed their applications to the Sloan Digital Sky Survey quasar sample. Due to the limitations of the current RM sample, application of any SE recipe calibrated against RM masses to distant quasars should be treated with caution.« less
A Critical Review of Mode of Action (MOA) Assignment ...
There are various structure-based classification schemes to categorize chemicals based on mode of action (MOA) which have been applied for both eco and human health toxicology. With increasing calls to assess thousands of chemicals, some of which have little available information other than structure, clear understanding how each of these MOA schemes was devised, what information they are based on, and the limitations of each approach is critical. Several groups are developing low-tier methods to more easily classify or assess chemicals, using approaches such as the ecological threshold of concern (eco-TTC) and chemical-activity. Evaluation of these approaches and determination of their domain of applicability is partly dependent on the MOA classification that is used. The most commonly used MOA classification schemes for ecotoxicology include Verhaar and Russom (included in ASTER), both of which are used to predict acute aquatic toxicity MOA. Verhaar is a QSAR-based system that classifies chemicals into one of 4 classes, with a 5th class specified for those chemicals that are not classified in the other 4. ASTER/Russom includes 8 classifications: narcotics (3 groups), oxidative phosphorylation uncouplers, respiratory inhibitors, electrophiles/proelectrophiles, AChE inhibitors, or CNS seizure agents. Other methodologies include TEST (Toxicity Estimation Software Tool), a computational chemistry-based application that allows prediction to one of 5 broad MOA
17 CFR 41.14 - Transition period for indexes that cease being narrow-based security indexes.
Code of Federal Regulations, 2011 CFR
2011-04-01
... provision. An index that is a narrow-based security index that becomes a broad-based security index for no...-five days. An index that is a narrow-based security index that becomes a broad-based security index for...
17 CFR 41.14 - Transition period for indexes that cease being narrow-based security indexes.
Code of Federal Regulations, 2010 CFR
2010-04-01
... provision. An index that is a narrow-based security index that becomes a broad-based security index for no...-five days. An index that is a narrow-based security index that becomes a broad-based security index for...
17 CFR 41.14 - Transition period for indexes that cease being narrow-based security indexes.
Code of Federal Regulations, 2013 CFR
2013-04-01
... provision. An index that is a narrow-based security index that becomes a broad-based security index for no...-five days. An index that is a narrow-based security index that becomes a broad-based security index for...
17 CFR 41.14 - Transition period for indexes that cease being narrow-based security indexes.
Code of Federal Regulations, 2012 CFR
2012-04-01
... provision. An index that is a narrow-based security index that becomes a broad-based security index for no...-five days. An index that is a narrow-based security index that becomes a broad-based security index for...
Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-120 interface
Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark
2014-01-01
The isolation of human monoclonal antibodies (mAbs) is providing important insights regarding the specificities that underlie broad neutralization of HIV-1 (reviewed in1). Here we report a broad and extremely potent HIV-specific mAb, termed 35O22, which binds novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with an IC50<50 μg/ml. The median IC50 of neutralized viruses was 0.033 μg/ml, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed it to bind a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current mAb-based approaches to immunotherapies, prophylaxis, and vaccine design. PMID:25186731
China's Education Policy-Making: A Policy Network Perspective
ERIC Educational Resources Information Center
Han, Shuangmiao; Ye, Fugui
2017-01-01
Policy network approach has become a broadly accepted and frequently adopted practice in modern state governance, especially in the public sector. The study utilises a broadly defined policy network conceptual frame and categories of reference to trace the evolution of education policy-making in China. The study uses "The Outline of China's…
Ascertaining top evidence in emergency medicine: A modified Delphi study.
Bazak, Stephanie J; Sherbino, Jonathan; Upadhye, Suneel; Chan, Teresa
2018-06-21
CLINICIAN'S CAPSULE What is known about the topic? EM is a specialty with a broad knowledge base making it daunting for a junior resident to know where to begin the acquisition of evidence-based knowledge. What did the study ask? What list of "top papers" was formulated in the field of EM using a national Canadian Delphi approach to achieve an expert consensus? What did the study find? A list was produced of top studies relevant for Canadian EM physicians in training. Why does this study matter to clinicians? The list produced can be used as an educational resource for junior residents.
Employee assistance programs: history and program description.
Gilbert, B
1994-10-01
1. The history and development of Employee Assistance Programs (EAPs) can be traced back to the 1800s. There are currently over 10,000 EAPs in the United States. 2. Standards for program accreditation and counselor certification have been established for EAPs. The "core technology of Employee Assistance Programs" includes identification of behavioural problems based on job performance issues, expert consultation with supervisors, appropriate use of constructive confrontation, microlinkages with treatment providers and resources, macrolinkages between providers, resources, and work organizations, focus on substance abuse, and evaluation of employee success based on job performance. 3. Some EAPs take a broad brush approach, and incorporate health promotion and managed care functions.
Beyond consumer-driven health care: purchasers' expectations of all plans.
Lee, Peter V; Hoo, Emma
2006-01-01
Skyrocketing health care costs and quality deficits can only be addressed through a broad approach of quality-based benefit design. Consumer-directed health plans that are built around better consumer information tools and support hold the promise of consumer engagement, but purchasers expect these features in all types of health plans. Regardless of plan type, simply shifting costs to consumers is a threat to access and adherence to evidence-based medicine. Comparative and interactive consumer information tools, coupled with provider performance transparency and payment reform, are needed to advance accountability and support consumers in getting the right care at the right time.
No hospital left behind? Education policy lessons for value-based payment in healthcare.
Maurer, Kristin A; Ryan, Andrew M
2016-01-01
Value-based payment systems have been widely implemented in healthcare in an effort to improve the quality of care. However, these programs have not broadly improved quality, and some evidence suggests that they may increase inequities in care. No Child Left Behind is a parallel effort in education to address uneven achievement and inequalities. Yet, by penalizing the lowest performers, No Child Left Behind's approach to accountability has led to a number of unintended consequences. This article draws lessons from education policy, arguing that financial incentives should be designed to support the lowest performers to improve quality. © 2015 Society of Hospital Medicine.
Zorman, Milan; Sánchez de la Rosa, José Luis; Dinevski, Dejan
2011-12-01
It is not very often to see a symbol-based machine learning approach to be used for the purpose of image classification and recognition. In this paper we will present such an approach, which we first used on the follicular lymphoma images. Lymphoma is a broad term encompassing a variety of cancers of the lymphatic system. Lymphoma is differentiated by the type of cell that multiplies and how the cancer presents itself. It is very important to get an exact diagnosis regarding lymphoma and to determine the treatments that will be most effective for the patient's condition. Our work was focused on the identification of lymphomas by finding follicles in microscopy images provided by the Laboratory of Pathology in the University Hospital of Tenerife, Spain. We divided our work in two stages: in the first stage we did image pre-processing and feature extraction, and in the second stage we used different symbolic machine learning approaches for pixel classification. Symbolic machine learning approaches are often neglected when looking for image analysis tools. They are not only known for a very appropriate knowledge representation, but also claimed to lack computational power. The results we got are very promising and show that symbolic approaches can be successful in image analysis applications.
Pettitt, David; Arshad, Zeeshaan; Davies, Benjamin; Smith, James; French, Anna; Cole, Doug; Bure, Kim; Dopson, Sue; DiGiusto, David; Karp, Jeff; Reeve, Brock; Barker, Richard; Holländer, Georg; Brindley, David
2017-06-26
Cellular-based therapies represent a platform technology within the rapidly expanding field of regenerative medicine and are distinct from conventional therapeutics-offering a unique approach to managing what were once considered untreatable diseases. Despite a significant increase in basic science activity within the cell therapy arena, alongside a growing portfolio of cell therapy trials and promising investment, the translation of cellular-based therapeutics from "bench to bedside" remains challenging, and the number of industry products available for widespread clinical use remains comparatively low. This systematic review identifies unique intrinsic and extrinsic barriers in the cell-based therapy domain. Eight electronic databases will be searched, specifically Medline, EMBASE (OvidSP), BIOSIS & Web of Science, Cochrane Library & HEED, EconLit (ProQuest), WHOLIS WHO Library Database, PAIS International (ProQuest), and Scopus. Addition to this gray literature was searched by manually reviewing relevant work. All identified articles will be subjected for review by two authors who will decide whether or not each article passes our inclusion/exclusion criteria. Eligible papers will subsequently be reviewed, and key data extracted into a pre-designed data extraction scorecard. An assessment of the perceived impact of broad commercial barriers to the adoption of cell-based therapies will be conducted. These broad categories will include manufacturing, regulation and intellectual property, reimbursement, clinical trials, clinical adoption, ethics, and business models. This will inform further discussion in the review. There is no PROSPERO registration number. Through a systematic search and appraisal of available literature, this review will identify key challenges in the commercialization pathway of cellular-based therapeutics and highlights significant barriers impeding successful clinical adoption. This will aid in creating an adaptable, acceptable, and harmonized approach supported by apposite regulatory frameworks and pertinent expertise throughout the respective stages of the adoption cycle to facilitate the adoption of new products and technologies in the industry.
A Review of Current and Emerging Approaches to Pain Management in the Emergency Department.
Todd, Knox H
2017-12-01
Pain is the most common symptom prompting an emergency department visit and emergency physicians are responsible for managing both acute pain and acute exacerbations of chronic pain resulting from a broad range of illnesses and injuries. The responsibility to treat must be balanced by the duty to limit harm resulting from analgesics. In recent years, opioid-related adverse effects, including overdose and deaths, have increased dramatically in the USA. In response to the US opioid crisis, emergency physicians have broadened their analgesic armamentarium to include a variety of non-opioid approaches. For some of these therapies, sparse evidence exists to support their efficacy for emergency department use. The purpose of this paper is to review historical trends and emerging approaches to emergency department analgesia, with a particular focus on the USA and Canada. We conducted a qualitative review of past and current descriptive studies of emergency department pain practice, as well as clinical trials of emerging pain treatment modalities. The review considers the increasing use of non-opioid and multimodal analgesic therapies, including migraine therapies, regional anesthesia, subdissociative-dose ketamine, nitrous oxide, intravenous lidocaine and gabapentinoids, as well as broad programmatic initiatives promoting the use of non-opioid analgesics and nonpharmacologic interventions. While migraine therapies, regional anesthesia, nitrous oxide and subdissociative-dose ketamine are supported by a relatively robust evidence base, data supporting the emergency department use of intravenous lidocaine, gabapentinoids and various non-pharmacologic analgesic interventions remain sparse. Additional research on the relative safety and efficacy of non-opioid approaches to emergency department analgesia is needed. Despite a limited research base, it is likely that non-opioid analgesic modalities will be employed with increasing frequency. A new generation of emergency physicians is seeking additional training in pain medicine and increasing dialogue between emergency medicine and pain medicine researchers, educators and clinicians could contribute to better management of emergency department pain.
Forecasting conditional climate-change using a hybrid approach
Esfahani, Akbar Akbari; Friedel, Michael J.
2014-01-01
A novel approach is proposed to forecast the likelihood of climate-change across spatial landscape gradients. This hybrid approach involves reconstructing past precipitation and temperature using the self-organizing map technique; determining quantile trends in the climate-change variables by quantile regression modeling; and computing conditional forecasts of climate-change variables based on self-similarity in quantile trends using the fractionally differenced auto-regressive integrated moving average technique. The proposed modeling approach is applied to states (Arizona, California, Colorado, Nevada, New Mexico, and Utah) in the southwestern U.S., where conditional forecasts of climate-change variables are evaluated against recent (2012) observations, evaluated at a future time period (2030), and evaluated as future trends (2009–2059). These results have broad economic, political, and social implications because they quantify uncertainty in climate-change forecasts affecting various sectors of society. Another benefit of the proposed hybrid approach is that it can be extended to any spatiotemporal scale providing self-similarity exists.
Gironés, Xavier; Carbó-Dorca, Ramon; Ponec, Robert
2003-01-01
A new approach allowing the theoretical modeling of the electronic substituent effect is proposed. The approach is based on the use of fragment Quantum Self-Similarity Measures (MQS-SM) calculated from domain averaged Fermi Holes as new theoretical descriptors allowing for the replacement of Hammett sigma constants in QSAR models. To demonstrate the applicability of this new approach its formalism was applied to the description of the substituent effect on the dissociation of a broad series of meta and para substituted benzoic acids. The accuracy and the predicting power of this new approach was tested on the comparison with a recent exhaustive study by Sullivan et al. It has been shown that the accuracy and the predicting power of both procedures is comparable, but, in contrast to a five-parameter correlation equation necessary to describe the data in the study, our approach is more simple and, in fact, only a simple one-parameter correlation equation is required.
Poulos, Roslyn G; Donaldson, Alex; McLeod, Brent
2012-01-01
Sports injuries are an important public health issue. A multi-agency key stakeholder partnership was formed to develop a state-wide response to sports injury prevention in New South Wales, Australia. This study evaluated the partnership approach to injury prevention policy development. The partnership approach to policy development was evaluated pre- and post-partnership using semi-structured telephone interviews and questionnaire data gathered from participants. Participants were satisfied with the partnership operation and outcomes. Challenges included: maintaining focus and efficiency; time constraints; sector diversity limiting the likelihood of addressing needs and reaching consensus; and ensuring commitment from all relevant organisations. Potential benefits included: a sense of policy ownership; a broad-based approach across the sector and savings from resource sharing. Policy resulted from a shared understanding of the injury problem, and of an appropriate response. A credible industry leader, investment in partnership management and a consultative approach facilitated the success of the partnership.
Structural Design Methodology Based on Concepts of Uncertainty
NASA Technical Reports Server (NTRS)
Lin, K. Y.; Du, Jiaji; Rusk, David
2000-01-01
In this report, an approach to damage-tolerant aircraft structural design is proposed based on the concept of an equivalent "Level of Safety" that incorporates past service experience in the design of new structures. The discrete "Level of Safety" for a single inspection event is defined as the compliment of the probability that a single flaw size larger than the critical flaw size for residual strength of the structure exists, and that the flaw will not be detected. The cumulative "Level of Safety" for the entire structure is the product of the discrete "Level of Safety" values for each flaw of each damage type present at each location in the structure. Based on the definition of "Level of Safety", a design procedure was identified and demonstrated on a composite sandwich panel for various damage types, with results showing the sensitivity of the structural sizing parameters to the relative safety of the design. The "Level of Safety" approach has broad potential application to damage-tolerant aircraft structural design with uncertainty.
Dose selection based on physiologically based pharmacokinetic (PBPK) approaches.
Jones, Hannah M; Mayawala, Kapil; Poulin, Patrick
2013-04-01
Physiologically based pharmacokinetic (PBPK) models are built using differential equations to describe the physiology/anatomy of different biological systems. Readily available in vitro and in vivo preclinical data can be incorporated into these models to not only estimate pharmacokinetic (PK) parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. They provide a mechanistic framework to understand and extrapolate PK and dose across in vitro and in vivo systems and across different species, populations and disease states. Using small molecule and large molecule examples from the literature and our own company, we have shown how PBPK techniques can be utilised for human PK and dose prediction. Such approaches have the potential to increase efficiency, reduce the need for animal studies, replace clinical trials and increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however some limitations need to be addressed to realise its application and utility more broadly.
High-Throughput Lectin Microarray-Based Analysis of Live Cell Surface Glycosylation
Li, Yu; Tao, Sheng-ce; Zhu, Heng; Schneck, Jonathan P.
2011-01-01
Lectins, plant-derived glycan-binding proteins, have long been used to detect glycans on cell surfaces. However, the techniques used to characterize serum or cells have largely been limited to mass spectrometry, blots, flow cytometry, and immunohistochemistry. While these lectin-based approaches are well established and they can discriminate a limited number of sugar isomers by concurrently using a limited number of lectins, they are not amenable for adaptation to a high-throughput platform. Fortunately, given the commercial availability of lectins with a variety of glycan specificities, lectins can be printed on a glass substrate in a microarray format to profile accessible cell-surface glycans. This method is an inviting alternative for analysis of a broad range of glycans in a high-throughput fashion and has been demonstrated to be a feasible method of identifying binding-accessible cell surface glycosylation on living cells. The current unit presents a lectin-based microarray approach for analyzing cell surface glycosylation in a high-throughput fashion. PMID:21400689
The "shoulds" and "should nots" of moral emotions: a self-regulatory perspective on shame and guilt.
Sheikh, Sana; Janoff-Bulman, Ronnie
2010-02-01
A self-regulatory framework for distinguishing between shame and guilt was tested in three studies. Recently, two forms of moral regulation based on approach versus avoidance motivation have been proposed in the literature. Proscriptive regulation is sensitive to negative outcomes, inhibition based, and focused on what we should not do. Prescriptive regulation is sensitive to positive outcomes, activation based, and focused on what we should do. In the current research, consistent support was found for shame's proscriptive and guilt's prescriptive moral underpinnings. Study 1 found a positive association between avoidance orientation and shame proneness and between approach orientation and guilt proneness. In Study 2, priming a proscriptive orientation increased shame and priming a prescriptive orientation increased guilt. In Study 3, transgressions most apt to represent proscriptive and prescriptive violations predicted subsequent judgments of shame and guilt, respectively. This self-regulatory perspective provides a broad interpretive framework for understanding and extending past research findings.
TIGER: the universal biosensor
NASA Astrophysics Data System (ADS)
Hofstadler, Steven A.; Sampath, Rangarajan; Blyn, Lawrence B.; Eshoo, Mark W.; Hall, Thomas A.; Jiang, Yun; Drader, Jared J.; Hannis, James C.; Sannes-Lowery, Kristin A.; Cummins, Lendell L.; Libby, Brian; Walcott, Demetrius J.; Schink, Amy; Massire, Christian; Ranken, Raymond; Gutierrez, Jose; Manalili, Sheri; Ivy, Cristina; Melton, Rachael; Levene, Harold; Barrett-Wilt, Greg; Li, Feng; Zapp, Vanessa; White, Neill; Samant, Vivek; McNeil, John A.; Knize, Duane; Robbins, David; Rudnick, Karl; Desai, Anjali; Moradi, Emily; Ecker, David J.
2005-03-01
In this work, we describe a strategy for the detection and characterization of microorganisms associated with a potential biological warfare attack or a natural outbreak of an emerging infectious disease. This approach, termed TIGER (Triangulation Identification for the Genetic Evaluation of Risks), relies on mass spectrometry-derived base composition signatures obtained from PCR amplification of broadly conserved regions of the microbial genome(s) in a sample. The sample can be derived from air filtration devices, clinical samples, or other sources. Core to this approach are "intelligent PCR primers" that target broadly conserved regions of microbial genomes that flank variable regions. This approach requires that high-performance mass measurements be made on PCR products in the 80-140 bp size range in a high-throughput, robust modality. As will be demonstrated, the concept is equally applicable to bacteria and viruses and could be further applied to fungi and protozoa. In addition to describing the fundamental strategy of this approach, several specific examples of TIGER are presented that illustrate the impact this approach could have on the way biological weapons attacks are detected and the way that the etiologies of infectious diseases are determined. The first example illustrates how any bacterial species might be identified, using Bacillus anthracis as the test agent. The second example demonstrates how DNA-genome viruses are identified using five members of Poxviridae family, whose members includes Variola virus, the agent responsible for smallpox. The third example demonstrates how RNA-genome viruses are identified using the Alphaviruses (VEE, WEE, and EEE) as representative examples. These examples illustrate how the TIGER technology can be applied to create a universal identification strategy for all pathogens, including those that infect humans, livestock, and plants.
NASA Astrophysics Data System (ADS)
Šilhán, Karel; Stoffel, Markus
2015-05-01
Different approaches and thresholds have been utilized in the past to date landslides with growth ring series of disturbed trees. Past work was mostly based on conifer species because of their well-defined ring boundaries and the easy identification of compression wood after stem tilting. More recently, work has been expanded to include broad-leaved trees, which are thought to produce less and less evident reactions after landsliding. This contribution reviews recent progress made in dendrogeomorphic landslide analysis and introduces a new approach in which landslides are dated via ring eccentricity formed after tilting. We compare results of this new and the more conventional approaches. In addition, the paper also addresses tree sensitivity to landslide disturbance as a function of tree age and trunk diameter using 119 common beech (Fagus sylvatica L.) and 39 Crimean pine (Pinus nigra ssp. pallasiana) trees growing on two landslide bodies. The landslide events reconstructed with the classical approach (reaction wood) also appear as events in the eccentricity analysis, but the inclusion of eccentricity clearly allowed for more (162%) landslides to be detected in the tree-ring series. With respect to tree sensitivity, conifers and broad-leaved trees show the strongest reactions to landslides at ages comprised between 40 and 60 years, with a second phase of increased sensitivity in P. nigra at ages of ca. 120-130 years. These phases of highest sensitivities correspond with trunk diameters at breast height of 6-8 and 18-22 cm, respectively (P. nigra). This study thus calls for the inclusion of eccentricity analyses in future landslide reconstructions as well as for the selection of trees belonging to different age and diameter classes to allow for a well-balanced and more complete reconstruction of past events.
Learner-Adaptive Educational Technology for Simulation in Healthcare: Foundations and Opportunities.
Lineberry, Matthew; Dev, Parvati; Lane, H Chad; Talbot, Thomas B
2018-06-01
Despite evidence that learners vary greatly in their learning needs, practical constraints tend to favor ''one-size-fits-all'' educational approaches, in simulation-based education as elsewhere. Adaptive educational technologies - devices and/or software applications that capture and analyze relevant data about learners to select and present individually tailored learning stimuli - are a promising aid in learners' and educators' efforts to provide learning experiences that meet individual needs. In this article, we summarize and build upon the 2017 Society for Simulation in Healthcare Research Summit panel discussion on adaptive learning. First, we consider the role of adaptivity in learning broadly. We then outline the basic functions that adaptive learning technologies must implement and the unique affordances and challenges of technology-based approaches for those functions, sharing an illustrative example from healthcare simulation. Finally, we consider future directions for accelerating research, development, and deployment of effective adaptive educational technology and techniques in healthcare simulation.
Performance characterization of material identification systems
NASA Astrophysics Data System (ADS)
Brown, Christopher D.; Green, Robert L.
2006-10-01
In recent years a number of analytical devices have been proposed and marketed specifically to enable field-based material identification. Technologies reliant on mass, near- and mid-infrared, and Raman spectroscopies are available today, and other platforms are imminent. These systems tend to perform material recognition based on an on-board library of material signatures. While figures of merit for traditional quantitative analytical sensors are broadly established (e.g., SNR, selectivity, sensitivity, limit of detection/decision), measures of performance for material identification systems have not been systematically discussed. In this paper we present an approach to performance characterization similar in spirit to ROC curves, but including elements of precision-recall curves and specialized for the intended-use of material identification systems. Important experimental considerations are discussed, including study design, sources of bias, uncertainty estimation, and cross-validation and the approach as a whole is illustrated using a commercially available handheld Raman material identification system.
NASA Astrophysics Data System (ADS)
Lenderink, Geert; Attema, Jisk
2015-08-01
Scenarios of future changes in small scale precipitation extremes for the Netherlands are presented. These scenarios are based on a new approach whereby changes in precipitation extremes are set proportional to the change in water vapor amount near the surface as measured by the 2m dew point temperature. This simple scaling framework allows the integration of information derived from: (i) observations, (ii) a new unprecedentedly large 16 member ensemble of simulations with the regional climate model RACMO2 driven by EC-Earth, and (iii) short term integrations with a non-hydrostatic model Harmonie. Scaling constants are based on subjective weighting (expert judgement) of the three different information sources taking also into account previously published work. In all scenarios local precipitation extremes increase with warming, yet with broad uncertainty ranges expressing incomplete knowledge of how convective clouds and the atmospheric mesoscale circulation will react to climate change.
Documentation and tagging of casualties in multiple casualty incidents.
Garner, Alan
2003-01-01
The use of triage tags is widely advocated as a tool to improve the management of multiple casualty incident scenes. However, there are no published reports to suggest that triage tags have improved the management of incidents involving more than 24 persons, and a number of reports have detailed problems associated with triage tag use. Alternative systems of scene management such as geographical triage have been successfully used in very large incidents, and are recommended as an alternative to triage tags. Documentation cards attached to casualties may be of use in situations where casualties will pass through an extended evacuation chain, and clear labels for deceased casualties are of benefit as they discourage repeat assessments. Adoption of an evidence-based approach to multiple casualty incident scene management will require a paradigm shift in the thinking of ambulance services. A broad-based educational approach that encourages critical reappraisal of existing procedures is recommended.
Dynamical effects in Bragg coherent x-ray diffraction imaging of finite crystals
NASA Astrophysics Data System (ADS)
Shabalin, A. G.; Yefanov, O. M.; Nosik, V. L.; Bushuev, V. A.; Vartanyants, I. A.
2017-08-01
We present simulations of Bragg coherent x-ray diffractive imaging (CXDI) data from finite crystals in the frame of the dynamical theory of x-ray diffraction. The developed approach is based on a numerical solution of modified Takagi-Taupin equations and can be applied for modeling of a broad range of x-ray diffraction experiments with finite three-dimensional crystals of arbitrary shape also in the presence of strain. We performed simulations for nanocrystals of a cubic and hemispherical shape of different sizes and provided a detailed analysis of artifacts in the Bragg CXDI reconstructions introduced by the dynamical diffraction. Based on our theoretical analysis we developed an analytical procedure to treat effects of refraction and absorption in the reconstruction. Our results elucidate limitations for the kinematical approach in the Bragg CXDI and suggest a natural criterion to distinguish between kinematical and dynamical cases in coherent x-ray diffraction on a finite crystal.
Teacher in a problem-based learning environment - Jack of all trades?
NASA Astrophysics Data System (ADS)
Dahms, Mona Lisa; Spliid, Claus Monrad; Nielsen, Jens Frederik Dalsgaard
2017-11-01
Problem-based learning (PBL) is one among several approaches to active learning. Being a teacher in a PBL environment can, however, be a challenge because of the need to support students' learning within a broad 'landscape of learning'. In this article we will analyse the landscape of learning by use of the study activity model (SAM) developed by the Danish University Colleges, with the aim of investigating to which extent this may lead to explication and clarification concerning the challenges faced by teachers in a PBL environment. In the case study, the SAM is applied to the first semester of an engineering programme at Aalborg University, a university setting where the PBL approach to teaching and learning is dominant. The results of the analysis are presented and discussed, and the conclusion is that the model, in spite of some shortcomings, is useful in clarifying the role of the teacher in a PBL environment.
Carter, Sarah K.; Carr, Natasha B.; Miller, Kevin H.; Wood, David J.A.
