Control of oil spills in high speed currents : a technology assessment

DOT National Transportation Integrated Search

1999-05-01

A technology assessment has been conducted to analyze the threat of oil spills in fast currents. Technologies and methods for response were evaluated, and promising equipment and strategies were identified. Recommendations are made to pursue those me...

Candidate gene prioritization by network analysis of differential expression using machine learning approaches

PubMed Central

2010-01-01

Background Discovering novel disease genes is still challenging for diseases for which no prior knowledge - such as known disease genes or disease-related pathways - is available. Performing genetic studies frequently results in large lists of candidate genes of which only few can be followed up for further investigation. We have recently developed a computational method for constitutional genetic disorders that identifies the most promising candidate genes by replacing prior knowledge by experimental data of differential gene expression between affected and healthy individuals. To improve the performance of our prioritization strategy, we have extended our previous work by applying different machine learning approaches that identify promising candidate genes by determining whether a gene is surrounded by highly differentially expressed genes in a functional association or protein-protein interaction network. Results We have proposed three strategies scoring disease candidate genes relying on network-based machine learning approaches, such as kernel ridge regression, heat kernel, and Arnoldi kernel approximation. For comparison purposes, a local measure based on the expression of the direct neighbors is also computed. We have benchmarked these strategies on 40 publicly available knockout experiments in mice, and performance was assessed against results obtained using a standard procedure in genetics that ranks candidate genes based solely on their differential expression levels (Simple Expression Ranking). Our results showed that our four strategies could outperform this standard procedure and that the best results were obtained using the Heat Kernel Diffusion Ranking leading to an average ranking position of 8 out of 100 genes, an AUC value of 92.3% and an error reduction of 52.8% relative to the standard procedure approach which ranked the knockout gene on average at position 17 with an AUC value of 83.7%. Conclusion In this study we could identify promising candidate genes using network based machine learning approaches even if no knowledge is available about the disease or phenotype. PMID:20840752

Contingency Space Analysis: An Alternative Method for Identifying Contingent Relations from Observational Data

PubMed Central

Martens, Brian K; DiGennaro, Florence D; Reed, Derek D; Szczech, Frances M; Rosenthal, Blair D

2008-01-01

Descriptive assessment methods have been used in applied settings to identify consequences for problem behavior, thereby aiding in the design of effective treatment programs. Consensus has not been reached, however, regarding the types of data or analytic strategies that are most useful for describing behavior–consequence relations. One promising approach involves the analysis of conditional probabilities from sequential recordings of behavior and events that follow its occurrence. In this paper we review several strategies for identifying contingent relations from conditional probabilities, and propose an alternative strategy known as a contingency space analysis (CSA). Step-by-step procedures for conducting and interpreting a CSA using sample data are presented, followed by discussion of the potential use of a CSA for conducting descriptive assessments, informing intervention design, and evaluating changes in reinforcement contingencies following treatment. PMID:18468280

Analysis of Propagation Plans in NSF-Funded Education Development Projects

ERIC Educational Resources Information Center

Stanford, Courtney; Cole, Renee; Froyd, Jeff; Henderson, Charles; Friedrichsen, Debra; Khatri, Raina

2017-01-01

Increasing adoption and adaptation of promising instructional strategies and materials has been identified as a critical component needed to improve science, technology, engineering, and mathematics (STEM) education. This paper examines typical propagation practices and resulting outcomes of proposals written by developers of educational…

Variations on a Theme: Colleague Consultant Networks.

ERIC Educational Resources Information Center

Garth, Russell; Rehnke, Mary Ann

1991-01-01

Although the use of formal consulting networks based in higher education's professional associations has declined somewhat, other, less formal strategies for identifying colleague consultants show promise. Flexible networks are being built on the principle of cooperative self-help, without centralized facilitation, to enable colleges to find…

Supporting Implementation of Evidence-Based Practices through Practice-Based Coaching

ERIC Educational Resources Information Center

Snyder, Patricia A; Hemmeter, Mary Louise; Fox, Lise

2015-01-01

In active implementation science frameworks, coaching has been described as an important competency "driver" to ensure evidence-based practices are implemented as intended. Empirical evidence also has identified coaching as a promising job-embedded professional development strategy to support implementation of quality teaching practices.…

Engaging Communities in Identifying Local Strategies for Expanding Integrated Employment During and After High School.