2017-01-19
The Bureau of Land Management (BLM) is implementing a landscape approach to resource management (hereafter, landscape approach) to more effectively work with partners and understand the effects of management decisions. A landscape approach is a set of concepts and principles used to guide resource management when multiple stakeholders are involved and goals include diverse and sustainable social, environmental, and economic outcomes. Core principles of a landscape approach include seeking meaningful participation of diverse stakeholders, considering diverse resource values in multifunctional landscapes, acknowledging the tradeoffs needed to meet diverse objectives in the context of sustainable resource management, and addressing the complexity of social and ecological processes by embracing interdisciplinarity and considering multiple and broad spatial and temporal perspectives.In chapter 1, we outline the overall goal of this report: to provide a conceptual foundation and framework for implementing a landscape approach to resource management in the BLM, focusing on the role of multiscale natural resource monitoring and assessment information. In chapter 2, we describe a landscape approach to resource management. BLM actions taken to implement a landscape approach include a major effort to compile broad-scale data on natural resource status and condition across much of the west. These broadscale data now provide a regional context for interpreting monitoring data collected at individual sites and informing decisions made for local projects. We also illustrate the utility of using multiscale data to understand potential effects of different resource management decisions, define relevant terms in landscape ecology, and identify spatial scales at which planning and management decisions may be evaluated.In chapter 3, we describe how the BLM Rapid Ecoregional Assessment program and Assessment, Inventory and Monitoring program may be integrated to provide the multiscale monitoring data needed to inform a landscape approach. We propose six core, broad-scale indicators of natural resource status and condition: the amount, spatial distribution, patch size and connectivity of ecosystems and wildlife habitats, and the pattern of existing development across the landscape. Additional supplemental broad-scale indicators may include fire return intervals, distributions of invasive species, and vulnerability of ecosystems to a changing climate. Landscape intactness is an additional derived indicator that is calculated from one or more of the core and supplemental broad-scale indicators. We then outline a process for assessing broad-scale indicators that is consistent with the overall BLM Assessment, Inventory, and Monitoring process, facilitating development of a multiscale natural resource monitoring program. Finally, we describe how broad-scale indicators of natural resource status and condition may guide field monitoring implemented through the BLM Assessment, Inventory and Monitoring program and help address complex management questions.In chapter 4, we consider the specific question of assessing the ecological integrity of rangelands across the western United States. We first define ecological integrity and its relation to land health. We then suggest that a combination of six local-scale indicators collected through field sampling at individual sites and five complementary broad-scale indicators together provide information on the composition, structure, and function of rangelands. The terrestrial monitoring indicators collected at the level of individual field sites are the amount of bare ground, vegetation composition (including invasive plants and plants of management concern), vegetation height, and the proportion of the soil surface in large intercanopy gaps. The broad-scale indicators are vegetation amount, distribution, patch size, connectivity, and productivity, along with the pattern of terrestrial development. Our suggested approach to quantifying ecological integrity focuses specifically on informing management of public lands for multiple resource uses, and illustrates how existing data collected through BLM monitoring and assessment programs may be used together to provide multiscale information on land condition across broad extents.In chapter 5, we develop a method for quantifying landscape intactness and apply this method to the western United States. Our multiscale index of landscape intactness is designed to be defensible, decomposable, and easy to understand. The foundation of the multiscale index of landscape intactness is the surface disturbance footprint of anthropogenic development, including energy and urban development, roads and railroads, cultivated croplands, surface mines and quarries, and energy transmission lines and pipelines. The index represents a gradient of anthropogenic influence as represented by development summarized at two spatial scales of analysis: 2.5 and 20 kilometers. We provide several example applications of the index, illustrating how these data may inform natural resource decisions at the spatial extent of BLM field and district offices, states, ecoregions, and the western United States. We find that 19.2 percent of lands managed by the BLM across the 17 western states of the conterminous United States had the highest landscape intactness. The largest intact areas occur on public lands at high elevations or in the Great Basin.We believe the frameworks, processes, and analyses provided in this report will improve the ability of the BLM to identify and evaluate potential direct and indirect effects of management actions (such as habitat restoration and renewable energy development), and assist the BLM in further implementing a landscape approach to resource management.
Elmendorf, Sarah C; Henry, Gregory H R; Hollister, Robert D; Fosaa, Anna Maria; Gould, William A; Hermanutz, Luise; Hofgaard, Annika; Jónsdóttir, Ingibjörg S; Jónsdóttir, Ingibjörg I; Jorgenson, Janet C; Lévesque, Esther; Magnusson, Borgþór; Molau, Ulf; Myers-Smith, Isla H; Oberbauer, Steven F; Rixen, Christian; Tweedie, Craig E; Walker, Marilyn D; Walker, Marilyn
2015-01-13
Inference about future climate change impacts typically relies on one of three approaches: manipulative experiments, historical comparisons (broadly defined to include monitoring the response to ambient climate fluctuations using repeat sampling of plots, dendroecology, and paleoecology techniques), and space-for-time substitutions derived from sampling along environmental gradients. Potential limitations of all three approaches are recognized. Here we address the congruence among these three main approaches by comparing the degree to which tundra plant community composition changes (i) in response to in situ experimental warming, (ii) with interannual variability in summer temperature within sites, and (iii) over spatial gradients in summer temperature. We analyzed changes in plant community composition from repeat sampling (85 plant communities in 28 regions) and experimental warming studies (28 experiments in 14 regions) throughout arctic and alpine North America and Europe. Increases in the relative abundance of species with a warmer thermal niche were observed in response to warmer summer temperatures using all three methods; however, effect sizes were greater over broad-scale spatial gradients relative to either temporal variability in summer temperature within a site or summer temperature increases induced by experimental warming. The effect sizes for change over time within a site and with experimental warming were nearly identical. These results support the view that inferences based on space-for-time substitution overestimate the magnitude of responses to contemporary climate warming, because spatial gradients reflect long-term processes. In contrast, in situ experimental warming and monitoring approaches yield consistent estimates of the magnitude of response of plant communities to climate warming.
A Comprehensive Approach to Evaluating Hazards of Microplastics in the Marine Environment
NASA Astrophysics Data System (ADS)
Noble, A. E.; Lewis, A. S.; Butler, C. H.; Lunsman, T. D.; Verslycke, T.
2016-02-01
Plastic debris in the environment is a growing global concern, and the past decade has brought particular attention to a small size range of plastic debris, often referred to as microplastics. The potential environmental effects of microplastics are complex and, as yet, poorly understood. Emerging research suggests that specific plastic types pose environmental risks primarily via indirect toxicity caused by hazardous compounds associated with microplastics (e.g., monomers, additives, and sorbed environmental pollutants). However, our understanding of the physicochemical properties that determine the environmental fate and toxicity of microplastics is limited. Some recent regulatory initiatives have been broad, seeking to regulate all solid synthetic polymers ≤5 mm despite the lack of a sound technical basis for using solely a size-based cutoff. Such broad regulation of all solid synthetic polymers may actually discourage the use and innovation of less hazardous synthetic polymers and "greener" substitutes. We propose a polymer-specific approach to evaluating potential hazards of microplastics, informed by the state of the science and current research needs. This approach relies on identifying focused tests and analyses to set criteria for determining the degree to which a solid synthetic polymer is likely to pose environmental risk. Important considerations include degradation, sorptive capacity, and monomer/additive content. Our approach is a first step toward a more comprehensive way to evaluate the environmental hazards and risks of microplastics. Our goals are to develop clearer criteria to assess future solid synthetic polymers of unknown concern, inform microplastics regulation, and drive innovation of greener solutions to this global concern.
What Synthesis Methodology Should I Use? A Review and Analysis of Approaches to Research Synthesis.
Schick-Makaroff, Kara; MacDonald, Marjorie; Plummer, Marilyn; Burgess, Judy; Neander, Wendy
2016-01-01
When we began this process, we were doctoral students and a faculty member in a research methods course. As students, we were facing a review of the literature for our dissertations. We encountered several different ways of conducting a review but were unable to locate any resources that synthesized all of the various synthesis methodologies. Our purpose is to present a comprehensive overview and assessment of the main approaches to research synthesis. We use 'research synthesis' as a broad overarching term to describe various approaches to combining, integrating, and synthesizing research findings. We conducted an integrative review of the literature to explore the historical, contextual, and evolving nature of research synthesis. We searched five databases, reviewed websites of key organizations, hand-searched several journals, and examined relevant texts from the reference lists of the documents we had already obtained. We identified four broad categories of research synthesis methodology including conventional, quantitative, qualitative, and emerging syntheses. Each of the broad categories was compared to the others on the following: key characteristics, purpose, method, product, context, underlying assumptions, unit of analysis, strengths and limitations, and when to use each approach. The current state of research synthesis reflects significant advancements in emerging synthesis studies that integrate diverse data types and sources. New approaches to research synthesis provide a much broader range of review alternatives available to health and social science students and researchers.
Del Fiol, Guilherme; Michelson, Matthew; Iorio, Alfonso; Cotoi, Chris; Haynes, R Brian
2018-06-25
A major barrier to the practice of evidence-based medicine is efficiently finding scientifically sound studies on a given clinical topic. To investigate a deep learning approach to retrieve scientifically sound treatment studies from the biomedical literature. We trained a Convolutional Neural Network using a noisy dataset of 403,216 PubMed citations with title and abstract as features. The deep learning model was compared with state-of-the-art search filters, such as PubMed's Clinical Query Broad treatment filter, McMaster's textword search strategy (no Medical Subject Heading, MeSH, terms), and Clinical Query Balanced treatment filter. A previously annotated dataset (Clinical Hedges) was used as the gold standard. The deep learning model obtained significantly lower recall than the Clinical Queries Broad treatment filter (96.9% vs 98.4%; P<.001); and equivalent recall to McMaster's textword search (96.9% vs 97.1%; P=.57) and Clinical Queries Balanced filter (96.9% vs 97.0%; P=.63). Deep learning obtained significantly higher precision than the Clinical Queries Broad filter (34.6% vs 22.4%; P<.001) and McMaster's textword search (34.6% vs 11.8%; P<.001), but was significantly lower than the Clinical Queries Balanced filter (34.6% vs 40.9%; P<.001). Deep learning performed well compared to state-of-the-art search filters, especially when citations were not indexed. Unlike previous machine learning approaches, the proposed deep learning model does not require feature engineering, or time-sensitive or proprietary features, such as MeSH terms and bibliometrics. Deep learning is a promising approach to identifying reports of scientifically rigorous clinical research. Further work is needed to optimize the deep learning model and to assess generalizability to other areas, such as diagnosis, etiology, and prognosis. ©Guilherme Del Fiol, Matthew Michelson, Alfonso Iorio, Chris Cotoi, R Brian Haynes. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 25.06.2018.
Kibel, Mia; Vanstone, Meredith
2017-12-01
When evaluating new morally complex health technologies, policy decision-makers consider a broad range of different evaluations, which may include the technology's clinical effectiveness, cost effectiveness, and social or ethical implications. This type of holistic assessment is challenging, because each of these evaluations may be grounded in different and potentially contradictory assumptions about the technology's value. One such technology where evaluations conflict is Non-Invasive Prenatal Testing (NIPT). Cost-effectiveness evaluations of NIPT often assess NIPT's ability to deliver on goals (i.e preventing the birth of children with disabilities) that social and ethical analyses suggest it should not have. Thus, cost effectiveness analyses frequently contradict social and ethical assessments of NIPT's value. We use the case of NIPT to explore how economic evaluations using a capabilities approach may be able to capture a broader, more ethical view of the value of NIPT. The capabilities approach is an evaluative framework which bases wellbeing assessments on a person's abilities, rather than their expressed preferences. It is linked to extra-welfarist approaches in health economic assessment. Beginning with Nussbaum's capability framework, we conducted a directed qualitative content analysis of interview data collected in 2014 from 27 Canadian women with personal experience of NIPT. We found that eight of Nussbaum's ten capabilities related to options, states, or choices that women valued in the context of NIPT, and identified one new capability. Our findings suggest that women value NIPT for its ability to provide more and different choices in the prenatal care pathway, and that a capabilities approach can indeed capture the value of NIPT in a way that goes beyond measuring health outcomes of ambiguous social and ethical value. More broadly, the capabilities approach may serve to resolve contradictions between ethical and economic evaluations of health technologies, and contribute to extra-welfarist approaches in the assessment of morally complex health technologies. Copyright © 2017 Elsevier Ltd. All rights reserved.
Loeser, Helen; O'Sullivan, Patricia; Irby, David M
2007-04-01
After successive Liaison Committee on Medical Education accreditation reports that criticized the University of California, San Francisco, School of Medicine for lack of instructional innovation and curriculum oversight, the dean issued a mandate for curriculum reform in 1997. Could a medical school that prided itself on innovation in research and health care do the same in education? The authors describe their five-phase curriculum change process and correlate this to an eight-step leadership model. The first phase of curricular change is to establish a compelling need for change; it requires leaders to create a sense of urgency and build a guiding coalition to achieve action. The second phase of curriculum reform is to envision a bold new curriculum; leaders must develop such a vision and communicate it broadly. The third phase is to design curriculum and obtain the necessary approvals; this requires leaders to empower broad-based action and generate short-term wins. In the fourth phase, specific courses are developed for the new curriculum, and leaders continue to empower broad-based action, generate short-term wins, consolidate gains, and produce more change. During the fifth phase of implementation and evaluation, leaders need to further consolidate gains, produce more change, and anchor new approaches in the institution. Arising from this experience and the correlation of curricular change phases with leadership steps, the authors identify 27 specific leadership strategies they employed in their curricular reform process.
Marketing the `Broad Line': Invitations to STEM education in a Swedish recruitment campaign
NASA Astrophysics Data System (ADS)
Andrée, Maria; Hansson, Lena
2013-01-01
In many Western societies, there is a concern about the tendency of young people not choosing Science, Technology, Engineering, and Mathematics (STEM) education and occupations. In response, different initiatives have been launched. If one believes that science should have a place in more young people's lives, an important question is to what extent recruitment campaigns communicate messages that open up for STEM education to become relevant in young people's identity formation. Here, we analyse a Swedish government-initiated, primarily Internet-based recruitment attempt ('The Broad Line Campaign') aimed at increasing the number of young people choosing the natural science programme in upper secondary school. The campaign is based on marketing principles and deliberately draws on identity issues. The data analysed consists of campaign films and written resources describing the campaign. Data are analysed by use of the constant comparative approach in order to produce categories describing different messages about why to engage in STEM education. These messages are then analysed from an identity perspective using the concept of subjective values. Our results show that the messages communicated in the Broad Line campaign emphasise utility value, attainment value and relative cost rather than interest-enjoyment. The campaign communicates that the natural science programme is to be associated with a high attainment value without establishing relations to the field of science. Finally, potential consequences of the communicated messages in the campaign are discussed in light of previous research.
Klimochkin, Yuri N; Shiryaev, Vadim A; Petrov, Pavel V; Radchenko, Eugene V; Palyulin, Vladimir A; Zefirov, Nikolay S
2016-01-01
The influenza A virus M2 proton channel plays a critical role in its life cycle. However, known M2 inhibitors have lost their clinical efficacy due to the spread of resistant mutant channels. Thus, the search for broad-spectrum M2 channel inhibitors is of great importance. The goal of the present work was to develop a general approach supporting the design of ligands interacting with multiple labile targets and to propose on its basis the potential broad-spectrum inhibitors of the M2 proton channel. The dynamic dimer-of-dimers structures of the three primary M2 target variants, wild-type, S31N and V27A, were modeled by molecular dynamics and thoroughly analyzed in order to define the inhibitor binding sites. The potential inhibitor structures were identified by molecular docking and their binding was verified by molecular dynamics simulation. The binding sites of the M2 proton channel inhibitors were analyzed, a number of potential broad-spectrum inhibitors were identified and the binding modes and probable mechanisms of action of one promising compound were clarified. Using the molecular dynamics and molecular docking techniques, we have refined the dynamic dimer-ofdimers structures of the WT, S31N and V27A variants of the M2 proton channel of the influenza A virus, analyzed the inhibitor binding sites, identified a number of potential broad-spectrum inhibitor structures targeting them, and clarified the binding modes and probable mechanisms of action of one promising compound. The proposed approach is also suitable for the design of ligands interacting with other multiple labile targets.
Vu, Maihan B.; Halladay, Jacqueline R.; Miller, Cassandra; Garcia, Beverly A.; Cummings, Doyle M.; Cene, Crystal W.; Hinderliter, Alan; Little, Edwin; Rachide, Marjorie; DeWalt, Darren
2014-01-01
Introduction Patient and practice perspectives can inform development of team-based approaches to improving blood pressure control in primary care. We used a community-based participatory research approach to assess patient and practice perceptions regarding the value of team-based strategies for controlling blood pressure in a rural North Carolina population from 2010 through 2012. Methods In-depth interviews were conducted with 41 adults with hypertension, purposely sampled to include diversity of sex, race, literacy, and blood pressure control, and with key office staff at 5 rural primary care practices in the southeastern US “stroke belt.” Interviews explored barriers to controlling blood pressure, the practice’s role in controlling blood pressure, and opinions on the use of team care delivery. Results Patients reported that provider strategies to optimize blood pressure control should include regular visits, medication adjustment, side-effect discussion, and behavioral counseling. When discussing team-based approaches to hypertension care, patients valued verbal encouragement, calls from the doctor’s office, and the opportunity to ask questions. However, they voiced concerns about the effect of having too many people involved in their care. Practice staff focused on multiple, broad methods to control blood pressure including counseling, regular office visits, media to improve awareness, and support groups. An explicit focus of delivering care as teams was a newer concept. Conclusion When developing a team approach to hypertension treatment, patients value high-quality communication and not losing their primary relationship with their provider. Practice staff members were open to a team-based approach but had limited knowledge of what such an approach would entail. PMID:24762533
Low-cost fabrication technologies for nanostructures: state-of-the-art and potential
NASA Astrophysics Data System (ADS)
Santos, A.; Deen, M. J.; Marsal, L. F.
2015-01-01
In the last decade, some low-cost nanofabrication technologies used in several disciplines of nanotechnology have demonstrated promising results in terms of versatility and scalability for producing innovative nanostructures. While conventional nanofabrication technologies such as photolithography are and will be an important part of nanofabrication, some low-cost nanofabrication technologies have demonstrated outstanding capabilities for large-scale production, providing high throughputs with acceptable resolution and broad versatility. Some of these nanotechnological approaches are reviewed in this article, providing information about the fundamentals, limitations and potential future developments towards nanofabrication processes capable of producing a broad range of nanostructures. Furthermore, in many cases, these low-cost nanofabrication approaches can be combined with traditional nanofabrication technologies. This combination is considered a promising way of generating innovative nanostructures suitable for a broad range of applications such as in opto-electronics, nano-electronics, photonics, sensing, biotechnology or medicine.
A model-based approach for the scattering-bar printing avoidance
NASA Astrophysics Data System (ADS)
Du, Yaojun; Li, Liang; Zhang, Jingjing; Shao, Feng; Zuniga, Christian; Deng, Yunfei
2018-03-01
As the technology node for the semiconductor manufacturing approaches advanced nodes, the scattering-bars (SBs) are more crucial than ever to ensure a good on-wafer printability of the line space pattern and hole pattern. The main pattern with small pitches requires a very narrow PV (process variation) band. A delicate SB addition scheme is thus needed to maintain a sufficient PW (process window) for the semi-iso- and iso-patterns. In general, the wider, longer, and closer to main feature SBs will be more effective in enhancing the printability; on the other hand, they are also more likely to be printed on the wafer; resulting in undesired defects transferable to subsequent processes. In this work, we have developed a model based approach for the scattering-bar printing avoidance (SPA). A specially designed optical model was tuned based on a broad range of test patterns which contain a variation of CDs and SB placements showing printing and non-printing scattering bars. A printing threshold is then obtained to check the extra-printings of SBs. The accuracy of this threshold is verified by pre-designed test patterns. The printing threshold associated with our novel SPA model allows us to set up a proper SB rule.
NASA Astrophysics Data System (ADS)
Ng, H. B.; Shearwood, C.
2007-12-01
The successful development of micro-needles can help transport drugs and vaccines both effectively and painlessly across the skin. However, not all micro-needles are strong enough to withstand the insertion forces and viscoelasticity of the skin. The work here focuses on the micro-fabrication of high aspect ratio needles with careful control of needle-profile using dry etching technologies. Silicon micro-needles, 150μm in length with base-diameters ranging from 90 to 240μm have been investigated in this study. A novel, multiple-sacrificial approach has been demonstrated as suited to the fabrication of long micro-needle bodies with positive profiles. The parameters that control the isotropic etching are adjusted to control the ratio of the needle-base diameter to needle length. By careful control of geometry, the needle profile can be engineered to give a suitable tip size for penetration, as well as a broad needle base to facilitate the creation of either single or multiple-through holes. This approach allows the mechanical properties of the otherwise brittle needles to be optimized. Finite element analysis indicates that the micro-needles will fracture prematurely due to buckling, with forces ranging from 10 to 30mN.
NASA Astrophysics Data System (ADS)
Ginzburg, D.; Knafo, Y.; Manor, A.; Seif, R.; Ghelman, M.; Ellenbogen, M.; Pushkarsky, V.; Ifergan, Y.; Semyonov, N.; Wengrowicz, U.; Mazor, T.; Kadmon, Y.; Cohen, Y.; Osovizky, A.
2015-06-01
There is a need to develop new personal radiation detector (PRD) technologies that can be mass produced. On August 2013, DARPA released a request for information (RFI) seeking innovative radiation detection technologies. In addition, on December 2013, a Broad Agency Announcement (BAA) for the SIGMA program was released. The RFI requirements focused on a sensor that should possess three main properties: low cost, high compactness and radioisotope identification capabilities. The identification performances should facilitate the detection of a hidden threat, ranging from special nuclear materials (SNM) to commonly used radiological sources. Subsequently, the BAA presented the specific requirements at an instrument level and provided a comparison between the current market status (state-of-the-art) and the SIGMA program objectives. This work presents an optional alternative for both the detection technology (sensor with communication output and without user interface) for DARPA's initial RFI and for the PRD required by the SIGMA program. A broad discussion is dedicated to the method proposed to fulfill the program objectives and to the selected alternative that is based on the PDS-GO design and technology. The PDS-GO is the first commercially available PRD that is based on a scintillation crystal optically coupled with a silicon photomultiplier (SiPM), a solid-state light sensor. This work presents the current performance of the instrument and possible future upgrades based on recent technological improvements in the SiPM design. The approach of utilizing the SiPM with a commonly available CsI(Tl) crystal is the key for achieving the program objectives. This approach provides the appropriate performance, low cost, mass production and small dimensions; however, it requires a creative approach to overcome the obstacles of the solid-state detector dark current (noise) and gain stabilization over a wide temperature range. Based on the presented results, we presume that the proposed approach of SiPM, with pixel size of 35 μm, coupled to a scintillation material (for gamma and neutron detection) ensures the availability and low cost of the key components. Furthermore, automated manufacturing process enables mass production, thereby fulfilling the SIGMA program requirements, both as a sensor (assimilated with mobile device) and as a full detection device.
Can We Practically Bring Physics-based Modeling Into Operational Analytics Tools?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Granderson, Jessica; Bonvini, Marco; Piette, Mary Ann
We present that analytics software is increasingly used to improve and maintain operational efficiency in commercial buildings. Energy managers, owners, and operators are using a diversity of commercial offerings often referred to as Energy Information Systems, Fault Detection and Diagnostic (FDD) systems, or more broadly Energy Management and Information Systems, to cost-effectively enable savings on the order of ten to twenty percent. Most of these systems use data from meters and sensors, with rule-based and/or data-driven models to characterize system and building behavior. In contrast, physics-based modeling uses first-principles and engineering models (e.g., efficiency curves) to characterize system and buildingmore » behavior. Historically, these physics-based approaches have been used in the design phase of the building life cycle or in retrofit analyses. Researchers have begun exploring the benefits of integrating physics-based models with operational data analytics tools, bridging the gap between design and operations. In this paper, we detail the development and operator use of a software tool that uses hybrid data-driven and physics-based approaches to cooling plant FDD and optimization. Specifically, we describe the system architecture, models, and FDD and optimization algorithms; advantages and disadvantages with respect to purely data-driven approaches; and practical implications for scaling and replicating these techniques. Finally, we conclude with an evaluation of the future potential for such tools and future research opportunities.« less
Hybrid Orientation Based Human Limbs Motion Tracking Method
Glonek, Grzegorz; Wojciechowski, Adam
2017-01-01
One of the key technologies that lays behind the human–machine interaction and human motion diagnosis is the limbs motion tracking. To make the limbs tracking efficient, it must be able to estimate a precise and unambiguous position of each tracked human joint and resulting body part pose. In recent years, body pose estimation became very popular and broadly available for home users because of easy access to cheap tracking devices. Their robustness can be improved by different tracking modes data fusion. The paper defines the novel approach—orientation based data fusion—instead of dominating in literature position based approach, for two classes of tracking devices: depth sensors (i.e., Microsoft Kinect) and inertial measurement units (IMU). The detailed analysis of their working characteristics allowed to elaborate a new method that let fuse more precisely limbs orientation data from both devices and compensates their imprecisions. The paper presents the series of performed experiments that verified the method’s accuracy. This novel approach allowed to outperform the precision of position-based joints tracking, the methods dominating in the literature, of up to 18%. PMID:29232832
Tao, Yunwen; Zou, Wenli; Cremer, Dieter; Kraka, Elfi
2017-10-26
A novel approach is presented to assess chemical similarity based the local vibrational mode analysis developed by Konkoli and Cremer. The local mode frequency shifts are introduced as similarity descriptors that are sensitive to any electronic structure change. In this work, 59 different monosubstituted benzenes are compared. For a subset of 43 compounds, for which experimental data was available, the ortho-/para- and meta-directing effect in electrophilic aromatic substitution reactions could be correctly reproduced, proving the robustness of the new similarity index. For the remaining 16 compounds, the directing effect was predicted. The new approach is broadly applicable to all compounds for which either experimental or calculated vibrational frequency information is available.
Moving research beyond the spanking debate.
MacMillan, Harriet L; Mikton, Christopher R
2017-09-01
Despite numerous studies identifying a broad range of harms associated with the use of spanking and other types of physical punishment, debate continues about its use as a form of discipline. In this commentary, we recommend four strategies to move the field forward and beyond the spanking debate including: 1) use of methodological approaches that allow for stronger causal inference; 2) consideration of human rights issues; 3) a focus on understanding the causes of spanking and reasons for its decline in certain countries; and 4) more emphasis on evidence-based approaches to changing social norms to reject spanking as a form of discipline. Physical punishment needs to be recognized as an important public health problem. Copyright © 2017 Elsevier Ltd. All rights reserved.
THE RIGHT TO SUTURES: SOCIAL EPIDEMIOLOGY, HUMAN RIGHTS, AND SOCIAL JUSTICE
Venkatapuram, Sridhar; Bell, Ruth; Marmot, Michael
2013-01-01
The article examines the convergences and contrasts between social epidemiology, social medicine, and human rights approaches toward advancing global health and health equity. The first section describes the goals and work of the WHO Commission on Social Determinants of Health. The second section discusses the role of human rights in the Commission’s work. The third section evaluates, from the perspective of social epidemiology, two rights-based approaches to advancing health and health equity as compared to a view that focuses more broadly on social justice. The concluding section identifies four areas where social epidemiologists, practitioners of social medicine, and health and human rights advocates can and must work together in order to make progress on health and health equity. PMID:21178186
DOE Office of Scientific and Technical Information (OSTI.GOV)
Juffmann, Thomas; Koppell, Stewart A.; Klopfer, Brannon B.
Feynman once asked physicists to build better electron microscopes to be able to watch biology at work. While electron microscopes can now provide atomic resolution, electron beam induced specimen damage precludes high resolution imaging of sensitive materials, such as single proteins or polymers. Here, we use simulations to show that an electron microscope based on a multi-pass measurement protocol enables imaging of single proteins, without averaging structures over multiple images. While we demonstrate the method for particular imaging targets, the approach is broadly applicable and is expected to improve resolution and sensitivity for a range of electron microscopy imaging modalities,more » including, for example, scanning and spectroscopic techniques. The approach implements a quantum mechanically optimal strategy which under idealized conditions can be considered interaction-free.« less
Model selection for anomaly detection
NASA Astrophysics Data System (ADS)
Burnaev, E.; Erofeev, P.; Smolyakov, D.
2015-12-01
Anomaly detection based on one-class classification algorithms is broadly used in many applied domains like image processing (e.g. detection of whether a patient is "cancerous" or "healthy" from mammography image), network intrusion detection, etc. Performance of an anomaly detection algorithm crucially depends on a kernel, used to measure similarity in a feature space. The standard approaches (e.g. cross-validation) for kernel selection, used in two-class classification problems, can not be used directly due to the specific nature of a data (absence of a second, abnormal, class data). In this paper we generalize several kernel selection methods from binary-class case to the case of one-class classification and perform extensive comparison of these approaches using both synthetic and real-world data.
Evaluation of Genetic Algorithm Concepts using Model Problems. Part 1; Single-Objective Optimization
NASA Technical Reports Server (NTRS)
Holst, Terry L.; Pulliam, Thomas H.
2003-01-01
A genetic-algorithm-based optimization approach is described and evaluated using a simple hill-climbing model problem. The model problem utilized herein allows for the broad specification of a large number of search spaces including spaces with an arbitrary number of genes or decision variables and an arbitrary number hills or modes. In the present study, only single objective problems are considered. Results indicate that the genetic algorithm optimization approach is flexible in application and extremely reliable, providing optimal results for all problems attempted. The most difficult problems - those with large hyper-volumes and multi-mode search spaces containing a large number of genes - require a large number of function evaluations for GA convergence, but they always converge.
An approach to quality and security of supply for single-use bioreactors.
Barbaroux, Magali; Gerighausen, Susanne; Hackel, Heiko
2014-01-01
Single-use systems (also referred to as disposables) have become a huge part of the bioprocessing industry, which raised concern in the industry regarding quality and security of supply. Processes must be in place to assure the supply and control of outsourced activities and quality of purchased materials along the product life cycle. Quality and security of supply for single-use bioreactors (SUBs) are based on a multidisciplinary approach. Developing a state-of-the-art SUB-system based on quality by design (QbD) principles requires broad expertise and know-how including the cell culture application, polymer chemistry, regulatory requirements, and a deep understanding of the biopharmaceutical industry. Using standardized products reduces the complexity and strengthens the robustness of the supply chain. Well-established supplier relations including risk mitigation strategies are the basis for achieving long-term security of supply. Well-developed quality systems including change control approaches aligned with the requirements of the biopharmaceutical industry are a key factor in supporting long-term product availability. This chapter outlines the approach to security of supply for key materials used in single-use production processes for biopharmaceuticals from a supplier perspective.
Science and society: some "made-in-Canada" options for improving integration.
Kosseim, Patricia; Chapman, Sheila
2011-05-01
In this article, the authors describe relatively recent efforts by scientific research agencies to promote, through various funding programs, the integration of social sciences and humanities with the natural sciences. This "integrated" approach seeks to study science through a broader interdisciplinary lens in order to better anticipate, understand, and address its ethical, legal, and social implications. The authors review the origins and evolution of this trend, as well the arguments which have been formulated by both proponents and critics of integration. By using Genome Canada's "GE(3)LS" Research Program as a case study, the authors discuss the successes and continuing challenges of this model based on evaluation results available to date. The authors then go on to examine and compare three possible models for improving the future success of the GE(3)LS research program, including: 1) enhancing the current integrated research approach through incremental refinements based on concrete evidence and lessons learned; 2) promoting greater interaction and synergy across GE(3)LS research projects through a deliberate, systematic and coordinated "hub and spoke" approach; and 3) taking a broad programmatic approach to GE(3)LS research by creating a central resource of available expertise and advisory capacity.
NASA Astrophysics Data System (ADS)
Selker, J. S.; Kahsai, S. K.
2017-12-01
Green Infrastructure (GI) or Low impact development (LID), is a land use planning and design approach with the objective of mitigating land development impacts to the environment, and is ever more looked to as a way to lessen runoff and pollutant loading to receiving water bodies. Broad-scale approaches for siting GI/LID have been developed for agricultural watersheds, but are rare for urban watersheds, largely due to greater land use complexity. And it is even more challenging when it comes to Urban Africa due to the combination of poor data quality, rapid and unplanned development, and civic institutions unable to reliably carry out regular maintenance. We present a spacio-temporal simulation-based approach to identify an optimal prioritization of sites for GI/LID based on DEM, land use and land cover. Optimization used is a multi-objective optimization tool along with an urban storm water management model (SWMM) to identify the most cost-effective combination of LID/GI. This was applied to an urban watershed in NW Kampala, Lubigi Catchment (notorious for being heavily flooded every year), with a miscellaneous use watershed in Uganda, as a case-study to demonstrate the approach.
Two decades of ART: improving on success through further research
HOLMGREN, Christopher J.; FIGUEREDO, Márcia Cançado
2009-01-01
ABSTRACT Since the introduction of the Atraumatic Restorative Treatment (ART) approach over twenty years ago, more than 190 research publications have appeared. The last research agenda defining research priorities for ART was published in 1999. The objective of the present work was to review existing research in the context of future research priorities for ART. Material and Methods: An internet survey was conducted amongst those who had published on ART or were known to be working on the ART approach, to solicit their views as to areas of future ART research. Three broad categories were defined, namely: 1. Basic and laboratory research; 2. Clinical research, and, 3. Community, Public Health, Health Services Research. Results: A 31% response rate was achieved. The study identified a number of new areas of research as well as areas where additional research is required. These are expressed as recommendations for future ART research. Conclusions: The ART approach is based on a robust, reliable and ever-growing evidence base concerning its clinical applications which indicates that it is a reliable and quality treatment approach. In common with all other oral health care procedures, targeted applied research is required to improve the oral health care offered. PMID:21499666
Using EMIS to Identify Top Opportunities for Commercial Building Efficiency
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, Guanjing; Singla, Rupam; Granderson, Jessica
Energy Management and Information Systems (EMIS) comprise a broad family of tools and services to manage commercial building energy use. These technologies offer a mix of capabilities to store, display, and analyze energy use and system data, and in some cases, provide control. EMIS technologies enable 10–20 percent site energy savings in best practice implementations. Energy Information System (EIS) and Fault Detection and Diagnosis (FDD) systems are two key technologies in the EMIS family. Energy Information Systems are broadly defined as the web-based software, data acquisition hardware, and communication systems used to analyze and display building energy performance. At amore » minimum, an EIS provides daily, hourly or sub-hourly interval meter data at the whole-building level, with graphical and analytical capability. Fault Detection and Diagnosis systems automatically identify heating, ventilation, and air-conditioning (HVAC) system or equipment-level performances issues, and in some cases are able to isolate the root causes of the problem. They use computer algorithms to continuously analyze system-level operational data to detect faults and diagnose their causes. Many FDD tools integrate the trend log data from a Building Automation System (BAS) but otherwise are stand-alone software packages; other types of FDD tools are implemented as “on-board” equipment-embedded diagnostics. (This document focuses on the former.) Analysis approaches adopted in FDD technologies span a variety of techniques from rule-based methods to process history-based approaches. FDD tools automate investigations that can be conducted via manual data inspection by someone with expert knowledge, thereby expanding accessibility and breath of analysis opportunity, and also reducing complexity.« less
NASA Astrophysics Data System (ADS)
Tzanavaris, Panayiotis
Fluorescent Fe K emission from neutral matter in AGN spectracan arise in the accretion disk around the centralsupermassive black hole [SMBH] ("broad" line) and/or in distant matter ("narrow"line). If it is broad, it provides a unique windowto the strong gravity SMBH regime, including information on SMBH spin;if it is narrow, it probesthe distant reprocessor, likely a clumpy torus. We will use broadband X-ray data from four NASA X-ray missionsfor 45 nearby AGNs, and 1. Assess whether any known "broad" relativistic lines can be modeledas "narrow"instead, by means of self-consistent modeling of fluorescence,direct, and scattered continua; 2. Measure absorbing column densities both in and out of the line of sight; 3. Bootstrap measures of intrinsic bolometric AGN luminosity, with X-ray and optical data. This work will provide updated results on a) black hole spin, with implications on AGN jet power and accretion history; b) the census of highly-obscured (Compton thick) vs. Compton thin AGNs, with implications on models of the Cosmic X-ray Background; c) calibrations of Fe K line, X-ray intrinsic continuum, [OIII] and [OIV] luminosities as measures of intrinsc bolometric AGN luminosity, with implications on AGN feedback and galaxy evolution. Key in our approach is a physically based, self-consistent modeling of the narrow line, with finite column density in and out of the line of sight, and the latest relativistic modeling of the broad line.
Barazzetti, Gaia; Cavalli, Samuele; Benaroyo, Lazare; Kaufmann, Alain
2017-03-01
Informed consent and return of research results are among the most debated topics in the biobank literature. We discuss ethical, social, and policy issues associated with returning results in the context of biobanks using a broad consent approach, in the light of data from a qualitative survey of citizens' and physicians' views. Data were collected through interviews and focus groups to investigate stakeholders' perspectives about a large-scale hospital-based biobank designed to foster biomedical research, including prospective genomics research, and "personalized" medicine. Both physicians and citizens considered psychosocial impacts as crucial in the assessment of benefits expected from a return of results to biobank participants. In particular, physicians highlighted the possible consequences on the patient-doctor relationship and discussed implications for the concept of "personalized" medicine. Citizens held ambivalent attitudes toward returning individual research results: they defended the "right not to know," while they also considered a sort of "responsibility to know" because of potential implications of results for family members. Moreover, physicians and citizens raised questions about the broad consent model used for inhospital biobank recruitment and expressed their needs for more training in genomics and more information on the biobank initiative. Stakeholders such as citizens and physicians, who may be concerned as potential biobank participants or as healthcare professionals involved in the management of clinically relevant research results, provide useful insights into several aspects of broad consent and return of results, related in particular to the interface between research and the clinic.
Giftedness and Cultural Accumulation: An Information Processing Perspective
ERIC Educational Resources Information Center
Woolcott, Geoff
2013-01-01
There appears to be differing approaches, in modern education, to the identification and development of gifted students, but researchers are beginning to find some cohesiveness through approaches that examine giftedness from within broad views of human cognition and behavior. This paper takes such an approach by considering learning and memory as…
The Managerial Approach to Tertiary Education: A Critical Analysis.
ERIC Educational Resources Information Center
Baron, Bernard
The various elements of the management approach to tertiary education (broadly, all institutions of further and higher education maintained by local authorities) are identified, with the principal focus on the general approach known as "Management by Objectives" (MBO). The arguments for and against its use and possible hazards following…
Chiropractic management of low back disorders: report from a consensus process.
Globe, Gary A; Morris, Craig E; Whalen, Wayne M; Farabaugh, Ronald J; Hawk, Cheryl
2008-01-01
Although a number of guidelines addressing manipulation, an important component of chiropractic professional care, exist, none to date have incorporated a broad-based consensus of chiropractic research and clinical experts representing mainstream chiropractic practice into a practical document designed to provide standardized parameters of care. The purpose of this project was to develop such a document. Development of the document began with seed materials, from which seed statements were distilled. These were circulated electronically to the Delphi panel until consensus was reached, which was considered to be present when there was agreement by at least 80% of the panelists. The panel consisted of 40 clinically experienced doctors of chiropractic, representing 15 chiropractic colleges and 16 states, as well as both the American Chiropractic Association and the International Chiropractic Association. The panel reached 80% consensus of the 27 seed statements after 2 rounds. Specific recommendations regarding treatment frequency and duration, as well as outcome assessment and contraindications for manipulation were agreed upon by the panel. A broad-based panel of experienced chiropractors was able to reach a high level (80%) of consensus regarding specific aspects of the chiropractic approach to care for patients with low back pain, based on both the scientific evidence and their clinical experience.
Werner, James J; Stange, Kurt C
2014-01-01
Practice-based research networks (PBRNs) have developed a grounded approach to conducting practice-relevant and translational research in community practice settings. Seismic shifts in the health care landscape are shaping PBRNs that work across organizational and institutional margins to address complex problems. Praxis-based research networks combine PBRN knowledge generation with multistakeholder learning, experimentation, and application of practical knowledge. The catalytic processes in praxis-based research networks are cycles of action and reflection based on experience, observation, conceptualization, and experimentation by network members and partners. To facilitate co-learning and solution-building, these networks have a flexible architecture that allows pragmatic inclusion of stakeholders based on the demands of the problem and the needs of the network. Praxis-based research networks represent an evolving trend that combines the core values of PBRNs with new opportunities for relevance, rigor, and broad participation. © Copyright 2014 by the American Board of Family Medicine.
Elberling, Claus; Don, Manuel
2010-01-01
A recent study evaluates auditory brainstem responses (ABRs) evoked by chirps of different durations (sweeping rates) [Elberling et al. (2010). J. Acoust. Soc. Am. 128, 215–223]. The study demonstrates that shorter chirps are most efficient at higher levels of stimulation whereas longer chirps are most efficient at lower levels. Mechanisms other than the traveling wave delay, in particular, upward spread of excitation and changes in cochlear-neural delay with level, are suggested to be responsible for these findings. As a consequence, delay models based on estimates of the traveling wave delay are insufficient for the design of chirp stimuli, and another delay model based on a direct approach is therefore proposed. The direct approach uses ABR-latencies from normal-hearing subjects in response to octave-band chirps over a wide range of levels. The octave-band chirps are constructed by decomposing a broad-band chirp, and constitute a subset of the chirp. The delay compensations of the proposed model are similar to those found in the previous experimental study, which thus verifies the results of the proposed model. PMID:21110591
Peptide Array X-Linking (PAX): A New Peptide-Protein Identification Approach
Okada, Hirokazu; Uezu, Akiyoshi; Soderblom, Erik J.; Moseley, M. Arthur; Gertler, Frank B.; Soderling, Scott H.
2012-01-01
Many protein interaction domains bind short peptides based on canonical sequence consensus motifs. Here we report the development of a peptide array-based proteomics tool to identify proteins directly interacting with ligand peptides from cell lysates. Array-formatted bait peptides containing an amino acid-derived cross-linker are photo-induced to crosslink with interacting proteins from lysates of interest. Indirect associations are removed by high stringency washes under denaturing conditions. Covalently trapped proteins are subsequently identified by LC-MS/MS and screened by cluster analysis and domain scanning. We apply this methodology to peptides with different proline-containing consensus sequences and show successful identifications from brain lysates of known and novel proteins containing polyproline motif-binding domains such as EH, EVH1, SH3, WW domains. These results suggest the capacity of arrayed peptide ligands to capture and subsequently identify proteins by mass spectrometry is relatively broad and robust. Additionally, the approach is rapid and applicable to cell or tissue fractions from any source, making the approach a flexible tool for initial protein-protein interaction discovery. PMID:22606326
Emerman, Amy B; Bowman, Sarah K; Barry, Andrew; Henig, Noa; Patel, Kruti M; Gardner, Andrew F; Hendrickson, Cynthia L
2017-07-05
Next-generation sequencing (NGS) is a powerful tool for genomic studies, translational research, and clinical diagnostics that enables the detection of single nucleotide polymorphisms, insertions and deletions, copy number variations, and other genetic variations. Target enrichment technologies improve the efficiency of NGS by only sequencing regions of interest, which reduces sequencing costs while increasing coverage of the selected targets. Here we present NEBNext Direct ® , a hybridization-based, target-enrichment approach that addresses many of the shortcomings of traditional target-enrichment methods. This approach features a simple, 7-hr workflow that uses enzymatic removal of off-target sequences to achieve a high specificity for regions of interest. Additionally, unique molecular identifiers are incorporated for the identification and filtering of PCR duplicates. The same protocol can be used across a wide range of input amounts, input types, and panel sizes, enabling NEBNext Direct to be broadly applicable across a wide variety of research and diagnostic needs. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.
Addressing the Challenges of Pathogen Evolution on the World's Arable Crops.
Burdon, Jeremy J; Zhan, Jiasui; Barrett, Luke G; Papaïx, Julien; Thrall, Peter H
2016-10-01
Advances in genomic and molecular technologies coupled with an increasing understanding of the fine structure of many resistance and infectivity genes, have opened up a new era of hope in controlling the many plant pathogens that continue to be a major source of loss in arable crops. Some new approaches are under consideration including the use of nonhost resistance and the targeting of critical developmental constraints. However, the major thrust of these genomic and molecular approaches is to enhance the identification of resistance genes, to increase their ease of manipulation through marker and gene editing technologies and to lock a range of resistance genes together in simply manipulable resistance gene cassettes. All these approaches essentially continue a strategy that assumes the ability to construct genetic-based resistance barriers that are insurmountable to target pathogens. Here we show how the recent advances in knowledge and marker technologies can be used to generate more durable disease resistance strategies that are based on broad evolutionary principles aimed at presenting pathogens with a shifting, landscape of fluctuating directional selection.
Rational design of aptazyme riboswitches for efficient control of gene expression in mammalian cells
Zhong, Guocai; Wang, Haimin; Bailey, Charles C; Gao, Guangping; Farzan, Michael
2016-01-01
Efforts to control mammalian gene expression with ligand-responsive riboswitches have been hindered by lack of a general method for generating efficient switches in mammalian systems. Here we describe a rational-design approach that enables rapid development of efficient cis-acting aptazyme riboswitches. We identified communication-module characteristics associated with aptazyme functionality through analysis of a 32-aptazyme test panel. We then developed a scoring system that predicts an aptazymes’s activity by integrating three characteristics of communication-module bases: hydrogen bonding, base stacking, and distance to the enzymatic core. We validated the power and generality of this approach by designing aptazymes responsive to three distinct ligands, each with markedly wider dynamic ranges than any previously reported. These aptayzmes efficiently regulated adeno-associated virus (AAV)-vectored transgene expression in cultured mammalian cells and mice, highlighting one application of these broadly usable regulatory switches. Our approach enables efficient, protein-independent control of gene expression by a range of small molecules. DOI: http://dx.doi.org/10.7554/eLife.18858.001 PMID:27805569
Santini, Luca; Cornulier, Thomas; Bullock, James M; Palmer, Stephen C F; White, Steven M; Hodgson, Jenny A; Bocedi, Greta; Travis, Justin M J
2016-07-01
Estimating population spread rates across multiple species is vital for projecting biodiversity responses to climate change. A major challenge is to parameterise spread models for many species. We introduce an approach that addresses this challenge, coupling a trait-based analysis with spatial population modelling to project spread rates for 15 000 virtual mammals with life histories that reflect those seen in the real world. Covariances among life-history traits are estimated from an extensive terrestrial mammal data set using Bayesian inference. We elucidate the relative roles of different life-history traits in driving modelled spread rates, demonstrating that any one alone will be a poor predictor. We also estimate that around 30% of mammal species have potential spread rates slower than the global mean velocity of climate change. This novel trait-space-demographic modelling approach has broad applicability for tackling many key ecological questions for which we have the models but are hindered by data availability. © 2016 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.
Three-Dimensional Computational Fluid Dynamics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Haworth, D.C.; O'Rourke, P.J.; Ranganathan, R.
1998-09-01
Computational fluid dynamics (CFD) is one discipline falling under the broad heading of computer-aided engineering (CAE). CAE, together with computer-aided design (CAD) and computer-aided manufacturing (CAM), comprise a mathematical-based approach to engineering product and process design, analysis and fabrication. In this overview of CFD for the design engineer, our purposes are three-fold: (1) to define the scope of CFD and motivate its utility for engineering, (2) to provide a basic technical foundation for CFD, and (3) to convey how CFD is incorporated into engineering product and process design.
Critical spaces for quasilinear parabolic evolution equations and applications
NASA Astrophysics Data System (ADS)
Prüss, Jan; Simonett, Gieri; Wilke, Mathias
2018-02-01
We present a comprehensive theory of critical spaces for the broad class of quasilinear parabolic evolution equations. The approach is based on maximal Lp-regularity in time-weighted function spaces. It is shown that our notion of critical spaces coincides with the concept of scaling invariant spaces in case that the underlying partial differential equation enjoys a scaling invariance. Applications to the vorticity equations for the Navier-Stokes problem, convection-diffusion equations, the Nernst-Planck-Poisson equations in electro-chemistry, chemotaxis equations, the MHD equations, and some other well-known parabolic equations are given.
Passive, Collapsible Contingency Urinal for Human Space Flight
NASA Technical Reports Server (NTRS)
Jenson, Ryan
2015-01-01
Fluid transport systems for spacecraft face acute challenges because of the persistently unfamiliar and unforgiving low-gravity environment. IRPI, LLC, has developed a contingency wastewater collection and processing device that provides passive liquid collation, containment, bubble separation, and droplet coalescence functions. The lightweight, low-volume, low-cost, and potentially disposable device may be used for subsequent sampling, metering, storage, disposal, and/or reuse. The approach includes a fractal wetting design that incorporates smart capillary fluidics. This work could have a broad impact on capillary-based fluid management on spacecraft and on Earth.
Policy model for space economy infrastructure
NASA Astrophysics Data System (ADS)
Komerath, Narayanan; Nally, James; Zilin Tang, Elizabeth
2007-12-01
Extraterrestrial infrastructure is key to the development of a space economy. Means for accelerating transition from today's isolated projects to a broad-based economy are considered. A large system integration approach is proposed. The beginnings of an economic simulation model are presented, along with examples of how interactions and coordination bring down costs. A global organization focused on space infrastructure and economic expansion is proposed to plan, coordinate, fund and implement infrastructure construction. This entity also opens a way to raise low-cost capital and solve the legal and public policy issues of access to extraterrestrial resources.
Different approaches to acute organophosphorus poison treatment.
Nurulain, Syed Muhammad
2012-07-01
Organophosphorus compounds (OPCs) have a wide variety of applications and are a serious threat for self-poisoning, unintentional misuse, terrorist attack, occupational hazard and warfare attack. The present standard treatment has been reported to be unsatisfactory. Many novel approaches are being used and tested for acute organophosphorus (OP) poison treatment. The bioscavenger concept captured high attention among the scientific community during the last few decades. Other approaches like alkalinisation of blood plasma/serum and use of weak inhibitors against strong inhibitors, though it showed promising results, did not get such wide attention. The introduction of a novel broad-spectrum oxime has also been in focus. In this mini-review, an update of the overview of four different approaches has been discussed. The standard therapy that is atropine+oxime+benzodiazepine along with supportive measures will continue to be the best option with only the replacement of a single oxime to improve its broad-spectrum efficacy.
Computational medicinal chemistry in fragment-based drug discovery: what, how and when.
Rabal, Obdulia; Urbano-Cuadrado, Manuel; Oyarzabal, Julen
2011-01-01
The use of fragment-based drug discovery (FBDD) has increased in the last decade due to the encouraging results obtained to date. In this scenario, computational approaches, together with experimental information, play an important role to guide and speed up the process. By default, FBDD is generally considered as a constructive approach. However, such additive behavior is not always present, therefore, simple fragment maturation will not always deliver the expected results. In this review, computational approaches utilized in FBDD are reported together with real case studies, where applicability domains are exemplified, in order to analyze them, and then, maximize their performance and reliability. Thus, a proper use of these computational tools can minimize misleading conclusions, keeping the credit on FBDD strategy, as well as achieve higher impact in the drug-discovery process. FBDD goes one step beyond a simple constructive approach. A broad set of computational tools: docking, R group quantitative structure-activity relationship, fragmentation tools, fragments management tools, patents analysis and fragment-hopping, for example, can be utilized in FBDD, providing a clear positive impact if they are utilized in the proper scenario - what, how and when. An initial assessment of additive/non-additive behavior is a critical point to define the most convenient approach for fragments elaboration.
On the sound insulation of acoustic metasurface using a sub-structuring approach
NASA Astrophysics Data System (ADS)
Yu, Xiang; Lu, Zhenbo; Cheng, Li; Cui, Fangsen
2017-08-01
The feasibility of using an acoustic metasurface (AMS) with acoustic stop-band property to realize sound insulation with ventilation function is investigated. An efficient numerical approach is proposed to evaluate its sound insulation performance. The AMS is excited by a reverberant sound source and the standardized sound reduction index (SRI) is numerically investigated. To facilitate the modeling, the coupling between the AMS and the adjacent acoustic fields is formulated using a sub-structuring approach. A modal based formulation is applied to both the source and receiving room, enabling an efficient calculation in the frequency range from 125 Hz to 2000 Hz. The sound pressures and the velocities at the interface are matched by using a transfer function relation based on ;patches;. For illustration purposes, numerical examples are investigated using the proposed approach. The unit cell constituting the AMS is constructed in the shape of a thin acoustic chamber with tailored inner structures, whose stop-band property is numerically analyzed and experimentally demonstrated. The AMS is shown to provide effective sound insulation of over 30 dB in the stop-band frequencies from 600 to 1600 Hz. It is also shown that the proposed approach has the potential to be applied to a broad range of AMS studies and optimization problems.