PubMed

Carter, Erik W; Blustein, Carly L; Bumble, Jennifer L; Harvey, Sarah; Henderson, Lynnette M; McMillan, Elise D

2016-09-01

Amidst decades of attention directed toward improving employment outcomes for people with intellectual and developmental disabilities (IDD), few efforts have been made to engage communities in identifying local solutions for expanding integrated employment opportunities. We examined the implementation and outcomes of "community conversation" events held in 6 geographically and economically diverse locales. Each event used an asset-based dialogue approach called the World Café ( Brown & Isaacs, 2005 ) to solicit ideas from a broad cross-section of community members on improving integrated employment that reflect local priorities and possibilities. Six key themes encapsulated the 1,556 strategies generated by the almost 400 attendees. Although considerable consistency was found among the categories of strategies raised across events, the manner in which those individual strategies would be implemented locally reflected the unique accent of each community. Attendees also viewed these events as promising and productive pathways for identifying next steps for their community. We offer recommendations for community-level intervention efforts and suggest directions for future research.

Which uncertainty? Using expert elicitation and expected value of information to design an adaptive program

USGS Publications Warehouse

Runge, Michael C.; Converse, Sarah J.; Lyons, James E.

2011-01-01

Natural resource management is plagued with uncertainty of many kinds, but not all uncertainties are equally important to resolve. The promise of adaptive management is that learning in the short-term will improve management in the long-term; that promise is best kept if the focus of learning is on those uncertainties that most impede achievement of management objectives. In this context, an existing tool of decision analysis, the expected value of perfect information (EVPI), is particularly valuable in identifying the most important uncertainties. Expert elicitation can be used to develop preliminary predictions of management response under a series of hypotheses, as well as prior weights for those hypotheses, and the EVPI can be used to determine how much management could improve if uncertainty was resolved. These methods were applied to management of whooping cranes (Grus americana), an endangered migratory bird that is being reintroduced in several places in North America. The Eastern Migratory Population of whooping cranes had exhibited almost no successful reproduction through 2009. Several dozen hypotheses can be advanced to explain this failure, and many of them lead to very different management responses. An expert panel articulated the hypotheses, provided prior weights for them, developed potential management strategies, and made predictions about the response of the population to each strategy under each hypothesis. Multi-criteria decision analysis identified a preferred strategy in the face of uncertainty, and analysis of the expected value of information identified how informative each strategy could be. These results provide the foundation for design of an adaptive management program.

Branding strategies discussed by the experts. Trends that will shape strategy in 1998.

PubMed

Windhorst, C E

1998-02-01

This month the focus is on branding. The Alliance Advisory Council's discussion of this topic, led by Joel English (a senior vice president with BVK/McDonald, Milwaukee, WI), identifies the key issues on branding as: 1) the debate between the local and regional nature of healthcare delivery, and the need to provide customers with the trust and security of a larger entity behind the individual provider; 2) the challenge of identifying and agreeing on a consistent message for all parts of the system; and 3) the difficulty of keeping the promise implied by a brand across these many components.

Rational design of new electrolyte materials for electrochemical double layer capacitors

NASA Astrophysics Data System (ADS)

Schütter, Christoph; Husch, Tamara; Viswanathan, Venkatasubramanian; Passerini, Stefano; Balducci, Andrea; Korth, Martin

2016-09-01

The development of new electrolytes is a centerpiece of many strategies to improve electrochemical double layer capacitor (EDLC) devices. We present here a computational screening-based rational design approach to find new electrolyte materials. As an example application, the known chemical space of almost 70 million compounds is investigated in search of electrochemically more stable solvents. Cyano esters are identified as especially promising new compound class. Theoretical predictions are validated with subsequent experimental studies on a selected case. These studies show that based on theoretical predictions only, a previously untested, but very well performing compound class was identified. We thus find that our rational design strategy is indeed able to successfully identify completely new materials with substantially improved properties.