Brown, Katherine; Barrett, Hazel
2013-01-01
With increased migration, female genital mutilation (FGM) also referred to as female circumcision or female genital cutting is no longer restricted to Africa, the Middle East, and Asia. The European Parliament estimates that up to half a million women living in the EU have been subjected to FGM, with a further 180,000 at risk. Aware of the limited success of campaigns addressing FGM, the World Health Organization recommended a behavioural change approach be implemented in order to end FGM. To date, however, little progress has been made in adopting a behaviour change approach in strategies aimed at ending FGM. Based on research undertaken as part of the EU's Daphne III programme, which researched FGM intervention programmes linked to African communities in the EU (REPLACE), this paper argues that behaviour change has not been implemented due to a lack of understanding relating to the application of the two broad categories of behaviour change approach: individualistic decision-theoretic and community-change game-theoretic approaches, and how they may be integrated to aid our understanding and the development of future intervention strategies. We therefore discuss how these can be integrated and implemented using community-based participatory action research methods with affected communities. PMID:23983698
DOE Office of Scientific and Technical Information (OSTI.GOV)
Moges, Edom; Demissie, Yonas; Li, Hong-Yi
2016-04-01
In most water resources applications, a single model structure might be inadequate to capture the dynamic multi-scale interactions among different hydrological processes. Calibrating single models for dynamic catchments, where multiple dominant processes exist, can result in displacement of errors from structure to parameters, which in turn leads to over-correction and biased predictions. An alternative to a single model structure is to develop local expert structures that are effective in representing the dominant components of the hydrologic process and adaptively integrate them based on an indicator variable. In this study, the Hierarchical Mixture of Experts (HME) framework is applied to integratemore » expert model structures representing the different components of the hydrologic process. Various signature diagnostic analyses are used to assess the presence of multiple dominant processes and the adequacy of a single model, as well as to identify the structures of the expert models. The approaches are applied for two distinct catchments, the Guadalupe River (Texas) and the French Broad River (North Carolina) from the Model Parameter Estimation Experiment (MOPEX), using different structures of the HBV model. The results show that the HME approach has a better performance over the single model for the Guadalupe catchment, where multiple dominant processes are witnessed through diagnostic measures. Whereas, the diagnostics and aggregated performance measures prove that French Broad has a homogeneous catchment response, making the single model adequate to capture the response.« less
Bacterial fatty acid metabolism in modern antibiotic discovery.
Yao, Jiangwei; Rock, Charles O
2017-11-01
Bacterial fatty acid synthesis is essential for many pathogens and different from the mammalian counterpart. These features make bacterial fatty acid synthesis a desirable target for antibiotic discovery. The structural divergence of the conserved enzymes and the presence of different isozymes catalyzing the same reactions in the pathway make bacterial fatty acid synthesis a narrow spectrum target rather than the traditional broad spectrum target. Furthermore, bacterial fatty acid synthesis inhibitors are single-targeting, rather than multi-targeting like traditional monotherapeutic, broad-spectrum antibiotics. The single-targeting nature of bacterial fatty acid synthesis inhibitors makes overcoming fast-developing, target-based resistance a necessary consideration for antibiotic development. Target-based resistance can be overcome through multi-targeting inhibitors, a cocktail of single-targeting inhibitors, or by making the single targeting inhibitor sufficiently high affinity through a pathogen selective approach such that target-based mutants are still susceptible to therapeutic concentrations of drug. Many of the pathogens requiring new antibiotic treatment options encode for essential bacterial fatty acid synthesis enzymes. This review will evaluate the most promising targets in bacterial fatty acid metabolism for antibiotic therapeutics development and review the potential and challenges in advancing each of these targets to the clinic and circumventing target-based resistance. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016 Elsevier B.V. All rights reserved.
Park, Eunyoung; Lee, Cheonghoon; Bisesi, Michael; Lee, Jiyoung
2014-03-01
The disinfection efficiency of peracetic acid (PAA) was investigated on three microbial types using three different methods (filtration-based ATP (adenosine-triphosphate) bioluminescence, quantitative polymerase chain reaction (qPCR), culture-based method). Fecal indicator bacteria (Enterococcus faecium), virus indicator (male-specific (F(+)) coliphages (coliphages)), and protozoa disinfection surrogate (Bacillus subtilis spores (spores)) were tested. The mode of action for spore disinfection was visualized using scanning electron microscopy. The results indicated that PAA concentrations of 5 ppm (contact time: 5 min), 50 ppm (10 min), and 3,000 ppm (5 min) were needed to achieve 3-log reduction of E. faecium, coliphages, and spores, respectively. Scanning electron microscopy observation showed that PAA targets the external layers of spores. The lower reduction rates of tested microbes measured with qPCR suggest that qPCR may overestimate the surviving microbes. Collectively, PAA showed broad disinfection efficiency (susceptibility: E. faecium > coliphages > spores). For E. faecium and spores, ATP bioluminescence was substantially faster (∼5 min) than culture-based method (>24 h) and qPCR (2-3 h). This study suggests PAA as an effective alternative to inactivate broad types of microbial contaminants in water. Together with the use of rapid detection methods, this approach can be useful for urgent situations when timely response is needed for ensuring water quality.
The concept of resilience in OSH management: a review of approaches
Pęciłło, Małgorzata
2016-01-01
The concept of resilience has become very popular, especially in the 21st century. This concept is applicable to many fields, from mechanics to a broad range of social sciences. Resilience has even become part of the national and global policies of the USA, the United Nations and the European Commission. The concept of resilience has also been implemented in the area of safety and health based on the criticism of the traditional approach to occupational safety and health, which does not result in a satisfactory level of occupational safety. The concept of resilience was adopted to research occupational safety and health in different fields and thus with different approaches, such as via socio-technical studies, the psychological and behavioral aspects of organizational resilience and the link with research on individual or family resilience and its influence on work. PMID:26652938
Integration of prior knowledge into dense image matching for video surveillance
NASA Astrophysics Data System (ADS)
Menze, M.; Heipke, C.
2014-08-01
Three-dimensional information from dense image matching is a valuable input for a broad range of vision applications. While reliable approaches exist for dedicated stereo setups they do not easily generalize to more challenging camera configurations. In the context of video surveillance the typically large spatial extent of the region of interest and repetitive structures in the scene render the application of dense image matching a challenging task. In this paper we present an approach that derives strong prior knowledge from a planar approximation of the scene. This information is integrated into a graph-cut based image matching framework that treats the assignment of optimal disparity values as a labelling task. Introducing the planar prior heavily reduces ambiguities together with the search space and increases computational efficiency. The results provide a proof of concept of the proposed approach. It allows the reconstruction of dense point clouds in more general surveillance camera setups with wider stereo baselines.
Person-centred services? Rhetoric versus reality.
Joyce, Catherine
2017-04-01
National and jurisdictional governments are increasingly using commissioning in health and community services. This includes the devolution of functions such as service planning, resource allocation, and regionalised approaches to intake and service delivery, to non-government organisations. The aims of this paper are to reflect on the experiences of commissioning as a not-for-profit health provider, and to identify some important early lessons. This analysis highlights the importance of a rights-based approach in which consumers, carers and communities actively participate in the design, implementation and evaluation of service systems, not just individual service needs; and that pays special attention to the most disadvantaged and the most vulnerable. The mechanisms and approaches used by cohealth to implement these principles are described. Service users need to be supported to develop advocacy capacity individually and collectively, in order to make informed choices about their own service needs and about the system more broadly, to ensure accessible and appropriate services.
Solar steam generation by heat localization.
Ghasemi, Hadi; Ni, George; Marconnet, Amy Marie; Loomis, James; Yerci, Selcuk; Miljkovic, Nenad; Chen, Gang
2014-07-21
Currently, steam generation using solar energy is based on heating bulk liquid to high temperatures. This approach requires either costly high optical concentrations leading to heat loss by the hot bulk liquid and heated surfaces or vacuum. New solar receiver concepts such as porous volumetric receivers or nanofluids have been proposed to decrease these losses. Here we report development of an approach and corresponding material structure for solar steam generation while maintaining low optical concentration and keeping the bulk liquid at low temperature with no vacuum. We achieve solar thermal efficiency up to 85% at only 10 kW m(-2). This high performance results from four structure characteristics: absorbing in the solar spectrum, thermally insulating, hydrophilic and interconnected pores. The structure concentrates thermal energy and fluid flow where needed for phase change and minimizes dissipated energy. This new structure provides a novel approach to harvesting solar energy for a broad range of phase-change applications.
Sundaram, S K; Sacksteder, Colette A; Weber, Thomas J; Riley, Brian J; Addleman, R Shane; Harrer, Bruce J; Peterman, John W
2013-01-01
A significant challenge to realize the full potential of nanotechnology for therapeutic and diagnostic applications is to understand and evaluate how live cells interact with an external stimulus, such as a nanosized particle, and the toxicity and broad risk associated with these stimuli. It is difficult to capture the complexity and dynamics of these interactions by following omics-based approaches exclusively, which can be expensive and time-consuming. Attenuated total reflectance-Fourier transform infrared spectroscopy is well suited to provide noninvasive live-cell monitoring of cellular responses to potentially toxic nanosized particles or other stimuli. This alternative approach provides the ability to carry out rapid toxicity screenings and nondisruptive monitoring of live-cell cultures. We review the technical basis of the approach, the instrument configuration and interface with the biological media, the various effects that impact the data, subsequent data analysis and toxicity, and present some preliminary results on live-cell monitoring.
Preconditioning strategies for nonlinear conjugate gradient methods, based on quasi-Newton updates
NASA Astrophysics Data System (ADS)
Andrea, Caliciotti; Giovanni, Fasano; Massimo, Roma
2016-10-01
This paper reports two proposals of possible preconditioners for the Nonlinear Conjugate Gradient (NCG) method, in large scale unconstrained optimization. On one hand, the common idea of our preconditioners is inspired to L-BFGS quasi-Newton updates, on the other hand we aim at explicitly approximating in some sense the inverse of the Hessian matrix. Since we deal with large scale optimization problems, we propose matrix-free approaches where the preconditioners are built using symmetric low-rank updating formulae. Our distinctive new contributions rely on using information on the objective function collected as by-product of the NCG, at previous iterations. Broadly speaking, our first approach exploits the secant equation, in order to impose interpolation conditions on the objective function. In the second proposal we adopt and ad hoc modified-secant approach, in order to possibly guarantee some additional theoretical properties.
Fluorescence imaging of chromosomal DNA using click chemistry
NASA Astrophysics Data System (ADS)
Ishizuka, Takumi; Liu, Hong Shan; Ito, Kenichiro; Xu, Yan
2016-09-01
Chromosome visualization is essential for chromosome analysis and genetic diagnostics. Here, we developed a click chemistry approach for multicolor imaging of chromosomal DNA instead of the traditional dye method. We first demonstrated that the commercially available reagents allow for the multicolor staining of chromosomes. We then prepared two pro-fluorophore moieties that served as light-up reporters to stain chromosomal DNA based on click reaction and visualized the clear chromosomes in multicolor. We applied this strategy in fluorescence in situ hybridization (FISH) and identified, with high sensitivity and specificity, telomere DNA at the end of the chromosome. We further extended this approach to observe several basic stages of cell division. We found that the click reaction enables direct visualization of the chromosome behavior in cell division. These results suggest that the technique can be broadly used for imaging chromosomes and may serve as a new approach for chromosome analysis and genetic diagnostics.
Review of broad-scale drought monitoring of forests: Toward an integrated data mining approach
Steve Norman; Frank H. Koch; William W. Hargrove
2016-01-01
Efforts to monitor the broad-scale impacts of drought on forests often come up short. Drought is a direct stressor of forests as well as a driver of secondary disturbance agents, making a full accounting of drought impacts challenging. General impacts can be inferred from moisture deficits quantified using precipitation and temperature measurements. However,...
ERIC Educational Resources Information Center
Maringe, Felix; Masinire, Alfred; Nkambule, Thabisile
2015-01-01
Multiple deprivation affects a large proportion of schools in South Africa. The past 20 years of democracy have tended to focus on reforming education through curricula revision and a raft of redress-directed interventions, through the application of what we call a broad-brush policy approach. The paper argues that a broad-brush policy application…
Challenges in recovering resources from acid mine drainage
Nordstrom, D. Kirk; Bowell, Robert J.; Campbell, Kate M.; Alpers, Charles N.
2017-01-01
Metal recovery from mine waters and effluents is not a new approach but one that has occurred largely opportunistically over the last four millennia. Due to the need for low-cost resources and increasingly stringent environmental conditions, mine waters are being considered in a fresh light with a designed, deliberate approach to resource recovery often as part of a larger water treatment evaluation. Mine water chemistry is highly dependent on many factors including geology, ore deposit composition and mineralogy, mining methods, climate, site hydrology, and others. Mine waters are typically Ca-Mg-SO4±Al±Fe with a broad range in pH and metal content. The main issue in recovering components of these waters having potential economic value, such as base metals or rare earth elements, is the separation of these from more reactive metals such as Fe and Al. Broad categories of methods for separating and extracting substances from acidic mine drainage are chemical and biological. Chemical methods include solution, physicochemical, and electrochemical technologies. Advances in membrane techniques such as reverse osmosis have been substantial and the technique is both physical and chemical. Biological methods may be further divided into microbiological and macrobiological, but only the former is considered here as a recovery method, as the latter is typically used as a passive form of water treatment.
Kipke, Michele D.; Kubicek, Katrina; Supan, Jocelyn; Weiss, George; Schrager, Sheree
2012-01-01
African American young men who have sex with men (AAYMSM) represent the largest proportion of new HIV infections among MSM. While evidence-based interventions are lacking, all too often HIV interventions are implemented in a community without thoroughly understanding its needs, risks and assets. AAYMSM are not homogenous; subgroups exist that may require different approaches to be effective. The House and Ball communities represent one such subgroup. A community-engaged, mixed-methods approach was used. Participant observations, qualitative interviews (N=26), and a survey at House/Ball events (N=252) were completed. Survey data broadly describe the community. For example: 69% of survey respondents identify as gay; 25% as bisexual; 13% reported recent use of ecstasy and 11% recently participated in sex exchange. The depth of qualitative data is key for intervention development. For example, while the survey provides broad descriptions of respondents’ involvement in the House and Ball communities, leaders provided in-depth descriptions of the structure of the House and Ball scene –something vital to the development of HIV prevention programs within these communities. This kind of rigorous study is recommended prior to implementing an intervention. Findings are discussed in relation to leveraging the communities’ supportive aspects to design culturally relevant HIV prevention programs. PMID:22699855
Knowledge-based nonuniform sampling in multidimensional NMR.
Schuyler, Adam D; Maciejewski, Mark W; Arthanari, Haribabu; Hoch, Jeffrey C
2011-07-01
The full resolution afforded by high-field magnets is rarely realized in the indirect dimensions of multidimensional NMR experiments because of the time cost of uniformly sampling to long evolution times. Emerging methods utilizing nonuniform sampling (NUS) enable high resolution along indirect dimensions by sampling long evolution times without sampling at every multiple of the Nyquist sampling interval. While the earliest NUS approaches matched the decay of sampling density to the decay of the signal envelope, recent approaches based on coupled evolution times attempt to optimize sampling by choosing projection angles that increase the likelihood of resolving closely-spaced resonances. These approaches employ knowledge about chemical shifts to predict optimal projection angles, whereas prior applications of tailored sampling employed only knowledge of the decay rate. In this work we adapt the matched filter approach as a general strategy for knowledge-based nonuniform sampling that can exploit prior knowledge about chemical shifts and is not restricted to sampling projections. Based on several measures of performance, we find that exponentially weighted random sampling (envelope matched sampling) performs better than shift-based sampling (beat matched sampling). While shift-based sampling can yield small advantages in sensitivity, the gains are generally outweighed by diminished robustness. Our observation that more robust sampling schemes are only slightly less sensitive than schemes highly optimized using prior knowledge about chemical shifts has broad implications for any multidimensional NMR study employing NUS. The results derived from simulated data are demonstrated with a sample application to PfPMT, the phosphoethanolamine methyltransferase of the human malaria parasite Plasmodium falciparum.
Large-area Soil Moisture Surveys Using a Cosmic-ray Rover: Approaches and Results from Australia
NASA Astrophysics Data System (ADS)
Hawdon, A. A.; McJannet, D. L.; Renzullo, L. J.; Baker, B.; Searle, R.
2017-12-01
Recent improvements in satellite instrumentation has increased the resolution and frequency of soil moisture observations, and this in turn has supported the development of higher resolution land surface process models. Calibration and validation of these products is restricted by the mismatch of scales between remotely sensed and contemporary ground based observations. Although the cosmic ray neutron soil moisture probe can provide estimates soil moisture at a scale useful for the calibration and validation purposes, it is spatially limited to a single, fixed location. This scaling issue has been addressed with the development of mobile soil moisture monitoring systems that utilizes the cosmic ray neutron method, typically referred to as a `rover'. This manuscript describes a project designed to develop approaches for undertaking rover surveys to produce soil moisture estimates at scales comparable to satellite observations and land surface process models. A custom designed, trailer-mounted rover was used to conduct repeat surveys at two scales in the Mallee region of Victoria, Australia. A broad scale survey was conducted at 36 x 36 km covering an area of a standard SMAP pixel and an intensive scale survey was conducted over a 10 x 10 km portion of the broad scale survey, which is at a scale equivalent to that used for national water balance modelling. We will describe the design of the rover, the methods used for converting neutron counts into soil moisture and discuss factors controlling soil moisture variability. We found that the intensive scale rover surveys produced reliable soil moisture estimates at 1 km resolution and the broad scale at 9 km resolution. We conclude that these products are well suited for future analysis of satellite soil moisture retrievals and finer scale soil moisture models.
[Animals and environmentalist ethics].
Guichet, Jean-Luc
2013-01-01
While environmental ethics and animal ethics have a common source of inspiration, they do not agree on the question of the status of animals. Environmental ethicists criticise the narrowness of the reason, focused on pain, given by animal ethicists and their strictly individual point of view; they maintain that their ethical concept is less emotional and more informed by science, with a broad point of view taking natural networks into account. Animal ethicists respond critically, accusing the environmental ethicists of not having any ethical foundation. There are, however, prospects for reconciling the two approaches, provided that they recognise two different ethical stances for animals: one based on the integrity of wild animals and the other based on a model contract for tame animals.
Thermo-optically tunable thin film devices
NASA Astrophysics Data System (ADS)
Domash, Lawrence H.
2003-10-01
We report advances in tunable thin film technology and demonstration of multi-cavity tunable filters. Thin film interference coatings are the most widely used optical technology for telecom filtering, but until recently no tunable versions have been known except for mechanically rotated filters. We describe a new approach to broadly tunable components based on the properties of semiconductor thin films with large thermo-optic coefficients. The technology is based on amorphous silicon deposited by plasma-enhanced chemical vapor deposition (PECVD), a process adapted for telecom applications from its origins in the flat-panel display and solar cell industries. Unlike MEMS devices, tunable thin films can be constructed in sophisticated multi-cavity, multi-layer optical designs.
Evidence-Based Evaluation And Management Of Patients With Pharyngitis In The Emergency Department.
Hildreth, Amy F; Takhar, Sukhjit; Clark, Mark Andrew; Hatten, Benjamin
2015-09-01
Pharyngitis is a common presentation, but it can also be associated with life-threatening processes, including sepsis and airway compromise. Other conditions, such as thyroid disease and cardiac disease, may mimic pharyngitis. The emergency clinician must sort through the broad differential for this complaint using a systematic approach that protects against early closure of the diagnosis. This issue reviews the various international guidelines for pharyngitis and notes controversies in diagnostic and treatment strategies, specifically for management of suspected bacterial, viral, and fungal etiology. A management algorithm is presented, with recommendations based on a review of the best available evidence, taking into account patient comfort and outcomes, the need to reduce bacterial resistance, and costs.
Evaluating the Impact of the U.S. National Toxicology Program: A Case Study on Hexavalent Chromium
Xie, Yun; Holmgren, Stephanie; Andrews, Danica M. K.; Wolfe, Mary S.
2016-01-01
Background: Evaluating the impact of federally funded research with a broad, methodical, and objective approach is important to ensure that public funds advance the mission of federal agencies. Objectives: We aimed to develop a methodical approach that would yield a broad assessment of National Toxicology Program’s (NTP’s) effectiveness across multiple sectors and demonstrate the utility of the approach through a case study. Methods: A conceptual model was developed with defined activities, outputs (products), and outcomes (proximal, intermediate, distal) and applied retrospectively to NTP’s research on hexavalent chromium (CrVI). Proximal outcomes were measured by counting views of and requests for NTP’s products by external stakeholders. Intermediate outcomes were measured by bibliometric analysis. Distal outcomes were assessed through Web and LexisNexis searches for documents related to legislation or regulation changes. Results: The approach identified awareness of NTP’s work on CrVI by external stakeholders (proximal outcome) and citations of NTP’s research in scientific publications, reports, congressional testimonies, and legal and policy documents (intermediate outcome). NTP’s research was key to the nation’s first-ever drinking water standard for CrVI adopted by California in 2014 (distal outcome). By applying this approach to a case study, the utility and limitations of the approach were identified, including challenges to evaluating the outcomes of a research program. Conclusions: This study identified a broad and objective approach for assessing NTP’s effectiveness, including methodological needs for more thorough and efficient impact assessments in the future. Citation: Xie Y, Holmgren S, Andrews DMK, Wolfe MS. 2017. Evaluating the impact of the U.S. National Toxicology Program: a case study on hexavalent chromium. Environ Health Perspect 125:181–188; http://dx.doi.org/10.1289/EHP21 PMID:27483499
Evaluating the Impact of the U.S. National Toxicology Program: A Case Study on Hexavalent Chromium.
Xie, Yun; Holmgren, Stephanie; Andrews, Danica M K; Wolfe, Mary S
2017-02-01
Evaluating the impact of federally funded research with a broad, methodical, and objective approach is important to ensure that public funds advance the mission of federal agencies. We aimed to develop a methodical approach that would yield a broad assessment of National Toxicology Program's (NTP's) effectiveness across multiple sectors and demonstrate the utility of the approach through a case study. A conceptual model was developed with defined activities, outputs (products), and outcomes (proximal, intermediate, distal) and applied retrospectively to NTP's research on hexavalent chromium (CrVI). Proximal outcomes were measured by counting views of and requests for NTP's products by external stakeholders. Intermediate outcomes were measured by bibliometric analysis. Distal outcomes were assessed through Web and LexisNexis searches for documents related to legislation or regulation changes. The approach identified awareness of NTP's work on CrVI by external stakeholders (proximal outcome) and citations of NTP's research in scientific publications, reports, congressional testimonies, and legal and policy documents (intermediate outcome). NTP's research was key to the nation's first-ever drinking water standard for CrVI adopted by California in 2014 (distal outcome). By applying this approach to a case study, the utility and limitations of the approach were identified, including challenges to evaluating the outcomes of a research program. This study identified a broad and objective approach for assessing NTP's effectiveness, including methodological needs for more thorough and efficient impact assessments in the future. Citation: Xie Y, Holmgren S, Andrews DMK, Wolfe MS. 2017. Evaluating the impact of the U.S. National Toxicology Program: a case study on hexavalent chromium. Environ Health Perspect 125:181-188; http://dx.doi.org/10.1289/EHP21.
Reflexive Principlism as an Effective Approach for Developing Ethical Reasoning in Engineering.
Beever, Jonathan; Brightman, Andrew O
2016-02-01
An important goal of teaching ethics to engineering students is to enhance their ability to make well-reasoned ethical decisions in their engineering practice: a goal in line with the stated ethical codes of professional engineering organizations. While engineering educators have explored a wide range of methodologies for teaching ethics, a satisfying model for developing ethical reasoning skills has not been adopted broadly. In this paper we argue that a principlist-based approach to ethical reasoning is uniquely suited to engineering ethics education. Reflexive Principlism is an approach to ethical decision-making that focuses on internalizing a reflective and iterative process of specification, balancing, and justification of four core ethical principles in the context of specific cases. In engineering, that approach provides structure to ethical reasoning while allowing the flexibility for adaptation to varying contexts through specification. Reflexive Principlism integrates well with the prevalent and familiar methodologies of reasoning within the engineering disciplines as well as with the goals of engineering ethics education.
Systems Approach to Arms Control Verification
DOE Office of Scientific and Technical Information (OSTI.GOV)
Allen, K; Neimeyer, I; Listner, C
2015-05-15
Using the decades of experience of developing concepts and technologies for verifying bilateral and multilateral arms control agreements, a broad conceptual systems approach is being developed that takes into account varying levels of information and risk. The IAEA has already demonstrated the applicability of a systems approach by implementing safeguards at the State level, with acquisition path analysis as the key element. In order to test whether such an approach could also be implemented for arms control verification, an exercise was conducted in November 2014 at the JRC ITU Ispra. Based on the scenario of a hypothetical treaty between twomore » model nuclear weapons states aimed at capping their nuclear arsenals at existing levels, the goal of this exercise was to explore how to use acquisition path analysis in an arms control context. Our contribution will present the scenario, objectives and results of this exercise, and attempt to define future workshops aimed at further developing verification measures that will deter or detect treaty violations.« less
Andrews, Ross N; Narayanan, Suresh; Zhang, Fan; Kuzmenko, Ivan; Ilavsky, Jan
2018-02-01
X-ray photon correlation spectroscopy (XPCS), an extension of dynamic light scattering (DLS) in the X-ray regime, detects temporal intensity fluctuations of coherent speckles and provides scattering vector-dependent sample dynamics at length scales smaller than DLS. The penetrating power of X-rays enables probing dynamics in a broad array of materials with XPCS, including polymers, glasses and metal alloys, where attempts to describe the dynamics with a simple exponential fit usually fails. In these cases, the prevailing XPCS data analysis approach employs stretched or compressed exponential decay functions (Kohlrausch functions), which implicitly assume homogeneous dynamics. In this paper, we propose an alternative analysis scheme based upon inverse Laplace or Gaussian transformation for elucidating heterogeneous distributions of dynamic time scales in XPCS, an approach analogous to the CONTIN algorithm widely accepted in the analysis of DLS from polydisperse and multimodal systems. Using XPCS data measured from colloidal gels, we demonstrate the inverse transform approach reveals hidden multimodal dynamics in materials, unleashing the full potential of XPCS.
Andrews, Ross N.; Narayanan, Suresh; Zhang, Fan; Kuzmenko, Ivan; Ilavsky, Jan
2018-01-01
X-ray photon correlation spectroscopy (XPCS), an extension of dynamic light scattering (DLS) in the X-ray regime, detects temporal intensity fluctuations of coherent speckles and provides scattering vector-dependent sample dynamics at length scales smaller than DLS. The penetrating power of X-rays enables probing dynamics in a broad array of materials with XPCS, including polymers, glasses and metal alloys, where attempts to describe the dynamics with a simple exponential fit usually fails. In these cases, the prevailing XPCS data analysis approach employs stretched or compressed exponential decay functions (Kohlrausch functions), which implicitly assume homogeneous dynamics. In this paper, we propose an alternative analysis scheme based upon inverse Laplace or Gaussian transformation for elucidating heterogeneous distributions of dynamic time scales in XPCS, an approach analogous to the CONTIN algorithm widely accepted in the analysis of DLS from polydisperse and multimodal systems. Using XPCS data measured from colloidal gels, we demonstrate the inverse transform approach reveals hidden multimodal dynamics in materials, unleashing the full potential of XPCS. PMID:29875506
NASA Technical Reports Server (NTRS)
Moeller, Robert C.; Borden, Chester; Spilker, Thomas; Smythe, William; Lock, Robert
2011-01-01
The JPL Rapid Mission Architecture (RMA) capability is a novel collaborative team-based approach to generate new mission architectures, explore broad trade space options, and conduct architecture-level analyses. RMA studies address feasibility and identify best candidates to proceed to further detailed design studies. Development of RMA first began at JPL in 2007 and has evolved to address the need for rapid, effective early mission architectural development and trade space exploration as a precursor to traditional point design evaluations. The RMA approach integrates a small team of architecture-level experts (typically 6-10 people) to generate and explore a wide-ranging trade space of mission architectures driven by the mission science (or technology) objectives. Group brainstorming and trade space analyses are conducted at a higher level of assessment across multiple mission architectures and systems to enable rapid assessment of a set of diverse, innovative concepts. This paper describes the overall JPL RMA team, process, and high-level approach. Some illustrative results from previous JPL RMA studies are discussed.
Developing a Measure of Value in Health Care.
Ken Lee, K H; Matthew Austin, J; Pronovost, Peter J
2016-06-01
There is broad support to pay for value, rather than volume, for health care in the United States. Despite the support, practical approaches for measuring value remain elusive. Value is commonly defined as quality divided by costs, where quality reflects patient outcomes and costs are the total costs for providing care, whether these be costs related to an episode, a diagnosis, or per capita. Academicians have proposed a conceptual approach to measure value, in which we measure outcomes important to patients and costs using time-driven activity-based costing. This approach is conceptually sound, but has significant practical challenges. In our commentary, we describe how health care can use existing quality measures and cost accounting data to measure value. Although not perfect, we believe this approach is practical, valid, and scalable and can establish the foundation for future work in this area. Copyright © 2016 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
What Synthesis Methodology Should I Use? A Review and Analysis of Approaches to Research Synthesis
Schick-Makaroff, Kara; MacDonald, Marjorie; Plummer, Marilyn; Burgess, Judy; Neander, Wendy
2016-01-01
Background When we began this process, we were doctoral students and a faculty member in a research methods course. As students, we were facing a review of the literature for our dissertations. We encountered several different ways of conducting a review but were unable to locate any resources that synthesized all of the various synthesis methodologies. Our purpose is to present a comprehensive overview and assessment of the main approaches to research synthesis. We use ‘research synthesis’ as a broad overarching term to describe various approaches to combining, integrating, and synthesizing research findings. Methods We conducted an integrative review of the literature to explore the historical, contextual, and evolving nature of research synthesis. We searched five databases, reviewed websites of key organizations, hand-searched several journals, and examined relevant texts from the reference lists of the documents we had already obtained. Results We identified four broad categories of research synthesis methodology including conventional, quantitative, qualitative, and emerging syntheses. Each of the broad categories was compared to the others on the following: key characteristics, purpose, method, product, context, underlying assumptions, unit of analysis, strengths and limitations, and when to use each approach. Conclusions The current state of research synthesis reflects significant advancements in emerging synthesis studies that integrate diverse data types and sources. New approaches to research synthesis provide a much broader range of review alternatives available to health and social science students and researchers. PMID:29546155
75 FR 30842 - Statutorily Mandated Single Source Award Program Name: National Indian Health Board
Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-02
... health care advocacy to IHS and HHS based on Tribal input through a broad based consumer network. The.... To assure that health care advocacy is based on Tribal input through a broad-based consumer network... maintenance. B. Organizational Capabilities and Qualifications (30 Points) (1) Describe the organizational...
Integration of Continuous-Time Dynamics in a Spiking Neural Network Simulator.
Hahne, Jan; Dahmen, David; Schuecker, Jannis; Frommer, Andreas; Bolten, Matthias; Helias, Moritz; Diesmann, Markus
2017-01-01
Contemporary modeling approaches to the dynamics of neural networks include two important classes of models: biologically grounded spiking neuron models and functionally inspired rate-based units. We present a unified simulation framework that supports the combination of the two for multi-scale modeling, enables the quantitative validation of mean-field approaches by spiking network simulations, and provides an increase in reliability by usage of the same simulation code and the same network model specifications for both model classes. While most spiking simulations rely on the communication of discrete events, rate models require time-continuous interactions between neurons. Exploiting the conceptual similarity to the inclusion of gap junctions in spiking network simulations, we arrive at a reference implementation of instantaneous and delayed interactions between rate-based models in a spiking network simulator. The separation of rate dynamics from the general connection and communication infrastructure ensures flexibility of the framework. In addition to the standard implementation we present an iterative approach based on waveform-relaxation techniques to reduce communication and increase performance for large-scale simulations of rate-based models with instantaneous interactions. Finally we demonstrate the broad applicability of the framework by considering various examples from the literature, ranging from random networks to neural-field models. The study provides the prerequisite for interactions between rate-based and spiking models in a joint simulation.
Integration of Continuous-Time Dynamics in a Spiking Neural Network Simulator
Hahne, Jan; Dahmen, David; Schuecker, Jannis; Frommer, Andreas; Bolten, Matthias; Helias, Moritz; Diesmann, Markus
2017-01-01
Contemporary modeling approaches to the dynamics of neural networks include two important classes of models: biologically grounded spiking neuron models and functionally inspired rate-based units. We present a unified simulation framework that supports the combination of the two for multi-scale modeling, enables the quantitative validation of mean-field approaches by spiking network simulations, and provides an increase in reliability by usage of the same simulation code and the same network model specifications for both model classes. While most spiking simulations rely on the communication of discrete events, rate models require time-continuous interactions between neurons. Exploiting the conceptual similarity to the inclusion of gap junctions in spiking network simulations, we arrive at a reference implementation of instantaneous and delayed interactions between rate-based models in a spiking network simulator. The separation of rate dynamics from the general connection and communication infrastructure ensures flexibility of the framework. In addition to the standard implementation we present an iterative approach based on waveform-relaxation techniques to reduce communication and increase performance for large-scale simulations of rate-based models with instantaneous interactions. Finally we demonstrate the broad applicability of the framework by considering various examples from the literature, ranging from random networks to neural-field models. The study provides the prerequisite for interactions between rate-based and spiking models in a joint simulation. PMID:28596730
The Hard Way towards an Antibody-Based HIV-1 Env Vaccine: Lessons from Other Viruses
Ringel, Oliver; Vieillard, Vincent; Debré, Patrice; Eichler, Jutta; Büning, Hildegard
2018-01-01
Although effective antibody-based vaccines have been developed against multiple viruses, such approaches have so far failed for the human immunodeficiency virus type 1 (HIV-1). Despite the success of anti-retroviral therapy (ART) that has turned HIV-1 infection into a chronic disease and has reduced the number of new infections worldwide, a vaccine against HIV-1 is still urgently needed. We discuss here the major reasons for the failure of “classical” vaccine approaches, which are mostly due to the biological properties of the virus itself. HIV-1 has developed multiple mechanisms of immune escape, which also account for vaccine failure. So far, no vaccine candidate has been able to induce broadly neutralizing antibodies (bnAbs) against primary patient viruses from different clades. However, such antibodies were identified in a subset of patients during chronic infection and were shown to protect from infection in animal models and to reduce viremia in first clinical trials. Their detailed characterization has guided structure-based reverse vaccinology approaches to design better HIV-1 envelope (Env) immunogens. Furthermore, conserved Env epitopes have been identified, which are promising candidates in view of clinical applications. Together with new vector-based technologies, considerable progress has been achieved in recent years towards the development of an effective antibody-based HIV-1 vaccine. PMID:29662026
Rational engineering of nanoporous anodic alumina optical bandpass filters
NASA Astrophysics Data System (ADS)
Santos, Abel; Pereira, Taj; Law, Cheryl Suwen; Losic, Dusan
2016-08-01
Herein, we present a rationally designed advanced nanofabrication approach aiming at producing a new type of optical bandpass filters based on nanoporous anodic alumina photonic crystals. The photonic stop band of nanoporous anodic alumina (NAA) is engineered in depth by means of a pseudo-stepwise pulse anodisation (PSPA) approach consisting of pseudo-stepwise asymmetric current density pulses. This nanofabrication method makes it possible to tune the transmission bands of NAA at specific wavelengths and bandwidths, which can be broadly modified across the UV-visible-NIR spectrum through the anodisation period (i.e. time between consecutive pulses). First, we establish the effect of the anodisation period as a means of tuning the position and width of the transmission bands of NAA across the UV-visible-NIR spectrum. To this end, a set of nanoporous anodic alumina bandpass filters (NAA-BPFs) are produced with different anodisation periods, ranging from 500 to 1200 s, and their optical properties (i.e. characteristic transmission bands and interferometric colours) are systematically assessed. Then, we demonstrate that the rational combination of stacked NAA-BPFs consisting of layers of NAA produced with different PSPA periods can be readily used to create a set of unique and highly selective optical bandpass filters with characteristic transmission bands, the position, width and number of which can be precisely engineered by this rational anodisation approach. Finally, as a proof-of-concept, we demonstrate that the superposition of stacked NAA-BPFs produced with slight modifications of the anodisation period enables the fabrication of NAA-BPFs with unprecedented broad transmission bands across the UV-visible-NIR spectrum. The results obtained from our study constitute the first comprehensive rationale towards advanced NAA-BPFs with fully controllable photonic properties. These photonic crystal structures could become a promising alternative to traditional optical bandpass filters based on glass and plastic.Herein, we present a rationally designed advanced nanofabrication approach aiming at producing a new type of optical bandpass filters based on nanoporous anodic alumina photonic crystals. The photonic stop band of nanoporous anodic alumina (NAA) is engineered in depth by means of a pseudo-stepwise pulse anodisation (PSPA) approach consisting of pseudo-stepwise asymmetric current density pulses. This nanofabrication method makes it possible to tune the transmission bands of NAA at specific wavelengths and bandwidths, which can be broadly modified across the UV-visible-NIR spectrum through the anodisation period (i.e. time between consecutive pulses). First, we establish the effect of the anodisation period as a means of tuning the position and width of the transmission bands of NAA across the UV-visible-NIR spectrum. To this end, a set of nanoporous anodic alumina bandpass filters (NAA-BPFs) are produced with different anodisation periods, ranging from 500 to 1200 s, and their optical properties (i.e. characteristic transmission bands and interferometric colours) are systematically assessed. Then, we demonstrate that the rational combination of stacked NAA-BPFs consisting of layers of NAA produced with different PSPA periods can be readily used to create a set of unique and highly selective optical bandpass filters with characteristic transmission bands, the position, width and number of which can be precisely engineered by this rational anodisation approach. Finally, as a proof-of-concept, we demonstrate that the superposition of stacked NAA-BPFs produced with slight modifications of the anodisation period enables the fabrication of NAA-BPFs with unprecedented broad transmission bands across the UV-visible-NIR spectrum. The results obtained from our study constitute the first comprehensive rationale towards advanced NAA-BPFs with fully controllable photonic properties. These photonic crystal structures could become a promising alternative to traditional optical bandpass filters based on glass and plastic. Electronic supplementary information (ESI) available: An example demonstrating the effect of pore widening on the position and width of the transmission band of a NAA-BPF and a comprehensive table summarising the position and FWHM of the different bands of the NAA-BPFs produced in this study. See DOI: 10.1039/c6nr03490j
Accurate force field for molybdenum by machine learning large materials data
NASA Astrophysics Data System (ADS)
Chen, Chi; Deng, Zhi; Tran, Richard; Tang, Hanmei; Chu, Iek-Heng; Ong, Shyue Ping
2017-09-01
In this work, we present a highly accurate spectral neighbor analysis potential (SNAP) model for molybdenum (Mo) developed through the rigorous application of machine learning techniques on large materials data sets. Despite Mo's importance as a structural metal, existing force fields for Mo based on the embedded atom and modified embedded atom methods do not provide satisfactory accuracy on many properties. We will show that by fitting to the energies, forces, and stress tensors of a large density functional theory (DFT)-computed dataset on a diverse set of Mo structures, a Mo SNAP model can be developed that achieves close to DFT accuracy in the prediction of a broad range of properties, including elastic constants, melting point, phonon spectra, surface energies, grain boundary energies, etc. We will outline a systematic model development process, which includes a rigorous approach to structural selection based on principal component analysis, as well as a differential evolution algorithm for optimizing the hyperparameters in the model fitting so that both the model error and the property prediction error can be simultaneously lowered. We expect that this newly developed Mo SNAP model will find broad applications in large and long-time scale simulations.
Breuckmann, Frank; Gambichler, Thilo; Altmeyer, Peter; Kreuter, Alexander
2004-01-01
Background Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. Methods Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. Results Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. Conclusions Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications. PMID:15380024
Exploring Metaphors for Making Data Broadly Available.
NASA Astrophysics Data System (ADS)
Parsons, M.; Fox, P.
2012-04-01
As international attention to scientific data continues to grow in today's born digital and Internet age, we take the opportunity to re-visit long-standing approaches to managing data and to critically examine some proposed new capabilities. In this presentation we build on our preliminary exploration of multiple metaphors co-existing in support of a healthy data ecosystem, and discuss what we see as key data ecosystem attributes embedded in modern approaches to data managment across the broad spectrum of geoscientific data and geoscientists. We conclude with a set of suggestions and actions to engage the world wide data and information science community to advance such a discussion.
Wang, Yanying; Liu, Yaqin; Ding, Fang; Zhu, Xiaoyan; Yang, Li; Zou, Ping; Rao, Hanbing; Zhao, Qingbiao; Wang, Xianxiang
2018-06-07
In this study, we developed a simple colorimetric approach to detect glutathione (GSH). The proposed approach is based on the ability of CuS-PDA-Au composite material to catalytically oxidize 3,3',5,5'-tetramethylbenzidine (TMB) to ox-TMB to induce a blue color with an absorption peak centered at 652 nm. However, the introduction of GSH can result in a decrease in oxidized TMB; similarly, it can combine with Au nanoparticles (Au NPs) on the surface of CuS-PDA-Au composite material. Both approaches can result in a fading blue color and a reduction of the absorbance at 652 nm. Based on this above, we proposed a technique to detect GSH quantitatively and qualitatively through UV-Vis spectroscopy and naked eye, respectively. This approach demonstrates a low detection limit of 0.42 μM with a broad detection range of 5 × 10 -7 -1 × 10 -4 M with the assistance of UV-Vis spectroscopy. More importantly, this approach is convenient and rapid. This method was successfully applied to GSH detection in human serum and cell lines. Graphical abstract A colorimetric approach has been developed by exploiting the peroxidase-like activity of CuS-polydopamine-Au composite for sensitive glutathione detection.
Severity assessment scores to guide empirical use of antibiotics in community acquired pneumonia.
Singanayagam, Aran; Chalmers, James D
2013-10-01
Severity assessment scores were first developed to predict the 30 day mortality in community acquired pneumonia; however, several guidelines have extended their use to guide empirical antibiotic prescription decisions. This approach has theoretical advantages because a decrease in broad-spectrum antibiotic treatment in low-risk patients might reduce antibiotic-related side-effects, and to give broad-spectrum therapy to patients at higher risk of death is intuitive. However, evidence in support of this approach is not clear. In particular, the British Thoracic Society guidelines suggest withholding a macrolide from patients with low CURB 65 scores, despite evidence that these patients have a higher frequency of atypical pathogens than do those with a higher severity of pneumonia. Severity scores do not perform well in some groups and might overestimate disease severity in elderly people, leading to inappropriate broad-spectrum treatment to those at high risk of complications such as Clostridium difficile infection. In this Review, we discuss the evidence for antibiotic prescribing guided by severity score and suggest that more evidence of effect and implementation is needed before this approach can be universally adopted. Copyright © 2013 Elsevier Ltd. All rights reserved.
Subjective Age Bias: A Motivational and Information Processing Approach
ERIC Educational Resources Information Center
Teuscher, Ursina
2009-01-01
There is broad empirical evidence, but still a lack of theoretical explanations, for the phenomenon that most older people feel considerably younger than their real age. In this article, a measurement model of subjective age was assessed, and two independent theoretical approaches are proposed: (1) a motivational approach assuming that the age…
Multifaceted Approach to Designing an Online Masters Program.
ERIC Educational Resources Information Center
McNeil, Sara G.; Chernish, William N.; DeFranco, Agnes L.
At the Conrad N. Hilton College of Hotel and Restaurant Management at the University of Houston (Texas), the faculty and administrators made a conscious effort to take a broad, extensive approach to designing and implementing a fully online masters program. This approach was entered in a comprehensive needs assessment model and sought input from…
An African-Centred Approach to Land Education
ERIC Educational Resources Information Center
Engel-Di Mauro, Salvatore; Carroll, Karanja Keita
2014-01-01
Approaches to environmental education which are engaging with place and critical pedagogy have not yet broadly engaged with the African world and insights from Africana Studies and Geography. An African-centred approach facilitates people's reconnection to places and ecosystems in ways that do not reduce places to objects of conquest and…
Vibration suppression of a piezo-equipped cylindrical shell in a broad-band frequency domain
NASA Astrophysics Data System (ADS)
Loghmani, Ali; Danesh, Mohammad; Kwak, Moon K.; Keshmiri, Mehdi
2017-12-01
This paper focuses on the dynamic modeling of a cylindrical shell equipped with piezoceramic sensors and actuators, as well as the design of a broad band multi-input and multi-output linear quadratic Gaussian controller for the suppression of vibrations. The optimal locations of actuators are derived by Genetic Algorithm (GA) to effectively control the specific structural modes of the cylinder. The dynamic model is derived based on the Sanders shell theory and the energy approach for both the cylinder and the piezoelectric transducers, all of which reflect the piezoelectric effect. The natural vibration characteristics of the cylindrical shell are investigated both theoretically and experimentally. The theoretical predictions are in good agreement with the experimental results. Then, the broad band multi-input and multi-output linear quadratic Gaussian controller was designed and applied to the test article. An active vibration control experiment is carried out on the cylindrical shell and the digital control system is used to implement the proposed control algorithm. The experimental results show that vibrations of the cylindrical shell can be suppressed by the piezoceramic sensors and actuators along with the proposed controller. The optimal location of the actuators makes the proposed control system more efficient than other configurations.
Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface
DOE Office of Scientific and Technical Information (OSTI.GOV)
Huang, Jinghe; Kang, Byong H.; Pancera, Marie
The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC 50) <50 μg ml -1. The median IC 50 of neutralized viruses was 0.033 μg ml -1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and amore » reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.« less
Towards substrate engineering of graphene-silicon Schottky diode photodetectors.
Selvi, Hakan; Unsuree, Nawapong; Whittaker, Eric; Halsall, Matthew P; Hill, Ernie W; Thomas, Andrew; Parkinson, Patrick; Echtermeyer, Tim J
2018-02-15
Graphene-silicon Schottky diode photodetectors possess beneficial properties such as high responsivities and detectivities, broad spectral wavelength operation and high operating speeds. Various routes and architectures have been employed in the past to fabricate devices. Devices are commonly based on the removal of the silicon-oxide layer on the surface of silicon by wet-etching before deposition of graphene on top of silicon to form the graphene-silicon Schottky junction. In this work, we systematically investigate the influence of the interfacial oxide layer, the fabrication technique employed and the silicon substrate on the light detection capabilities of graphene-silicon Schottky diode photodetectors. The properties of devices are investigated over a broad wavelength range from near-UV to short-/mid-infrared radiation, radiation intensities covering over five orders of magnitude as well as the suitability of devices for high speed operation. Results show that the interfacial layer, depending on the required application, is in fact beneficial to enhance the photodetection properties of such devices. Further, we demonstrate the influence of the silicon substrate on the spectral response and operating speed. Fabricated devices operate over a broad spectral wavelength range from the near-UV to the short-/mid-infrared (thermal) wavelength regime, exhibit high photovoltage responses approaching 10 6 V W -1 and short rise- and fall-times of tens of nanoseconds.
An optimized web-based approach for collaborative stereoscopic medical visualization
Kaspar, Mathias; Parsad, Nigel M; Silverstein, Jonathan C
2013-01-01
Objective Medical visualization tools have traditionally been constrained to tethered imaging workstations or proprietary client viewers, typically part of hospital radiology systems. To improve accessibility to real-time, remote, interactive, stereoscopic visualization and to enable collaboration among multiple viewing locations, we developed an open source approach requiring only a standard web browser with no added client-side software. Materials and Methods Our collaborative, web-based, stereoscopic, visualization system, CoWebViz, has been used successfully for the past 2 years at the University of Chicago to teach immersive virtual anatomy classes. It is a server application that streams server-side visualization applications to client front-ends, comprised solely of a standard web browser with no added software. Results We describe optimization considerations, usability, and performance results, which make CoWebViz practical for broad clinical use. We clarify technical advances including: enhanced threaded architecture, optimized visualization distribution algorithms, a wide range of supported stereoscopic presentation technologies, and the salient theoretical and empirical network parameters that affect our web-based visualization approach. Discussion The implementations demonstrate usability and performance benefits of a simple web-based approach for complex clinical visualization scenarios. Using this approach overcomes technical challenges that require third-party web browser plug-ins, resulting in the most lightweight client. Conclusions Compared to special software and hardware deployments, unmodified web browsers enhance remote user accessibility to interactive medical visualization. Whereas local hardware and software deployments may provide better interactivity than remote applications, our implementation demonstrates that a simplified, stable, client approach using standard web browsers is sufficient for high quality three-dimensional, stereoscopic, collaborative and interactive visualization. PMID:23048008
Kerrigan, Deanna; Kennedy, Caitlin E; Morgan-Thomas, Ruth; Reza-Paul, Sushena; Mwangi, Peninah; Win, Kay Thi; McFall, Allison; Fonner, Virginia A; Butler, Jennifer
2015-01-10
A community empowerment-based response to HIV is a process by which sex workers take collective ownership of programmes to achieve the most effective HIV outcomes and address social and structural barriers to their overall health and human rights. Community empowerment has increasingly gained recognition as a key approach for addressing HIV in sex workers, with its focus on addressing the broad context within which the heightened risk for infection takes places in these individuals. However, large-scale implementation of community empowerment-based approaches has been scarce. We undertook a comprehensive review of community empowerment approaches for addressing HIV in sex workers. Within this effort, we did a systematic review and meta-analysis of the effectiveness of community empowerment in sex workers in low-income and middle-income countries. We found that community empowerment-based approaches to addressing HIV among sex workers were significantly associated with reductions in HIV and other sexually transmitted infections, and with increases in consistent condom use with all clients. Despite the promise of a community-empowerment approach, we identified formidable structural barriers to implementation and scale-up at various levels. These barriers include regressive international discourses and funding constraints; national laws criminalising sex work; and intersecting social stigmas, discrimination, and violence. The evidence base for community empowerment in sex workers needs to be strengthened and diversified, including its role in aiding access to, and uptake of, combination interventions for HIV prevention. Furthermore, social and political change are needed regarding the recognition of sex work as work, both globally and locally, to encourage increased support for community empowerment responses to HIV. Copyright © 2015 Elsevier Ltd. All rights reserved.
NASA Astrophysics Data System (ADS)
Myers, B.; Beard, T. D.; Weiskopf, S. R.; Jackson, S. T.; Tittensor, D.; Harfoot, M.; Senay, G. B.; Casey, K.; Lenton, T. M.; Leidner, A. K.; Ruane, A. C.; Ferrier, S.; Serbin, S.; Matsuda, H.; Shiklomanov, A. N.; Rosa, I.
2017-12-01
Biodiversity and ecosystems services underpin political targets for the conservation of biodiversity; however, previous incarnations of these biodiversity-related targets have not relied on integrated model based projections of possible outcomes based on climate and land use change. Although a few global biodiversity models are available, most biodiversity models lie along a continuum of geography and components of biodiversity. Model-based projections of the future of global biodiversity are critical to support policymakers in the development of informed global conservation targets, but the scientific community lacks a clear strategy for integrating diverse data streams in developing, and evaluating the performance of, such biodiversity models. Therefore, in this paper, we propose a framework for ongoing testing and refinement of model-based projections of biodiversity trends and change, by linking a broad variety of biodiversity models with data streams generated by advances in remote sensing, coupled with new and emerging in-situ observation technologies to inform development of essential biodiversity variables, future global biodiversity targets, and indicators. Our two main objectives are to (1) develop a framework for model testing and refining projections of a broad range of biodiversity models, focusing on global models, through the integration of diverse data streams and (2) identify the realistic outputs that can be developed and determine coupled approaches using remote sensing and new and emerging in-situ observations (e.g., metagenomics) to better inform the next generation of global biodiversity targets.
Cederholm, Tommy; Jensen, Gordon L
2017-02-01
During the ESPEN Congress in Copenhagen, Denmark (September 2016) representatives of the 4 largest global PEN-societies from Europe (ESPEN), USA (ASPEN), Asia (PENSA) and Latin America (FELANPE), and from national PEN-societies around the world met to continue the conversation on how to diagnose malnutrition that started during the Clinical Nutrition Week, Austin, USA (February 2016). Current thinking on diagnostic approaches was shared; ESPEN suggested a grading approach that could encompass various types of signs, symptoms and etiologies to support diagnosis. ASPEN emphasized where the parties agree; i.e. that the three major published approaches (ESPEN, ASPEN/AND and Subjective Global Assessment (SGA)) all propose weight loss as a key indicator for malnutrition. FELANPE suggested that the anticipated consensus approach needs to prioritize a diagnostic methodology that is available for everybody since resources differ globally. PENSA highlighted that BMI varies by ethnicity/race, and that sarcopenia/muscle mass evaluation is important for the diagnosis of malnutrition. A Core Working Committee of the Global Leadership Initiative on Malnutrition (GLIM) has been established (comprised of two representatives each from the 4 largest PEN-societies) that will lead consensus development in collaboration with a larger Working Group with broad global representation, using e-mail, telephone conferences, and face-to-face meetings during the up-coming ASPEN and ESPEN Congresses. Transparency and external input will be sought. Objectives include: 1. Consensus development around evidence-based criteria for broad application. 2. Promotion of global dissemination of the consensus criteria. 3. Seeking adoption by the World Health Organization (WHO) and the International Classification of Diseases (ICD). Copyright © 2017 American Society for Parenteral and Enteral Nutrition, Elsevier Ltd, European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd.. All rights reserved.
To Create a Consensus on Malnutrition Diagnostic Criteria.
Cederholm, Tommy; Jensen, Gordon L
2017-03-01
During the European Society for Clinical Nutrition and Metabolism (ESPEN) Congress in Copenhagen, Denmark (September 2016), representatives of the 4 largest global parenteral and enteral nutrition (PEN) societies from Europe (ESPEN), the United States (American Society for Parenteral and Enteral Nutrition [ASPEN]), Asia (Parenteral and Enteral Nutrition Society of Asia [PENSA]), and Latin America (Latin American Federation of Parenteral and Enteral Nutrition [FELANPE]) and from national PEN societies around the world met to continue the conversation on how to diagnose malnutrition that started during the Clinical Nutrition Week, Austin, Texas (February 2016). Current thinking on diagnostic approaches was shared; ESPEN suggested a grading approach that could encompass various types of signs, symptoms, and etiologies to support diagnosis. ASPEN emphasized where the parties agree; that is, that the 3 major published approaches (ESPEN, ASPEN-Academy of Nutrition and Dietetics, and Subjective Global Assessment [SGA]) all propose weight loss as a key indicator for malnutrition. FELANPE suggested that the anticipated consensus approach needs to prioritize a diagnostic method that is available for everybody since resources differ globally. PENSA highlighted that body mass index varies by ethnicity/race and that sarcopenia/muscle mass evaluation is important for the diagnosis of malnutrition. A Core Working Committee of the Global Leadership Initiative on Malnutrition has been established (comprising 2 representatives each from the 4 largest PEN societies) that will lead consensus development in collaboration with a larger working group with broad global representation, using e-mail, telephone conferences, and face-to-face meetings during the upcoming ASPEN and ESPEN congresses. Transparency and external input will be sought. Objectives include (1) consensus development around evidence-based criteria for broad application, (2) promotion of global dissemination of the consensus criteria, and (3) seeking adoption by the World Health Organization and the International Classification of Diseases.
O'Donnell, Sean T; Caldwell, Michael D; Barlaz, Morton A; Morris, Jeremy W F
2018-05-01
Municipal solid waste (MSW) landfills in the USA are regulated under Subtitle D of the Resource Conservation and Recovery Act (RCRA), which includes the requirement to protect human health and the environment (HHE) during the post-closure care (PCC) period. Several approaches have been published for assessment of potential threats to HHE. These approaches can be broadly divided into organic stabilization, which establishes an inert waste mass as the ultimate objective, and functional stability, which considers long-term emissions in the context of minimizing threats to HHE in the absence of active controls. The objective of this research was to conduct a case study evaluation of a closed MSW landfill using long-term data on landfill gas (LFG) production, leachate quality, site geology, and solids decomposition. Evaluations based on both functional and organic stability criteria were compared. The results showed that longer periods of LFG and leachate management would be required using organic stability criteria relative to an approach based on functional stability. These findings highlight the somewhat arbitrary and overly stringent nature of assigning universal stability criteria without due consideration of the landfill's hydrogeologic setting and potential environmental receptors. This supports previous studies that advocated for transition to a passive or inactive control stage based on a performance-based functional stability framework as a defensible mechanism for optimizing and ending regulatory PCC. Copyright © 2018 Elsevier Ltd. All rights reserved.
Muntinga, M E; Krajenbrink, V Q E; Peerdeman, S M; Croiset, G; Verdonk, P
2016-08-01
Recent years have seen a rise in the efforts to implement diversity topics into medical education, using either a 'narrow' or a 'broad' definition of culture. These developments urge that outcomes of such efforts are systematically evaluated by mapping the curriculum for diversity-responsive content. This study was aimed at using an intersectionality-based approach to define diversity-related learning objectives and to evaluate how biomedical and sociocultural aspects of diversity were integrated into a medical curriculum in the Netherlands. We took a three-phase mixed methods approach. In phase one and two, we defined essential learning objectives based on qualitative interviews with school stakeholders and diversity literature. In phase three, we screened the written curriculum for diversity content (culture, sex/gender and class) and related the results to learning objectives defined in phase two. We identified learning objectives in three areas of education (medical knowledge and skills, patient-physician communication, and reflexivity). Most diversity content pertained to biomedical knowledge and skills. Limited attention was paid to sociocultural issues as determinants of health and healthcare use. Intersections of culture, sex/gender and class remained mostly unaddressed. The curriculum's diversity-responsiveness could be improved by an operationalization of diversity that goes beyond biomedical traits of assumed homogeneous social groups. Future efforts to take an intersectionality-based approach to curriculum evaluations should include categories of difference other than culture, sex/gender and class as separate, equally important patient identities or groups.
Psychotherapy Outcome Research: Issues and Questions.
Shean, Glenn
2016-03-01
Emphasis on identifying evidence-based therapies (EBTs) has increased markedly. Lists of EBTs are the rationale for recommendations for how psychotherapy provider training programs should be evaluated, professional competence assessed, and licensure and reimbursement policies structured. There are however methodological concerns that limit the external validity of EBTs. Among the most salient is the circularity inherent in randomized control trials (RCTs) of psychotherapy that constrains the manner in which the psychological problems are defined, psychotherapy can be practiced, and change evaluated. RCT studies favor therapies that focus of specific symptoms and can be described in a manual, administered reliably across patients, completed in relatively few sessions, and involve short-term evaluations of outcome. The epistemological assumptions of a natural science approach to psychotherapy research limit how studies are conducted and assessed in ways that that advantage symptom-focused approaches and disadvantage those approaches that seek to bring broad recovery-based changes. Research methods that are not limited to RCTs and include methodology to minimize the effects of "therapist allegiance" are necessary for valid evaluations of therapeutic approaches that seek to facilitate changes that are broader than symptom reduction. Recent proposals to adopt policies that dictate training, credentialing, and reimbursement based on lists of EBTs unduly limit how psychotherapy can be conceptualized and practiced, and are not in the best interests of the profession or of individuals seeking psychotherapy services.
How Can We Improve School Discipline?
ERIC Educational Resources Information Center
Osher, David; Bear, George G.; Sprague, Jeffrey R.; Doyle, Walter
2010-01-01
School discipline addresses schoolwide, classroom, and individual student needs through broad prevention, targeted intervention, and development of self-discipline. Schools often respond to disruptive students with exclusionary and punitive approaches that have limited value. This article surveys three approaches to improving school discipline…
NASA Astrophysics Data System (ADS)
Bremer, Leah L.; Delevaux, Jade M. S.; Leary, James J. K.; J. Cox, Linda; Oleson, Kirsten L. L.
2015-04-01
Incorporating ecosystem services into management decisions is a promising means to link conservation and human well-being. Nonetheless, planning and management in Hawai`i, a state with highly valued natural capital, has yet to broadly utilize an ecosystem service approach. We conducted a stakeholder assessment, based on semi-structured interviews, with terrestrial ( n = 26) and marine ( n = 27) natural resource managers across the State of Hawai`i to understand the current use of ecosystem services (ES) knowledge and decision support tools and whether, how, and under what contexts, further development would potentially be useful. We found that ES knowledge and tools customized to Hawai`i could be useful for communication and outreach, justifying management decisions, and spatial planning. Greater incorporation of this approach is clearly desired and has a strong potential to contribute to more sustainable decision making and planning in Hawai`i and other oceanic island systems. However, the unique biophysical, socio-economic, and cultural context of Hawai`i, and other island systems, will require substantial adaptation of existing ES tools. Based on our findings, we identified four key opportunities for the use of ES knowledge and tools in Hawai`i: (1) linking native forest protection to watershed health; (2) supporting sustainable agriculture; (3) facilitating ridge-to-reef management; and (4) supporting statewide terrestrial and marine spatial planning. Given the interest expressed by natural resource managers, we envision broad adoption of ES knowledge and decision support tools if knowledge and tools are tailored to the Hawaiian context and coupled with adequate outreach and training.
Exposing the Science in Citizen Science: Fitness to Purpose and Intentional Design.
Parrish, Julia K; Burgess, Hillary; Weltzin, Jake F; Fortson, Lucy; Wiggins, Andrea; Simmons, Brooke
2018-05-21
Citizen science is a growing phenomenon. With millions of people involved and billions of in-kind dollars contributed annually, this broad extent, fine grain approach to data collection should be garnering enthusiastic support in the mainstream science and higher education communities. However, many academic researchers demonstrate distinct biases against the use of citizen science as a source of rigorous information. To engage the public in scientific research, and the research community in the practice of citizen science, a mutual understanding is needed of accepted quality standards in science, and the corresponding specifics of project design and implementation when working with a broad public base. We define a science-based typology focused on the degree to which projects deliver the type(s) and quality of data/work needed to produce valid scientific outcomes directly useful in science and natural resource management. Where project intent includes direct contribution to science and the public is actively involved either virtually or hands-on, we examine the measures of quality assurance (methods to increase data quality during the design and implementation phases of a project) and quality control (post hoc methods to increase the quality of scientific outcomes). We suggest that high quality science can be produced with massive, largely one-off, participation if data collection is simple and quality control includes algorithm voting, statistical pruning and/or computational modeling. Small to mid-scale projects engaging participants in repeated, often complex, sampling can advance quality through expert-led training and well-designed materials, and through independent verification. Both approaches - simplification at scale and complexity with care - generate more robust science outcomes.
Bremer, Leah L; Delevaux, Jade M S; Leary, James J K; J Cox, Linda; Oleson, Kirsten L L
2015-04-01
Incorporating ecosystem services into management decisions is a promising means to link conservation and human well-being. Nonetheless, planning and management in Hawai'i, a state with highly valued natural capital, has yet to broadly utilize an ecosystem service approach. We conducted a stakeholder assessment, based on semi-structured interviews, with terrestrial (n = 26) and marine (n = 27) natural resource managers across the State of Hawai'i to understand the current use of ecosystem services (ES) knowledge and decision support tools and whether, how, and under what contexts, further development would potentially be useful. We found that ES knowledge and tools customized to Hawai'i could be useful for communication and outreach, justifying management decisions, and spatial planning. Greater incorporation of this approach is clearly desired and has a strong potential to contribute to more sustainable decision making and planning in Hawai'i and other oceanic island systems. However, the unique biophysical, socio-economic, and cultural context of Hawai'i, and other island systems, will require substantial adaptation of existing ES tools. Based on our findings, we identified four key opportunities for the use of ES knowledge and tools in Hawai'i: (1) linking native forest protection to watershed health; (2) supporting sustainable agriculture; (3) facilitating ridge-to-reef management; and (4) supporting statewide terrestrial and marine spatial planning. Given the interest expressed by natural resource managers, we envision broad adoption of ES knowledge and decision support tools if knowledge and tools are tailored to the Hawaiian context and coupled with adequate outreach and training.
2011-01-01
Background Copy number aberrations (CNAs) are an important molecular signature in cancer initiation, development, and progression. However, these aberrations span a wide range of chromosomes, making it hard to distinguish cancer related genes from other genes that are not closely related to cancer but are located in broadly aberrant regions. With the current availability of high-resolution data sets such as single nucleotide polymorphism (SNP) microarrays, it has become an important issue to develop a computational method to detect driving genes related to cancer development located in the focal regions of CNAs. Results In this study, we introduce a novel method referred to as the wavelet-based identification of focal genomic aberrations (WIFA). The use of the wavelet analysis, because it is a multi-resolution approach, makes it possible to effectively identify focal genomic aberrations in broadly aberrant regions. The proposed method integrates multiple cancer samples so that it enables the detection of the consistent aberrations across multiple samples. We then apply this method to glioblastoma multiforme and lung cancer data sets from the SNP microarray platform. Through this process, we confirm the ability to detect previously known cancer related genes from both cancer types with high accuracy. Also, the application of this approach to a lung cancer data set identifies focal amplification regions that contain known oncogenes, though these regions are not reported using a recent CNAs detecting algorithm GISTIC: SMAD7 (chr18q21.1) and FGF10 (chr5p12). Conclusions Our results suggest that WIFA can be used to reveal cancer related genes in various cancer data sets. PMID:21569311
Novel AlInN/GaN integrated circuits operating up to 500 °C
NASA Astrophysics Data System (ADS)
Gaska, R.; Gaevski, M.; Jain, R.; Deng, J.; Islam, M.; Simin, G.; Shur, M.
2015-11-01
High electron concentration in 2DEG channel of AlInN/GaN devices is remarkably stable over a broad temperature range, enabling device operation above 500 °C. The developed IC technology is based on three key elements: (1) exceptional quality AlInN/GaN heterostructure with very high carrier concentration and mobility enables IC fast operation in a broad temperature range; (2) heterostructure field effect transistor approach t provides fully planar IC structure which is easy to scale and to combine with the other high temperature electronic components; (3) fabrication advancements including novel metallization scheme and high-K passivation/gate dielectrics enable high temperature operation. The feasibility of the developed technology was confirmed by fabrication and testing of the high temperature inverter and differential amplifier ICs using AlInN/GaN heterostructures. The developed ICs showed stable performance with unit-gain bandwidth above 1 MHz and internal response time 45 ns at temperatures as high as 500 °C.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Konopka, Allan
2009-05-15
Microbial ecology is a relatively young discipline within the field of microbiology. Its modern history spans just the past 60 years, and the field is defined by its emphasis on understanding the interactions of microbes with their environment, rather than their behavior under artificial laboratory conditions. Because microbes are ubiquitous, microbial ecologists study a broad diversity of habitats that range from aquatic to terrestrial to plant- or animal-associated. This has made it a challenge to identify unifying principles within the field. One approach is to recognize that although the activity of microbes in nature have effects at the macroscale, theymore » interact with their physical, chemical and biological milieu at a scale of micrometers. At this scale, several different microbial ecosystems can be defined, based upon association with particles, the presence of environmental gradients and the continuous availability of water. Principles applicable to microbial ecology reflect not only their population ecology and physiological ecology, but also their broad versatility and quantitative importance in the biosphere as biogeochemical catalysts and capacity for rapid physiological and evolutionary responses.« less
Liu, Shan; Jackson, Andrew; Beloor, Jagadish; Kumar, Priti; Sutton, Richard E
2015-09-01
Despite nearly three decades of research, a safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) has yet to be achieved. More recently, the discovery of highly potent anti-gp160 broadly neutralizing antibodies (bNAbs) has garnered renewed interest in using antibody-based prophylactic and therapeutic approaches. Here, we encoded bNAbs in first-generation adenoviral (ADV) vectors, which have the distinctive features of a large coding capacity and ease of propagation. A single intramuscular injection of ADV-vectorized bNAbs in humanized mice generated high serum levels of bNAbs that provided protection against multiple repeated challenges with a high dose of HIV-1, prevented depletion of peripheral CD4(+) T cells, and reduced plasma viral loads to below detection limits. Our results suggest that ADV vectors may be a viable option for the prophylactic and perhaps therapeutic use of bNAbs in humans.
Steam generator tube integrity flaw acceptance criteria
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cochet, B.
1997-02-01
The author discusses the establishment of a flaw acceptance criteria with respect to flaws in steam generator tubing. The problem is complicated because different countries take different approaches to the problem. The objectives in general are grouped in three broad areas: to avoid the unscheduled shutdown of the reactor during normal operation; to avoid tube bursts; to avoid excessive leak rates in the event of an accidental overpressure event. For each degradation mechanism in the tubes it is necessary to know answers to an array of questions, including: how well does NDT testing perform against this problem; how rapidly doesmore » such degradation develop; how well is this degradation mechanism understood. Based on the above information it is then possible to come up with a policy to look at flaw acceptance. Part of this criteria is a schedule for the frequency of in-service inspection and also a policy for when to plug flawed tubes. The author goes into a broad discussion of each of these points in his paper.« less
Reverse electrowetting as a new approach to high-power energy harvesting
Krupenkin, Tom; Taylor, J. Ashley
2011-01-01
Over the last decade electrical batteries have emerged as a critical bottleneck for portable electronics development. High-power mechanical energy harvesting can potentially provide a valuable alternative to the use of batteries, but, until now, a suitable mechanical-to-electrical energy conversion technology did not exist. Here we describe a novel mechanical-to-electrical energy conversion method based on the reverse electrowetting phenomenon. Electrical energy generation is achieved through the interaction of arrays of moving microscopic liquid droplets with novel nanometer-thick multilayer dielectric films. Advantages of this process include the production of high power densities, up to 103 W m−2; the ability to directly utilize a very broad range of mechanical forces and displacements; and the ability to directly output a broad range of currents and voltages, from several volts to tens of volts. These advantages make this method uniquely suited for high-power energy harvesting from a wide variety of environmental mechanical energy sources. PMID:21863015
Pankavich, S; Ortoleva, P
2010-06-01
The multiscale approach to N-body systems is generalized to address the broad continuum of long time and length scales associated with collective behaviors. A technique is developed based on the concept of an uncountable set of time variables and of order parameters (OPs) specifying major features of the system. We adopt this perspective as a natural extension of the commonly used discrete set of time scales and OPs which is practical when only a few, widely separated scales exist. The existence of a gap in the spectrum of time scales for such a system (under quasiequilibrium conditions) is used to introduce a continuous scaling and perform a multiscale analysis of the Liouville equation. A functional-differential Smoluchowski equation is derived for the stochastic dynamics of the continuum of Fourier component OPs. A continuum of spatially nonlocal Langevin equations for the OPs is also derived. The theory is demonstrated via the analysis of structural transitions in a composite material, as occurs for viral capsids and molecular circuits.
Dual-comb spectroscopy of laser-induced plasmas
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bergevin, Jenna; Wu, Tsung-Han; Yeak, Jeremy
Dual-comb spectroscopy has become a powerful spectroscopic technique in applications that rely on its broad spectral coverage combined with high frequency resolution capabilities. Experiments to date have primarily focused on detection and analysis of multiple gas species under semi-static conditions, with applications ranging from environmental monitoring of greenhouse gases to high resolution molecular spectroscopy. Here, we utilize dual-comb spectroscopy to demonstrate broadband, high-resolution, and time-resolved measurements in a laser induced plasma for the first time. As a first demonstration, we simultaneously detect trace amounts of Rb and K in solid samples with a single laser ablation shot, with transitions separatedmore » by over 6 THz (13 nm) and spectral resolution sufficient to resolve isotopic and ground state hyperfine splittings of the Rb D2 line. This new spectroscopic approach offers the broad spectral coverage found in the powerful techniques of laser-induced breakdown spectroscopy (LIBS) while providing the high-resolution and accuracy of cw laser-based spectroscopies.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Konopka, Allan
Microbial ecology is a relatively young discipline within the field of microbiology. Its modern history spans just the past 60 years, and the field is defined by its emphasis on understanding the interactions of microbes with their environment, rather than their behavior under artificial laboratory conditions. Because microbes are ubiquitous, microbial ecologists study a broad diversity of habitats that range from aquatic to terrestrial to plant- or animal-associated. This has made it a challenge to identify unifying principles within the field. One approach is to recognize that although the activity of microbes in nature have effects at the macroscale, theymore » interact with their physical, chemical and biological milieu at a scale of micrometers. At this scale, several different microbial ecosystems can be defined, based upon association with particles, the presence of environmental gradients and the continuous availability of water. Principles applicable to microbial ecology reflect not only their population ecology and physiological ecology, but also their broad versatility and quantitative importance in the biosphere as biogeochemical catalysts and capacity for rapid physiological and evolutionary responses.« less
Syed, Zeeshan; Saeed, Mohammed; Rubinfeld, Ilan
2010-01-01
For many clinical conditions, only a small number of patients experience adverse outcomes. Developing risk stratification algorithms for these conditions typically requires collecting large volumes of data to capture enough positive and negative for training. This process is slow, expensive, and may not be appropriate for new phenomena. In this paper, we explore different anomaly detection approaches to identify high-risk patients as cases that lie in sparse regions of the feature space. We study three broad categories of anomaly detection methods: classification-based, nearest neighbor-based, and clustering-based techniques. When evaluated on data from the National Surgical Quality Improvement Program (NSQIP), these methods were able to successfully identify patients at an elevated risk of mortality and rare morbidities following inpatient surgical procedures. PMID:21347083
Tumban, Ebenezer; Peabody, Julianne; Peabody, David S; Chackerian, Bryce
2011-01-01
Current human papillomavirus (HPV) vaccines that are based on virus-like particles (VLPs) of the major capsid protein L1 largely elicit HPV type-specific antibody responses. In contrast, immunization with the HPV minor capsid protein L2 elicits antibodies that are broadly cross-neutralizing, suggesting that a vaccine targeting L2 could provide more comprehensive protection against infection by diverse HPV types. However, L2-based immunogens typically elicit much lower neutralizing antibody titers than L1 VLPs. We previously showed that a conserved broadly neutralizing epitope near the N-terminus of L2 is highly immunogenic when displayed on the surface of VLPs derived from the bacteriophage PP7. Here, we report the development of a panel of PP7 VLP-based vaccines targeting L2 that protect mice from infection with carcinogenic and non-carcinogenic HPV types that infect the genital tract and skin. L2 peptides from eight different HPV types were displayed on the surface of PP7 bacteriophage VLPs. These recombinant L2 VLPs, both individually and in combination, elicited high-titer anti-L2 IgG serum antibodies. Immunized mice were protected from high dose infection with HPV pseudovirus (PsV) encapsidating a luciferase reporter. Mice immunized with 16L2 PP7 VLPs or 18L2 PP7 VLPs were nearly completely protected from both PsV16 and PsV18 challenge. Mice immunized with the mixture of eight L2 VLPs were strongly protected from genital challenge with PsVs representing eight diverse HPV types and cutaneous challenge with HPV5 PsV. VLP-display of a cross-neutralizing HPV L2 epitope is an effective approach for inducing high-titer protective neutralizing antibodies and is capable of offering protection from a spectrum of HPVs associated with cervical cancer as well as genital and cutaneous warts.
Orkaby, Brurya; Greenberger, Chaya
2015-03-01
To examine nurses' attitudes to holistic and biomedical approaches to health care and the correlation between the two and to explore the extent of recommending and using complementary and alternative medicine (CAM) by nurses and its correlation with attitudes toward the holistic approach to care. In this cross-sectional correlational study, a structured questionnaire was completed anonymously by 213 Israeli hospital-based nurses from various departments. Nurses perceived both approaches as critical to optimal health care: a positive correlation emerged of attitudes to the two approaches. Nurses recommended and used CAM extensively; most therapies were recommended and/or used by 70% or more of the respondents. Nurses with more positive attitudes toward holistic care tended to recommend and use CAM to a greater extent. Biomedical and holistic approaches are perceived by nurses to coexist within nursing professional boundaries and form a broad basis for optimal health care. Nurses' attitudes to the holistic approach appear to promote recommendation and/or use of CAM in practice. More training in CAM should be offered in nursing educational frameworks and research should continue to establish evidence for CAM's effectiveness. © The Author(s) 2014.
Recovery in the 21st Century: From Shame to Strength.
Gumbley, Stephen J
2016-01-01
Through the "war on drugs," the just-say-no campaign, and into the early years of this century, the overarching approach to substance use disorders (SUDs) called for a single outcome (abstinence) and a single methodology (spiritual connection with a higher power) as the remedy for SUDs. Those who did not become permanently abstinent or rejected the spiritual approach were seen as "not ready" or "in denial."A seismic shift in thinking about "addiction" and "recovery" began in earnest in the 1990s. In 2005, the Substance Abuse and Mental Health Services Administration brought together leaders of the treatment and recovery field for the historic National Summit on Recovery to develop broad-based consensus on guiding principles for recovery and elements of recovery-oriented systems of care.Major changes associated with the recovery-oriented approach include viewing SUDs as chronic, rather than acute, problems that require long-term support and focusing on recovery management rather than disease management. Complete abstinence is not an absolute requirement for wellness for all persons with SUDs. There are "many pathways to recovery," not only the 12-Step approach (White & Kurtz, 2006). Sustained recovery is self-directed and requires personal choices, the support of peers and allies, and community reinforcement as well as a strength-based approach and the use of research-based interventions. This Perspectives column addresses the historical context for the transformation toward a recovery-oriented system of care, highlights federal efforts to promote recovery-oriented approaches, and describes recovery-oriented terminology to reduce misconceptions, labeling, and stigmatization and promote recovery for individuals, families, and communities.
NASA Astrophysics Data System (ADS)
Ierodiaconou, Daniel; Schimel, Alexandre C. G.; Kennedy, David; Monk, Jacquomo; Gaylard, Grace; Young, Mary; Diesing, Markus; Rattray, Alex
2018-06-01
Habitat mapping data are increasingly being recognised for their importance in underpinning marine spatial planning. The ability to collect ultra-high resolution (cm) multibeam echosounder (MBES) data in shallow waters has facilitated understanding of the fine-scale distribution of benthic habitats in these areas that are often prone to human disturbance. Developing quantitative and objective approaches to integrate MBES data with ground observations for predictive modelling is essential for ensuring repeatability and providing confidence measures for habitat mapping products. Whilst supervised classification approaches are becoming more common, users are often faced with a decision whether to implement a pixel based (PB) or an object based (OB) image analysis approach, with often limited understanding of the potential influence of that decision on final map products and relative importance of data inputs to patterns observed. In this study, we apply an ensemble learning approach capable of integrating PB and OB Image Analysis from ultra-high resolution MBES bathymetry and backscatter data for mapping benthic habitats in Refuge Cove, a temperate coastal embayment in south-east Australia. We demonstrate the relative importance of PB and OB seafloor derivatives for the five broad benthic habitats that dominate the site. We found that OB and PB approaches performed well with differences in classification accuracy but not discernible statistically. However, a model incorporating elements of both approaches proved to be significantly more accurate than OB or PB methods alone and demonstrate the benefits of using MBES bathymetry and backscatter combined for class discrimination.
NASA Astrophysics Data System (ADS)
Salcedo-Sanz, S.
2016-10-01
Meta-heuristic algorithms are problem-solving methods which try to find good-enough solutions to very hard optimization problems, at a reasonable computation time, where classical approaches fail, or cannot even been applied. Many existing meta-heuristics approaches are nature-inspired techniques, which work by simulating or modeling different natural processes in a computer. Historically, many of the most successful meta-heuristic approaches have had a biological inspiration, such as evolutionary computation or swarm intelligence paradigms, but in the last few years new approaches based on nonlinear physics processes modeling have been proposed and applied with success. Non-linear physics processes, modeled as optimization algorithms, are able to produce completely new search procedures, with extremely effective exploration capabilities in many cases, which are able to outperform existing optimization approaches. In this paper we review the most important optimization algorithms based on nonlinear physics, how they have been constructed from specific modeling of a real phenomena, and also their novelty in terms of comparison with alternative existing algorithms for optimization. We first review important concepts on optimization problems, search spaces and problems' difficulty. Then, the usefulness of heuristics and meta-heuristics approaches to face hard optimization problems is introduced, and some of the main existing classical versions of these algorithms are reviewed. The mathematical framework of different nonlinear physics processes is then introduced as a preparatory step to review in detail the most important meta-heuristics based on them. A discussion on the novelty of these approaches, their main computational implementation and design issues, and the evaluation of a novel meta-heuristic based on Strange Attractors mutation will be carried out to complete the review of these techniques. We also describe some of the most important application areas, in broad sense, of meta-heuristics, and describe free-accessible software frameworks which can be used to make easier the implementation of these algorithms.
Attribution of Disturbances Causing Tree Mortality for the Continental U.S.
NASA Astrophysics Data System (ADS)
Wang, M.; Xu, C.; Allen, C. D.; McDowell, N. G.
2016-12-01
Broad-scale tree mortality has been frequently reported and documented to increase with warming climate and human activities. However, there is so far no general method to quantify the relative contributions of different disturbances on observed broad-scale tree mortality. In this study, we presented a framework to investigate the contribution of various disturbances causing tree mortality for 2000-2014 in the continental US. Our work is based on the high-resolution forest-loss data developed by Hansen et al. (2013). Firstly, fire-driven mortality was determined using the data from Monitoring Trends in Burn Severity (MTBS) project. Secondly, a landscape-pattern-recognition approach focusing on the differences of boundary complexity caused by natural and anthropogenic disturbances was developed to attribute harvest-driven mortality patches. Then, a drought threshold was determined through conducting an intensive literature survey for attribution of drought-driven mortality. Our results showed that we can correctly attribute 85% harvest-driven mortality as compared to Forest Inventory and Analysis (FIA) data. Based on Evaporative Stress Index (ESI), our literature survey suggests that most mortality events happened at extreme drought (37.7%), then severe (31.4%) and moderate (23.4%) drought. In total, 92.6% of drought-induced mortality events observed during 2000-2014 occurred at drought conditions of moderate or worse with corresponding ESI values ranging from -0.9 -2.49. Therefore, -0.9 will be used as the threshold to attribute drought-driven tree mortality. Overall, these results imply a great potential for using these methods to identify and attribute disturbances driving tree death at broad spatial scales.
Life is 3D: Boosting Spheroid Function for Tissue Engineering.
Laschke, Matthias W; Menger, Michael D
2017-02-01
Spheroids provide a 3D environment with intensive cell-cell contacts. As a result of their excellent regenerative properties and rapid progress in their high-throughput production, spheroids are increasingly suggested as building blocks for tissue engineering. In this review, we focus on innovative biotechnological approaches that increase the quality of spheroids for this specific type of application. These include in particular the fabrication of coculture spheroids, mimicking the complex morphology and physiological tasks of natural tissues. In vitro preconditioning under different culture conditions and incorporation of biomaterials improve the function of spheroids and their directed fusion into macrotissues of desired shapes. The continuous development of these sophisticated approaches may markedly contribute to a broad implementation of spheroid-based tissue engineering in future regenerative medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.
Expression proteomics study to determine metallodrug targets and optimal drug combinations.
Lee, Ronald F S; Chernobrovkin, Alexey; Rutishauser, Dorothea; Allardyce, Claire S; Hacker, David; Johnsson, Kai; Zubarev, Roman A; Dyson, Paul J
2017-05-08
The emerging technique termed functional identification of target by expression proteomics (FITExP) has been shown to identify the key protein targets of anti-cancer drugs. Here, we use this approach to elucidate the proteins involved in the mechanism of action of two ruthenium(II)-based anti-cancer compounds, RAPTA-T and RAPTA-EA in breast cancer cells, revealing significant differences in the proteins upregulated. RAPTA-T causes upregulation of multiple proteins suggesting a broad mechanism of action involving suppression of both metastasis and tumorigenicity. RAPTA-EA bearing a GST inhibiting ethacrynic acid moiety, causes upregulation of mainly oxidative stress related proteins. The approach used in this work could be applied to the prediction of effective drug combinations to test in cancer chemotherapy clinical trials.
He, Wei; Yurkevich, Igor V; Canham, Leigh T; Loni, Armando; Kaplan, Andrey
2014-11-03
We develop an analytical model based on the WKB approach to evaluate the experimental results of the femtosecond pump-probe measurements of the transmittance and reflectance obtained on thin membranes of porous silicon. The model allows us to retrieve a pump-induced nonuniform complex dielectric function change along the membrane depth. We show that the model fitting to the experimental data requires a minimal number of fitting parameters while still complying with the restriction imposed by the Kramers-Kronig relation. The developed model has a broad range of applications for experimental data analysis and practical implementation in the design of devices involving a spatially nonuniform dielectric function, such as in biosensing, wave-guiding, solar energy harvesting, photonics and electro-optical devices.
NASA Astrophysics Data System (ADS)
Ehrmann, Andrea; Blachowicz, Tomasz; Zghidi, Hafed
2015-05-01
Modelling hysteresis behaviour, as it can be found in a broad variety of dynamical systems, can be performed in different ways. An elementary approach, applied for a set of elementary cells, which uses only two possible states per cell, is the Ising model. While such Ising models allow for a simulation of many systems with sufficient accuracy, they nevertheless depict some typical features which must be taken into account with proper care, such as meta-stability or the externally applied field sweeping speed. This paper gives a general overview of recent results from Ising models from the perspective of a didactic model, based on a 2D spreadsheet analysis, which can be used also for solving general scientific problems where direct next-neighbour interactions take place.
Multi-pass transmission electron microscopy
Juffmann, Thomas; Koppell, Stewart A.; Klopfer, Brannon B.; ...
2017-05-10
Feynman once asked physicists to build better electron microscopes to be able to watch biology at work. While electron microscopes can now provide atomic resolution, electron beam induced specimen damage precludes high resolution imaging of sensitive materials, such as single proteins or polymers. Here, we use simulations to show that an electron microscope based on a multi-pass measurement protocol enables imaging of single proteins, without averaging structures over multiple images. While we demonstrate the method for particular imaging targets, the approach is broadly applicable and is expected to improve resolution and sensitivity for a range of electron microscopy imaging modalities,more » including, for example, scanning and spectroscopic techniques. The approach implements a quantum mechanically optimal strategy which under idealized conditions can be considered interaction-free.« less
Blueprinting macromolecular electronics.
Palma, Carlos-Andres; Samorì, Paolo
2011-06-01
Recently, by mastering either top-down or bottom-up approaches, tailor-made macromolecular nano-objects with semiconducting properties have been fabricated. These engineered nanostructures for organic electronics are based on conjugated systems predominantly made up of sp²-hybridized carbon, such as graphene nanoribbons. Here, we describe developments in a selection of these nanofabrication techniques, which include graphene carving, stimulus-induced synthesis of conjugated polymers and surface-assisted synthesis. We also assess their potential to reproduce chemically and spatially precise molecular arrangements, that is, molecular blueprints. In a broad context, the engineering of a molecular blueprint represents the fabrication of an integrated all-organic macromolecular electronic circuit. In this Perspective, we suggest chemical routes, as well as convergent on-surface synthesis and microfabrication approaches, for the ultimate goal of bringing the field closer to technology.
Emerging perspectives in social neuroscience and neuroeconomics of aging
Mather, Mara
2011-01-01
This article introduces the special issue of ‘Social Cognitive and Affective Neuroscience’ on Aging Research, and offers a broad conceptual and methodological framework for considering advances in life course research in social neuroscience and neuroeconomics. The authors highlight key areas of inquiry where aging research is raising new insights about how to conceptualize and examine critical questions about the links between cognition, emotion and motivation in social and economic behavior, as well as challenges that need to be addressed when taking a life course perspective in these fields. They also point to several emerging approaches that hold the potential for addressing these challenges, through bridging approaches from laboratory and population-based science, bridging inquiry across life stages and expanding measurement of core psychological phenotypes. PMID:21482573
Di Scala, Coralie; Fantini, Jacques
2017-01-01
In eukaryotic cells, cholesterol is an important regulator of a broad range of membrane proteins, including receptors, transporters, and ion channels. Understanding how cholesterol interacts with membrane proteins is a difficult task because structural data of these proteins complexed with cholesterol are scarce. Here, we describe a dual approach based on in silico studies of protein-cholesterol interactions, combined with physico-chemical measurements of protein insertion into cholesterol-containing monolayers. Our algorithm is validated through careful analysis of the effect of key mutations within and outside the predicted cholesterol-binding site. Our method is illustrated by a complete analysis of cholesterol-binding to Alzheimer's β-amyloid peptide, a protein that penetrates the plasma membrane of brain cells through a cholesterol-dependent process.
Using Markov state models to study self-assembly
NASA Astrophysics Data System (ADS)
Perkett, Matthew R.; Hagan, Michael F.
2014-06-01
Markov state models (MSMs) have been demonstrated to be a powerful method for computationally studying intramolecular processes such as protein folding and macromolecular conformational changes. In this article, we present a new approach to construct MSMs that is applicable to modeling a broad class of multi-molecular assembly reactions. Distinct structures formed during assembly are distinguished by their undirected graphs, which are defined by strong subunit interactions. Spatial inhomogeneities of free subunits are accounted for using a recently developed Gaussian-based signature. Simplifications to this state identification are also investigated. The feasibility of this approach is demonstrated on two different coarse-grained models for virus self-assembly. We find good agreement between the dynamics predicted by the MSMs and long, unbiased simulations, and that the MSMs can reduce overall simulation time by orders of magnitude.
Friedrich, Torben; Rahmann, Sven; Weigel, Wilfried; Rabsch, Wolfgang; Fruth, Angelika; Ron, Eliora; Gunzer, Florian; Dandekar, Thomas; Hacker, Jörg; Müller, Tobias; Dobrindt, Ulrich
2010-10-21
The Enterobacteriaceae comprise a large number of clinically relevant species with several individual subspecies. Overlapping virulence-associated gene pools and the high overall genome plasticity often interferes with correct enterobacterial strain typing and risk assessment. Array technology offers a fast, reproducible and standardisable means for bacterial typing and thus provides many advantages for bacterial diagnostics, risk assessment and surveillance. The development of highly discriminative broad-range microbial diagnostic microarrays remains a challenge, because of marked genome plasticity of many bacterial pathogens. We developed a DNA microarray for strain typing and detection of major antimicrobial resistance genes of clinically relevant enterobacteria. For this purpose, we applied a global genome-wide probe selection strategy on 32 available complete enterobacterial genomes combined with a regression model for pathogen classification. The discriminative power of the probe set was further tested in silico on 15 additional complete enterobacterial genome sequences. DNA microarrays based on the selected probes were used to type 92 clinical enterobacterial isolates. Phenotypic tests confirmed the array-based typing results and corroborate that the selected probes allowed correct typing and prediction of major antibiotic resistances of clinically relevant Enterobacteriaceae, including the subspecies level, e.g. the reliable distinction of different E. coli pathotypes. Our results demonstrate that the global probe selection approach based on longest common factor statistics as well as the design of a DNA microarray with a restricted set of discriminative probes enables robust discrimination of different enterobacterial variants and represents a proof of concept that can be adopted for diagnostics of a wide range of microbial pathogens. Our approach circumvents misclassifications arising from the application of virulence markers, which are highly affected by horizontal gene transfer. Moreover, a broad range of pathogens have been covered by an efficient probe set size enabling the design of high-throughput diagnostics.
Ievlev, Anton; Kalinin, Sergei V.
2015-05-28
Ferroelectric materials are broadly considered for information storage due to extremely high storage and information processing densities they enable. To date, ferroelectric based data storage has invariably relied on formation of cylindrical domains, allowing for binary information encoding. Here we demonstrate and explore the potential of high-density encoding based on domain morphology. We explore the domain morphogenesis during the tip-induced polarization switching by sequences of positive and negative pulses in a lithium niobate single-crystal and demonstrate the principal of information coding by shape and size of the domains. We applied cross-correlation and neural network approaches for recognition of the switchingmore » sequence by the shape of the resulting domains and establish optimal parameters for domain shape recognition. These studies both provide insight into the highly non-trivial mechanism of domain switching and potentially establish a new paradigm for multilevel information storage and content retrieval memories. Furthermore, this approach opens a pathway to exploration of domain switching mechanisms via shape analysis.« less
Li, Haiqing; Song, Sing I; Song, Ga Young; Kim, Il
2014-02-01
Carbon nanostructures (CNSs) such as carbon nanotubes, graphene sheets, and nanodiamonds provide an important type of substrate for constructing a variety of hybrid nanomaterials. However, their intrinsic chemistry-inert surfaces make it indispensable to pre-functionalize them prior to immobilizing additional components onto their surfaces. Currently developed strategies for functionalizing CNSs include covalent and non-covalent approaches. Conventional covalent treatments often damage the structure integrity of carbon surfaces and adversely affect their physical properties. In contrast, the non-covalent approach offers a non-destructive way to modify CNSs with desired functional surfaces, while reserving their intrinsic properties. Thus far, a number of surface modifiers including aromatic compounds, small-molecular surfactants, amphiphilic polymers, and biomacromolecules have been developed to non-covalently functionalize CNS surfaces. Mediated by these surface modifiers, various functional components such as organic species and inorganic nanoparticles were further decorated onto their surfaces, resulting in versatile carbon-based hybrid nanomaterials with broad applications in chemical engineering and biomedical areas. In this review, the recent advances in the generation of such hybrid nanostructures based on non-covalently functionalized CNSs will be reviewed.
[Music-based intervention in children].
Kiese-Himmel, Christiane
2012-01-01
Music-based interventions with children are an effective method in health and sickness treatment and in education systems. The engagement with music enables positive transfer effects on extra-musical developmental domains. Music therapy was applied primarily as a practically-oriented scientific discipline both within the framework of a multi-modal therapy approach as one treatment component and focused specifically on children with emotional disorders within a somatic therapy concept and in rehabilitation. The following narrative overview will present music therapy's working basis, treatment goals, and select outcome research in children from 2005-2010. There currently exists a substantial lack, even within empirical research, in relation to the application of music therapy to children. This is an opportunity to initiate a broad range of study for the future. Current challenges and opportunities in scientific, music-based intervention in the paediatric population lie in the concretization of differential indications (both in intervention approach and duration), replicable comparative therapy (alternated treatment-design), the application of a music-therapeutic placebo requirement, as well as in the verification and analysis of specific music therapeutic mechanisms.
AVC: Selecting discriminative features on basis of AUC by maximizing variable complementarity.
Sun, Lei; Wang, Jun; Wei, Jinmao
2017-03-14
The Receiver Operator Characteristic (ROC) curve is well-known in evaluating classification performance in biomedical field. Owing to its superiority in dealing with imbalanced and cost-sensitive data, the ROC curve has been exploited as a popular metric to evaluate and find out disease-related genes (features). The existing ROC-based feature selection approaches are simple and effective in evaluating individual features. However, these approaches may fail to find real target feature subset due to their lack of effective means to reduce the redundancy between features, which is essential in machine learning. In this paper, we propose to assess feature complementarity by a trick of measuring the distances between the misclassified instances and their nearest misses on the dimensions of pairwise features. If a misclassified instance and its nearest miss on one feature dimension are far apart on another feature dimension, the two features are regarded as complementary to each other. Subsequently, we propose a novel filter feature selection approach on the basis of the ROC analysis. The new approach employs an efficient heuristic search strategy to select optimal features with highest complementarities. The experimental results on a broad range of microarray data sets validate that the classifiers built on the feature subset selected by our approach can get the minimal balanced error rate with a small amount of significant features. Compared with other ROC-based feature selection approaches, our new approach can select fewer features and effectively improve the classification performance.
Stone-Weiss, Nicholas; Pierce, Eric M; Youngman, Randall E; Gulbiten, Ozgur; Smith, Nicholas J; Du, Jincheng; Goel, Ashutosh
2018-01-01
The past decade has witnessed a significant upsurge in the development of borate and borosilicate based resorbable bioactive glasses owing to their faster degradation rate in comparison to their silicate counterparts. However, due to our lack of understanding about the fundamental science governing the aqueous corrosion of these glasses, most of the borate/borosilicate based bioactive glasses reported in the literature have been designed by "trial-and-error" approach. With an ever-increasing demand for their application in treating a broad spectrum of non-skeletal health problems, it is becoming increasingly difficult to design advanced glass formulations using the same conventional approach. Therefore, a paradigm shift from the "trial-and-error" approach to "materials-by-design" approach is required to develop new-generations of bioactive glasses with controlled release of functional ions tailored for specific patients and disease states, whereby material functions and properties can be predicted from first principles. Realizing this goal, however, requires a thorough understanding of the complex sequence of reactions that control the dissolution kinetics of bioactive glasses and the structural drivers that govern them. While there is a considerable amount of literature published on chemical dissolution behavior and apatite-forming ability of potentially bioactive glasses, the majority of this literature has been produced on silicate glass chemistries using different experimental and measurement protocols. It follows that inter-comparison of different datasets reveals inconsistencies between experimental groups. There are also some major experimental challenges or choices that need to be carefully navigated to unearth the mechanisms governing the chemical degradation behavior and kinetics of boron-containing bioactive glasses, and to accurately determine the composition-structure-property relationships. In order to address these challenges, a simplified borosilicate based model melt-quenched bioactive glass system has been studied to depict the impact of thermal history on its molecular structure and dissolution behavior in water. It has been shown that the methodology of quenching of the glass melt impacts the dissolution rate of the studied glasses by 1.5×-3× depending on the changes induced in their molecular structure due to variation in thermal history. Further, a recommendation has been made to study dissolution behavior of bioactive glasses using surface area of the sample - to - volume of solution (SA/V) approach instead of the currently followed mass of sample - to - volume of solution approach. The structural and chemical dissolution data obtained from bioactive glasses following the approach presented in this paper can be used to develop the structural descriptors and potential energy functions over a broad range of bioactive glass compositions. Realizing the goal of designing third generation bioactive glasses requires a thorough understanding of the complex sequence of reactions that control their rate of degradation (in physiological fluids) and the structural drivers that control them. In this article, we have highlighted some major experimental challenges and choices that need to be carefully navigated in order to unearth the mechanisms governing the chemical dissolution behavior of borosilicate based bioactive glasses. The proposed experimental approach allows us to gain a new level of conceptual understanding about the composition-structure-property relationships in these glass systems, which can be applied to attain a significant leap in designing borosilicate based bioactive glasses with controlled dissolution rates tailored for specific patient and disease states. Copyright © 2017 Acta Materialia Inc. All rights reserved.
Comparing Information Access Approaches.
ERIC Educational Resources Information Center
Chalmers, Matthew
1999-01-01
Presents a broad view of information access, drawing from philosophy and semiology in constructing a framework for comparative discussion that is used to examine the information representations that underlie four approaches to information access--information retrieval, workflow, collaborative filtering, and the path model. Contains 32 references.…
Functional Responses of Salt Marsh Microbial Communities to Long-Term Nutrient Enrichment
Graves, Christopher J.; Makrides, Elizabeth J.; Schmidt, Victor T.; Giblin, Anne E.; Cardon, Zoe G.
2016-01-01
ABSTRACT Environmental nutrient enrichment from human agricultural and waste runoff could cause changes to microbial communities that allow them to capitalize on newly available resources. Currently, the response of microbial communities to nutrient enrichment remains poorly understood, and, while some studies have shown no clear changes in community composition in response to heavy nutrient loading, others targeting specific genes have demonstrated clear impacts. In this study, we compared functional metagenomic profiles from sediment samples taken along two salt marsh creeks, one of which was exposed for more than 40 years to treated sewage effluent at its head. We identified strong and consistent increases in the relative abundance of microbial genes related to each of the biochemical steps in the denitrification pathway at enriched sites. Despite fine-scale local increases in the abundance of denitrification-related genes, the overall community structures based on broadly defined functional groups and taxonomic annotations were similar and varied with other environmental factors, such as salinity, which were common to both creeks. Homology-based taxonomic assignments of nitrous oxide reductase sequences in our data show that increases are spread over a broad taxonomic range, thus limiting detection from taxonomic data alone. Together, these results illustrate a functionally targeted yet taxonomically broad response of microbial communities to anthropogenic nutrient loading, indicating some resolution to the apparently conflicting results of existing studies on the impacts of nutrient loading in sediment communities. IMPORTANCE In this study, we used environmental metagenomics to assess the response of microbial communities in estuarine sediments to long-term, nutrient-rich sewage effluent exposure. Unlike previous studies, which have mainly characterized communities based on taxonomic data or primer-based amplification of specific target genes, our whole-genome metagenomics approach allowed an unbiased assessment of the abundance of denitrification-related genes across the entire community. We identified strong and consistent increases in the relative abundance of gene sequences related to denitrification pathways across a broad phylogenetic range at sites exposed to long-term nutrient addition. While further work is needed to determine the consequences of these community responses in regulating environmental nutrient cycles, the increased abundance of bacteria harboring denitrification genes suggests that such processes may be locally upregulated. In addition, our results illustrate how whole-genome metagenomics combined with targeted hypothesis testing can reveal fine-scale responses of microbial communities to environmental disturbance. PMID:26944843
Functional Responses of Salt Marsh Microbial Communities to Long-Term Nutrient Enrichment.
Graves, Christopher J; Makrides, Elizabeth J; Schmidt, Victor T; Giblin, Anne E; Cardon, Zoe G; Rand, David M
2016-05-01
Environmental nutrient enrichment from human agricultural and waste runoff could cause changes to microbial communities that allow them to capitalize on newly available resources. Currently, the response of microbial communities to nutrient enrichment remains poorly understood, and, while some studies have shown no clear changes in community composition in response to heavy nutrient loading, others targeting specific genes have demonstrated clear impacts. In this study, we compared functional metagenomic profiles from sediment samples taken along two salt marsh creeks, one of which was exposed for more than 40 years to treated sewage effluent at its head. We identified strong and consistent increases in the relative abundance of microbial genes related to each of the biochemical steps in the denitrification pathway at enriched sites. Despite fine-scale local increases in the abundance of denitrification-related genes, the overall community structures based on broadly defined functional groups and taxonomic annotations were similar and varied with other environmental factors, such as salinity, which were common to both creeks. Homology-based taxonomic assignments of nitrous oxide reductase sequences in our data show that increases are spread over a broad taxonomic range, thus limiting detection from taxonomic data alone. Together, these results illustrate a functionally targeted yet taxonomically broad response of microbial communities to anthropogenic nutrient loading, indicating some resolution to the apparently conflicting results of existing studies on the impacts of nutrient loading in sediment communities. In this study, we used environmental metagenomics to assess the response of microbial communities in estuarine sediments to long-term, nutrient-rich sewage effluent exposure. Unlike previous studies, which have mainly characterized communities based on taxonomic data or primer-based amplification of specific target genes, our whole-genome metagenomics approach allowed an unbiased assessment of the abundance of denitrification-related genes across the entire community. We identified strong and consistent increases in the relative abundance of gene sequences related to denitrification pathways across a broad phylogenetic range at sites exposed to long-term nutrient addition. While further work is needed to determine the consequences of these community responses in regulating environmental nutrient cycles, the increased abundance of bacteria harboring denitrification genes suggests that such processes may be locally upregulated. In addition, our results illustrate how whole-genome metagenomics combined with targeted hypothesis testing can reveal fine-scale responses of microbial communities to environmental disturbance. Copyright © 2016 Graves et al.
Chutrakul, Chanikul; Khaokhajorn, Pratoomporn; Auncharoen, Patchanee; Boonruengprapa, Tanapong; Mongkolporn, Orarat
2013-01-01
Severe chili anthracnose disease in Thailand is caused by Colletotrichum gloeosporioides and C. capsici. To discover anti-anthracnose substances we developed an efficient dual-fluorescent labeling bioassay based on a microdilution approach. Indicator strains used in the assay were constructed by integrating synthetic green fluorescent protein (sGFP) and Discosoma sp. red fluorescent protein (DsRedExp) genes into the genomes of C. gloeosporioides or C. capsici respectively. Survival of co-spore cultures in the presence of inhibitors was determined by the expression levels of these fluorescent proteins. This developed assay has high potential for utilization in the investigation of selective inhibition activity to either one of the pathogens as well as the broad-range inhibitory effect against both pathogens. The value of using the dual-fluorescent assay is rapid, reliable, and consistent identification of anti-anthracnose agents. Most of all, the assay enables the identification of specific inhibitors under the co-cultivation condition.
RootGraph: a graphic optimization tool for automated image analysis of plant roots
Cai, Jinhai; Zeng, Zhanghui; Connor, Jason N.; Huang, Chun Yuan; Melino, Vanessa; Kumar, Pankaj; Miklavcic, Stanley J.
2015-01-01
This paper outlines a numerical scheme for accurate, detailed, and high-throughput image analysis of plant roots. In contrast to existing root image analysis tools that focus on root system-average traits, a novel, fully automated and robust approach for the detailed characterization of root traits, based on a graph optimization process is presented. The scheme, firstly, distinguishes primary roots from lateral roots and, secondly, quantifies a broad spectrum of root traits for each identified primary and lateral root. Thirdly, it associates lateral roots and their properties with the specific primary root from which the laterals emerge. The performance of this approach was evaluated through comparisons with other automated and semi-automated software solutions as well as against results based on manual measurements. The comparisons and subsequent application of the algorithm to an array of experimental data demonstrate that this method outperforms existing methods in terms of accuracy, robustness, and the ability to process root images under high-throughput conditions. PMID:26224880
NASA Astrophysics Data System (ADS)
Moffitt, Elizabeth A.; Punt, André E.; Holsman, Kirstin; Aydin, Kerim Y.; Ianelli, James N.; Ortiz, Ivonne
2016-12-01
Multi-species models can improve our understanding of the effects of fishing so that it is possible to make informed and transparent decisions regarding fishery impacts. Broad application of multi-species assessment models to support ecosystem-based fisheries management (EBFM) requires the development and testing of multi-species biological reference points (MBRPs) for use in harvest-control rules. We outline and contrast several possible MBRPs that range from those that can be readily used in current frameworks to those belonging to a broader EBFM context. We demonstrate each of the possible MBRPs using a simple two species model, motivated by walleye pollock (Gadus chalcogrammus) and Pacific cod (Gadus macrocephalus) in the eastern Bering Sea, to illustrate differences among methods. The MBRPs we outline each differ in how they approach the multiple, potentially conflicting management objectives and trade-offs of EBFM. These options for MBRPs allow multi-species models to be readily adapted for EBFM across a diversity of management mandates and approaches.
Hierarchical multivariate covariance analysis of metabolic connectivity.
Carbonell, Felix; Charil, Arnaud; Zijdenbos, Alex P; Evans, Alan C; Bedell, Barry J
2014-12-01
Conventional brain connectivity analysis is typically based on the assessment of interregional correlations. Given that correlation coefficients are derived from both covariance and variance, group differences in covariance may be obscured by differences in the variance terms. To facilitate a comprehensive assessment of connectivity, we propose a unified statistical framework that interrogates the individual terms of the correlation coefficient. We have evaluated the utility of this method for metabolic connectivity analysis using [18F]2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. As an illustrative example of the utility of this approach, we examined metabolic connectivity in angular gyrus and precuneus seed regions of mild cognitive impairment (MCI) subjects with low and high β-amyloid burdens. This new multivariate method allowed us to identify alterations in the metabolic connectome, which would not have been detected using classic seed-based correlation analysis. Ultimately, this novel approach should be extensible to brain network analysis and broadly applicable to other imaging modalities, such as functional magnetic resonance imaging (MRI).
NASA Astrophysics Data System (ADS)
Shrestha, K.; Gofryk, K.
2018-04-01
We have designed and developed a new experimental setup, based on the 3ω method, to measure thermal conductivity, heat capacity, and electrical resistivity of a variety of samples in a broad temperature range (2-550 K) and under magnetic fields up to 9 T. The validity of this method is tested by measuring various types of metallic (copper, platinum, and constantan) and insulating (SiO2) materials, which have a wide range of thermal conductivity values (1-400 W m-1 K-1). We have successfully employed this technique for measuring the thermal conductivity of two actinide single crystals: uranium dioxide and uranium nitride. This new experimental approach for studying nuclear materials will help us to advance reactor fuel development and understanding. We have also shown that this experimental setup can be adapted to the Physical Property Measurement System (Quantum Design) environment and/or other cryocooler systems.
Xu, Rosalind J; Blasiak, Bartosz; Cho, Minhaeng; Layfield, Joshua P; Londergan, Casey H
2018-05-17
A quantitative connection between molecular dynamics simulations and vibrational spectroscopy of probe-labeled systems would enable direct translation of experimental data into structural and dynamical information. To constitute this connection, all-atom molecular dynamics (MD) simulations were performed for two SCN probe sites (solvent-exposed and buried) in a calmodulin-target peptide complex. Two frequency calculation approaches with substantial nonelectrostatic components, a quantum mechanics/molecular mechanics (QM/MM)-based technique and a solvatochromic fragment potential (SolEFP) approach, were used to simulate the infrared probe line shapes. While QM/MM results disagreed with experiment, SolEFP results matched experimental frequencies and line shapes and revealed the physical and dynamic bases for the observed spectroscopic behavior. The main determinant of the CN probe frequency is the exchange repulsion between the probe and its local structural neighbors, and there is a clear dynamic explanation for the relatively broad probe line shape observed at the "buried" probe site. This methodology should be widely applicable to vibrational probes in many environments.
Alpha7 nicotinic receptors as novel therapeutic targets for inflammation-based diseases
Bencherif, Merouane; Lippiello, Patrick M.; Lucas, Rudolf; Marrero, Mario B.
2013-01-01
In recent years the etiopathology of a number of debilitating diseases such as type 2 diabetes, arthritis, atherosclerosis, psoriasis, asthma, cystic fibrosis, sepsis, and ulcerative colitis has increasingly been linked to runaway cytokine-mediated inflammation. Cytokine-based therapeutic agents play a major role in the treatment of these diseases. However, the temporospatial changes in various cytokines are still poorly understood and attempts to date have focused on the inhibition of specific cytokines such as TNF-α. As an alternative approach, a number of preclinical studies have confirmed the therapeutic potential of targeting alpha7 nicotinic acetylcholine receptor-mediated anti-inflammatory effects through modulation of proinflammatory cytokines. This “cholinergic anti-inflammatory pathway” modulates the immune system through cholinergic mechanisms that act on alpha7 receptors expressed on macrophages and immune cells. If the preclinical findings translate into human efficacy this approach could potentially provide new therapies for treating a broad array of intractable diseases and conditions with inflammatory components. PMID:20953658
Mixture-based gatekeeping procedures in adaptive clinical trials.
Kordzakhia, George; Dmitrienko, Alex; Ishida, Eiji
2018-01-01
Clinical trials with data-driven decision rules often pursue multiple clinical objectives such as the evaluation of several endpoints or several doses of an experimental treatment. These complex analysis strategies give rise to "multivariate" multiplicity problems with several components or sources of multiplicity. A general framework for defining gatekeeping procedures in clinical trials with adaptive multistage designs is proposed in this paper. The mixture method is applied to build a gatekeeping procedure at each stage and inferences at each decision point (interim or final analysis) are performed using the combination function approach. An advantage of utilizing the mixture method is that it enables powerful gatekeeping procedures applicable to a broad class of settings with complex logical relationships among the hypotheses of interest. Further, the combination function approach supports flexible data-driven decisions such as a decision to increase the sample size or remove a treatment arm. The paper concludes with a clinical trial example that illustrates the methodology by applying it to develop an adaptive two-stage design with a mixture-based gatekeeping procedure.
Liquid Chromatography-Mass Spectrometry-based Quantitative Proteomics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xie, Fang; Liu, Tao; Qian, Weijun
2011-07-22
Liquid chromatography-mass spectrometry (LC-MS)-based quantitative proteomics has become increasingly applied for a broad range of biological applications due to growing capabilities for broad proteome coverage and good accuracy in quantification. Herein, we review the current LC-MS-based quantification methods with respect to their advantages and limitations, and highlight their potential applications.
Fast and accurate grid representations for atom-based docking with partner flexibility.
de Vries, Sjoerd J; Zacharias, Martin
2017-06-30
Macromolecular docking methods can broadly be divided into geometric and atom-based methods. Geometric methods use fast algorithms that operate on simplified, grid-like molecular representations, while atom-based methods are more realistic and flexible, but far less efficient. Here, a hybrid approach of grid-based and atom-based docking is presented, combining precalculated grid potentials with neighbor lists for fast and accurate calculation of atom-based intermolecular energies and forces. The grid representation is compatible with simultaneous multibody docking and can tolerate considerable protein flexibility. When implemented in our docking method ATTRACT, grid-based docking was found to be ∼35x faster. With the OPLSX forcefield instead of the ATTRACT coarse-grained forcefield, the average speed improvement was >100x. Grid-based representations may allow atom-based docking methods to explore large conformational spaces with many degrees of freedom, such as multiple macromolecules including flexibility. This increases the domain of biological problems to which docking methods can be applied. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Designing a broad-spectrum integrative approach for cancer prevention and treatment.
Block, Keith I; Gyllenhaal, Charlotte; Lowe, Leroy; Amedei, Amedeo; Amin, A R M Ruhul; Amin, Amr; Aquilano, Katia; Arbiser, Jack; Arreola, Alexandra; Arzumanyan, Alla; Ashraf, S Salman; Azmi, Asfar S; Benencia, Fabian; Bhakta, Dipita; Bilsland, Alan; Bishayee, Anupam; Blain, Stacy W; Block, Penny B; Boosani, Chandra S; Carey, Thomas E; Carnero, Amancio; Carotenuto, Marianeve; Casey, Stephanie C; Chakrabarti, Mrinmay; Chaturvedi, Rupesh; Chen, Georgia Zhuo; Chen, Helen; Chen, Sophie; Chen, Yi Charlie; Choi, Beom K; Ciriolo, Maria Rosa; Coley, Helen M; Collins, Andrew R; Connell, Marisa; Crawford, Sarah; Curran, Colleen S; Dabrosin, Charlotta; Damia, Giovanna; Dasgupta, Santanu; DeBerardinis, Ralph J; Decker, William K; Dhawan, Punita; Diehl, Anna Mae E; Dong, Jin-Tang; Dou, Q Ping; Drew, Janice E; Elkord, Eyad; El-Rayes, Bassel; Feitelson, Mark A; Felsher, Dean W; Ferguson, Lynnette R; Fimognari, Carmela; Firestone, Gary L; Frezza, Christian; Fujii, Hiromasa; Fuster, Mark M; Generali, Daniele; Georgakilas, Alexandros G; Gieseler, Frank; Gilbertson, Michael; Green, Michelle F; Grue, Brendan; Guha, Gunjan; Halicka, Dorota; Helferich, William G; Heneberg, Petr; Hentosh, Patricia; Hirschey, Matthew D; Hofseth, Lorne J; Holcombe, Randall F; Honoki, Kanya; Hsu, Hsue-Yin; Huang, Gloria S; Jensen, Lasse D; Jiang, Wen G; Jones, Lee W; Karpowicz, Phillip A; Keith, W Nicol; Kerkar, Sid P; Khan, Gazala N; Khatami, Mahin; Ko, Young H; Kucuk, Omer; Kulathinal, Rob J; Kumar, Nagi B; Kwon, Byoung S; Le, Anne; Lea, Michael A; Lee, Ho-Young; Lichtor, Terry; Lin, Liang-Tzung; Locasale, Jason W; Lokeshwar, Bal L; Longo, Valter D; Lyssiotis, Costas A; MacKenzie, Karen L; Malhotra, Meenakshi; Marino, Maria; Martinez-Chantar, Maria L; Matheu, Ander; Maxwell, Christopher; McDonnell, Eoin; Meeker, Alan K; Mehrmohamadi, Mahya; Mehta, Kapil; Michelotti, Gregory A; Mohammad, Ramzi M; Mohammed, Sulma I; Morre, D James; Muralidhar, Vinayak; Muqbil, Irfana; Murphy, Michael P; Nagaraju, Ganji Purnachandra; Nahta, Rita; Niccolai, Elena; Nowsheen, Somaira; Panis, Carolina; Pantano, Francesco; Parslow, Virginia R; Pawelec, Graham; Pedersen, Peter L; Poore, Brad; Poudyal, Deepak; Prakash, Satya; Prince, Mark; Raffaghello, Lizzia; Rathmell, Jeffrey C; Rathmell, W Kimryn; Ray, Swapan K; Reichrath, Jörg; Rezazadeh, Sarallah; Ribatti, Domenico; Ricciardiello, Luigi; Robey, R Brooks; Rodier, Francis; Rupasinghe, H P Vasantha; Russo, Gian Luigi; Ryan, Elizabeth P; Samadi, Abbas K; Sanchez-Garcia, Isidro; Sanders, Andrew J; Santini, Daniele; Sarkar, Malancha; Sasada, Tetsuro; Saxena, Neeraj K; Shackelford, Rodney E; Shantha Kumara, H M C; Sharma, Dipali; Shin, Dong M; Sidransky, David; Siegelin, Markus David; Signori, Emanuela; Singh, Neetu; Sivanand, Sharanya; Sliva, Daniel; Smythe, Carl; Spagnuolo, Carmela; Stafforini, Diana M; Stagg, John; Subbarayan, Pochi R; Sundin, Tabetha; Talib, Wamidh H; Thompson, Sarah K; Tran, Phuoc T; Ungefroren, Hendrik; Vander Heiden, Matthew G; Venkateswaran, Vasundara; Vinay, Dass S; Vlachostergios, Panagiotis J; Wang, Zongwei; Wellen, Kathryn E; Whelan, Richard L; Yang, Eddy S; Yang, Huanjie; Yang, Xujuan; Yaswen, Paul; Yedjou, Clement; Yin, Xin; Zhu, Jiyue; Zollo, Massimo
2015-12-01
Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Verkoczy, Laurent
2018-01-01
A vaccine that can effectively prevent HIV-1 transmission remains paramount to ending the HIV pandemic, but to do so, will likely need to induce broad neutralizing antibody (bnAb) responses. A major technical hurdle towards achieving this goal has been a shortage of animal models with the ability to systematically pinpoint roadblocks to bnAb induction and to rank vaccine strategies based on their ability to stimulate bnAb development. Over the past six years, immunoglobulin (Ig) knock-in (KI) technology has been leveraged to express bnAbs in mice, an approach that has enabled elucidation of various B-cell tolerance mechanisms limiting bnAb production and evaluation of strategies to circumvent such processes. From these studies, in conjunction with the wealth of information recently obtained regarding the evolutionary pathways and paratopes/epitopes of multiple bnAbs, it has become clear that the very features of bnAbs desired for their function will be problematic to elicit by traditional vaccine paradigms, necessitating more iterative testing of new vaccine concepts. To meet this need, novel bnAb KI models have now been engineered to express either inferred pre-rearranged V(D)J exons (or unrearranged germline V, D, or J segments that can be assembled into functional rearranged V(D)J exons) encoding predecessors of mature bnAbs One encouraging approach that has materialized from studies using such newer models is sequential administration of immunogens designed to bind progressively more mature bnAb predecessors. In this review, insights into the regulation and induction of bnAbs based on the use of KI models will be discussed, as will new Ig KI approaches for higher-throughput production and/or altering expression of bnAbs in vivo, so as to further enable vaccine-guided bnAb induction studies. PMID:28413022
Hollow latex particles: synthesis and applications.
McDonald, Charles J; Devon, Michael J
2002-12-02
One of the major developments in emulsion polymerization over the last two decades has been the ability to make hollow latex particles. This has contributed many fundamental insights into the synthesis and the development of structure in particles. Hollow latex particles also enhance the performance of industrial coatings and potentially are useful in other technologies such as microencapsulation and controlled release. Ever since the publication of the initial process patents describing these particles, there has been a global R&D effort to extend the synthetic techniques and applications. One prominent synthetic approach to hollow particles is based on osmotic swelling. This dominates the literature, and usually starts with the synthesis of a structured latex particle containing an ionizable core that is subsequently expanded with the addition of base. Fundamental to this approach are a sophisticated control of transport phenomena, chemical reactivity within the particle, and the thermoplastic properties of the polymer shell. Hydrocarbon encapsulation technology has also been employed to make hollow latex particles. One approach involves a dispersed ternary system that balances transport, conversion kinetics, and phase separation variables to achieve the hollow morphology. Other techniques, including the use of blowing agents, are also present in the literature. The broad range of approaches that affords particles with a hollow structure demonstrates the unique flexibility of the emulsion polymerization process.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Markmann, Sergej, E-mail: sergej.markmann@ruhr-uni-bochum.de; Nong, Hanond, E-mail: nong.hanond@ruhr-uni-bochum.de; Hekmat, Negar
2015-09-14
We demonstrate by injection seeding that the spectral emission of a terahertz (THz) quantum cascade laser (QCL) can be modified with broad-band THz pulses whose bandwidths are greater than the QCL bandwidth. Two broad-band THz pulses delayed in time imprint a modulation on the single THz pulse spectrum. The resulting spectrum is used to injection seed the THz QCL. By varying the time delay between the THz pulses, the amplitude distribution of the QCL longitudinal modes is modified. By applying this approach, the QCL emission is reversibly switched from multi-mode to single mode emission.
Open University Environmental Education and Training.
ERIC Educational Resources Information Center
Blackmore, Christine
1996-01-01
Describes the approach to environmental education courses at Open University. Includes broad course content, team teaching approach, and philosophy of reorienting education towards sustainable development. Course material for open learning includes self-contained study packs as well as course texts, video, audio, and computer software. Nonformal…
A SYNOPTIC APPROACH FOR ASSESSING CUMULATIVE IMPACTS TO WETLANDS
The US Environmental Protection Agency's Wetlands Research Program has developed the synoptic approach as a proposed method for assessing cumulative impacts to wetlands by providing both a general and a comprehensive view of the environment. It can also be applied more broadly to...
Markus, Keith A
2016-01-01
Nesselroade and Molenaar presented the ideographic filter as a proposal for analyzing lawful regularities in behavioral research. The proposal highlights an inconsistency that poses a challenge for behavioral research more generally. One can distinguish a broadly Humean approach from a broadly non-Humean approach as they relate to variables and to causation. Nesselroade and Molenaar rejected a Humean approach to latent variables that characterizes them as nothing more than summaries of their manifest indicators. By contrast, they tacitly accepted a Humean approach to causes characterized as nothing more than summaries of their manifest causal effects. A non-Humean treatment of variables coupled with a Humean treatment of causation creates a theoretical tension within their proposal. For example, one can interpret the same model elements as simultaneously representing both variables and causes. Future refinement of the ideographic filter proposal to address this tension could follow any of a number of strategies.
Implementation Measurement for Evidence-Based Violence Prevention Programs in Communities.
Massetti, Greta M; Holland, Kristin M; Gorman-Smith, Deborah
2016-08-01
Increasing attention to the evaluation, dissemination, and implementation of evidence-based programs (EBPs) has led to significant advancements in the science of community-based violence prevention. One of the prevailing challenges in moving from science to community involves implementing EBPs and strategies with quality. The CDC-funded National Centers of Excellence in Youth Violence Prevention (YVPCs) partner with communities to implement a comprehensive community-based strategy to prevent violence and to evaluate that strategy for impact on community-wide rates of violence. As part of their implementation approach, YVPCs document implementation of and fidelity to the components of the comprehensive youth violence prevention strategy. We describe the strategies and methods used by the six YVPCs to assess implementation and to use implementation data to inform program improvement efforts. The information presented describes the approach and measurement strategies employed by each center and for each program implemented in the partner communities. YVPCs employ both established and innovative strategies for measurement and tracking of implementation across a broad range of programs, practices, and strategies. The work of the YVPCs highlights the need to use data to understand the relationship between implementation of EBPs and youth violence outcomes.
An FPGA-based instrumentation platform for use at deep cryogenic temperatures
DOE Office of Scientific and Technical Information (OSTI.GOV)
Conway Lamb, I. D.; Colless, J. I.; Hornibrook, J. M.
2016-01-15
We describe the operation of a cryogenic instrumentation platform incorporating commercially available field-programmable gate arrays (FPGAs). The functionality of the FPGAs at temperatures approaching 4 K enables signal routing, multiplexing, and complex digital signal processing in close proximity to cooled devices or detectors within the cryostat. The performance of the FPGAs in a cryogenic environment is evaluated, including clock speed, error rates, and power consumption. Although constructed for the purpose of controlling and reading out quantum computing devices with low latency, the instrument is generic enough to be of broad use in a range of cryogenic applications.
Collapse of triangular channels in a soft elastomer
NASA Astrophysics Data System (ADS)
Tepáyotl-Ramírez, Daniel; Lu, Tong; Park, Yong-Lae; Majidi, Carmel
2013-01-01
We extend classical solutions in contact mechanics to examine the collapse of channels in a soft elastomer. These channels have triangular cross-section and collapse when pressure is applied to the surrounding elastomer. Treating the walls of the channel as indenters that penetrate the channel base, we derive an algebraic mapping between pressure and cross-sectional area. These theoretical predictions are in strong agreement with results that we obtain through finite element analysis and experimental measurements. This is accomplished without data fitting and suggests that the theoretical approach may be generalized to a broad range of cross-sectional geometries in soft microfluidics.
Intravital imaging of a spheroid-based orthotopic model of melanoma in the mouse ear skin
Chan, Keefe T.; Jones, Stephen W.; Brighton, Hailey E.; Bo, Tao; Cochran, Shelly D.; Sharpless, Norman E.; Bear, James E.
2017-01-01
Multiphoton microscopy is a powerful tool that enables the visualization of fluorescently tagged tumor cells and their stromal interactions within tissues in vivo. We have developed an orthotopic model of implanting multicellular melanoma tumor spheroids into the dermis of the mouse ear skin without the requirement for invasive surgery. Here, we demonstrate the utility of this approach to observe the primary tumor, single cell actin dynamics, and tumor-associated vasculature. These methods can be broadly applied to investigate an array of biological questions regarding tumor cell behavior in vivo. PMID:28748125
Nuclear technology and the space exploration missions
NASA Technical Reports Server (NTRS)
Brandhorst, Henry W.; Sovie, Ronald J.
1990-01-01
The strategy for a major exploration initiative leading to permanent human presence beyond earth orbit is still being developed; however enough is known to begin defining the role of nuclear technologies. Three broad areas are discussed: low power (less than 10 kWe) rover/vehicle power systems; integrated, evolutionary base power systems (25 to 100 kW) and nuclear energy for electric propulsion (2 to 100 MWe); and direct thermal propulsion (1000s MW). A phased, evolutionary approach is described for both the moon and Mars, and the benefits of nuclear technologies relative to solar and their integration are described.
2010-03-23
foundation of our S&T portfolio by developing a broad base of scientific knowledge from which INP, FNC, and quick reaction efforts are generated...optimally tailoring experiences, in real-time, to current cognitive and physiological states of the learner. A unique human systems design approach is...efforts include modeling human responses to blast, ballistic, and blunt trauma, as well as modeling physical and cognitive effects of blast exposure and
Graphene-based nanomaterials for nanobiotechnology and biomedical applications.
Krishna, K Vijaya; Ménard-Moyon, Cécilia; Verma, Sandeep; Bianco, Alberto
2013-10-01
Graphene family nanomaterials are currently being extensively explored for applications in the field of nanotechnology. The unique intrinsic properties treasured in their simple molecular design and their ability to work in coherence with other existing nanomaterials make graphene family nanomaterials the most promising candidates for different types of applications. This review highlights the scope and utility of these multifaceted nanomaterials in nanobiotechnology and biomedicine. In a tandem approach, this review presents the smooth inclusion of these nanomaterials into existing designs for creating efficient working models at the nanoscale level as well as discussing their broad future possibilities.
Challenges Facing Global Health Networks: The NCD Alliance Experience
Dain, Katie
2018-01-01
Successful prevention and control of the epidemic of noncommunicable diseases (NCDs) cannot be achieved by the health sector alone: a wide range of organisations from multiple sectors and across government must also be involved. This requires a new, inclusive approach to advocacy and to coordinating, convening and catalysing action across civil society, best achieved by a broad-based network. This comment maps the experience of the NCD Alliance (NCDA) on to Shiffman’s challenges for global health networks – framing (problem definition and positioning), coalition-building and governance – and highlights some further areas overlooked in his analysis. PMID:29524960
Multi-country health surveys: are the analyses misleading?
Masood, Mohd; Reidpath, Daniel D
2014-05-01
The aim of this paper was to review the types of approaches currently utilized in the analysis of multi-country survey data, specifically focusing on design and modeling issues with a focus on analyses of significant multi-country surveys published in 2010. A systematic search strategy was used to identify the 10 multi-country surveys and the articles published from them in 2010. The surveys were selected to reflect diverse topics and foci; and provide an insight into analytic approaches across research themes. The search identified 159 articles appropriate for full text review and data extraction. The analyses adopted in the multi-country surveys can be broadly classified as: univariate/bivariate analyses, and multivariate/multivariable analyses. Multivariate/multivariable analyses may be further divided into design- and model-based analyses. Of the 159 articles reviewed, 129 articles used model-based analysis, 30 articles used design-based analyses. Similar patterns could be seen in all the individual surveys. While there is general agreement among survey statisticians that complex surveys are most appropriately analyzed using design-based analyses, most researchers continued to use the more common model-based approaches. Recent developments in design-based multi-level analysis may be one approach to include all the survey design characteristics. This is a relatively new area, however, and there remains statistical, as well as applied analytic research required. An important limitation of this study relates to the selection of the surveys used and the choice of year for the analysis, i.e., year 2010 only. There is, however, no strong reason to believe that analytic strategies have changed radically in the past few years, and 2010 provides a credible snapshot of current practice.
Hubbard, Rebecca A; Benjamin-Johnson, Rhondee; Onega, Tracy; Smith-Bindman, Rebecca; Zhu, Weiwei; Fenton, Joshua J
2015-01-15
Quality assessment is critical for healthcare reform, but data sources are lacking for measurement of many important healthcare outcomes. With over 49 million people covered by Medicare as of 2010, Medicare claims data offer a potentially valuable source that could be used in targeted health care quality improvement efforts. However, little is known about the operating characteristics of provider profiling methods using claims-based outcome measures that may estimate provider performance with error. Motivated by the example of screening mammography performance, we compared approaches to identifying providers failing to meet guideline targets using Medicare claims data. We used data from the Breast Cancer Surveillance Consortium and linked Medicare claims to compare claims-based and clinical estimates of cancer detection rate. We then demonstrated the performance of claim-based estimates across a broad range of operating characteristics using simulation studies. We found that identification of poor performing providers was extremely sensitive to algorithm specificity, with no approach identifying more than 65% of poor performing providers when claims-based measures had specificity of 0.995 or less. We conclude that claims have the potential to contribute important information on healthcare outcomes to quality improvement efforts. However, to achieve this potential, development of highly accurate claims-based outcome measures should remain a priority. Copyright © 2014 John Wiley & Sons, Ltd.
NASA Astrophysics Data System (ADS)
Trimarchi, Giancarlo; Zhang, Xiuwen; DeVries Vermeer, Michael J.; Cantwell, Jacqueline; Poeppelmeier, Kenneth R.; Zunger, Alex
2015-10-01
Theoretical sorting of stable and synthesizable "missing compounds" from those that are unstable is a crucial step in the discovery of previously unknown functional materials. This active research area often involves high-throughput (HT) examination of the total energy of a given compound in a list of candidate formal structure types (FSTs), searching for those with the lowest energy within that list. While it is well appreciated that local relaxation methods based on a fixed list of structure types can lead to inaccurate geometries, this approach is widely used in HT studies because it produces answers faster than global optimization methods (that vary lattice vectors and atomic positions without local restrictions). We find, however, a different failure mode of the HT protocol: specific crystallographic classes of formal structure types each correspond to a series of chemically distinct "daughter structure types" (DSTs) that have the same space group but possess totally different local bonding configurations, including coordination types. Failure to include such DSTs in the fixed list of examined candidate structures used in contemporary high-throughput approaches can lead to qualitative misidentification of the stable bonding pattern, not just quantitative inaccuracies. In this work, we (i) clarify the understanding of the general DST-FST relationship, thus improving current discovery HT approaches, (ii) illustrate this failure mode for RbCuS and RbCuSe (the latter being a yet unreported compound and is predicted here) by developing a synthesis method and accelerated crystal-structure determination, and (iii) apply the genetic-algorithm-based global space-group optimization (GSGO) approach which is not vulnerable to the failure mode of HT searches of fixed lists, demonstrating a correct identification of the stable DST. The broad impact of items (i)-(iii) lies in the demonstrated predictive ability of a more comprehensive search strategy than what is currently used—use HT calculations as the preliminary broad screening followed by unbiased GSGO of the final candidates.
Vaccines against malaria-still a long way to go.
Matuschewski, Kai
2017-08-01
Several species of Plasmodium cause a broad spectrum of human disease that range from nausea and fever to severe anemia, cerebral malaria, and multiorgan failure. In malaria-endemic countries, continuous exposure to Plasmodium sporozoite inoculations and subsequent blood infections elicit only partial and short-lived immunity, which gradually develops over many years of parasite exposure and multiple clinical episodes. The ambitious goal of malaria vaccinology over the past 70 years has been to develop an immunization strategy that mounts protection superior to naturally acquired immunity. Herein, three principal concepts in evidence-based malaria vaccine development are compared. Feasible leads are typically stand-alone subunit vaccine approaches that block Plasmodium parasite life cycle progression or parasite/host interactions, and they constitute the majority of candidates in preclinical research and early clinical testing. Integrated approaches incorporate malaria antigen(s) into licensed or emerging pediatric vaccine formulations. This strategy can complement the malaria control portfolio even if the antimalarial component is only partially effective and has led to the development of the only candidate vaccine to date, namely RTS,S-AS01. Experimental whole parasite vaccine approaches have been repeatedly shown to elicit sterile and lasting protection against identical parasite strains, but mass production, proof of broad protection against different parasite strains, and routes of vaccine delivery remain significant translational road blocks. Global access to an effective and affordable malaria vaccine will critically depend on innovative translational research that builds on a better molecular understanding of Plasmodium biology and host immunity. © 2017 Federation of European Biochemical Societies.