High resolution techno-ecological modeling of a bioenergy landscape to identify climate mitigation opportunities in cellulosic ethanol production

USDA-ARS?s Scientific Manuscript database

Meeting current biofuel mandates or creating future carbon-negative biopower systems requires feedstocks be sourced in sufficient quantities at low cost and with minimal environmental impact. Cultivating perennial grasses on low-quality lands is a promising feedstock supply strategy minimizing on-...

Brain-penetrating 2-aminobenzimidazole H(1)-antihistamines for the treatment of insomnia.

PubMed

Coon, Timothy; Moree, Wilna J; Li, Binfeng; Yu, Jinghua; Zamani-Kord, Said; Malany, Siobhan; Santos, Mark A; Hernandez, Lisa M; Petroski, Robert E; Sun, Aixia; Wen, Jenny; Sullivan, Sue; Haelewyn, Jason; Hedrick, Michael; Hoare, Samuel J; Bradbury, Margaret J; Crowe, Paul D; Beaton, Graham

2009-08-01

The benzimidazole core of the selective non-brain-penetrating H(1)-antihistamine mizolastine was used to identify a series of brain-penetrating H(1)-antihistamines for the potential treatment of insomnia. Using cassette PK studies, brain-penetrating H(1)-antihistamines were identified and in vivo efficacy was demonstrated in a rat EEG/EMG model. Further optimization focused on strategies to attenuate an identified hERG liability, leading to the discovery of 4i with a promising in vitro profile.

Documenting Instructional Practices in Large Introductory STEM Lecture Courses

NASA Astrophysics Data System (ADS)

Vu, Viet Quoc

STEM education reform in higher education is framed around the need to improve student learning outcomes, increase student retention, and increase the number of underrepresented minorities and female students in STEM fields, all of which would ultimately contribute to America's competitiveness and prosperity. To achieve these goals, education reformers call for an increase in the adoption of research-based "promising practices" in classrooms. Despite efforts to increase the adoption of more promising practices in classrooms, postsecondary instructors are still likely to lecture and use traditional teaching approaches. To shed light on this adoption dilemma, a mix-methods study was conducted. First, instructional practices in large introductory STEM courses were identified, followed by an analysis of factors that inhibit or contribute to the use of promising practices. Data were obtained from classroom observations (N = 259) of large gateway courses across STEM departments and from instructor interviews (N = 67). Results show that instructors are already aware of promising practices and that change strategies could move from focusing on the development and dissemination of promising practices to focusing on improving adoption rates. Teaching-track instructors such as lecturers with potential for security of employment (LPSOE) and lecturers with security of employment (LSOE) have adopted promising practices more than other instructors. Interview data show that LPSOEs are also effective at disseminating promising practices to their peers, but opinion leaders (influential faculty in a department) are necessary to promote adoption of promising practices by higher ranking instructors. However, hiring more LPSOEs or opinion leaders will not be enough to shift instructional practices. Variations in the adoption of promising practices by instructors and across departments show that any reform strategy needs to be systematic and take into consideration how information is shared through communication channels, the adoption decision-making process by potential adopters, and the contextual barriers and drivers of adoption. Additionally, the strategy should be designed with multiple stages, with each stage given time for changes to have an effect. Taking a one-size fits all approach to STEM education reform will not work and may only perpetuate the cycle of non-adoption and continued use of teacher-centered instructional practices.

Establishing and Sustaining Networked Improvement Communities: Lessons from Michigan and Minnesota. REL 2017-264

ERIC Educational Resources Information Center

Proger, Amy R.; Bhatt, Monica P.; Cirks, Victoria; Gurke, Deb

2017-01-01

There is growing interest in the ability of improvement science--the systematic study of improvement strategies to identify promising practices for addressing issues in complex systems (Improvement Science Research Network, 2016)--to spur innovation and address complex problems. In education this methodology is often implemented through…

Identifying/Quantifying Environmental Trade-offs Inherent in GHG Reduction Strategies for Coal-Fired Power. Environmental Science and Technology

EPA Science Inventory

Improvements to coal power plant technology and the co-fired combustion of biomass promise direct greenhouse gas (GHG) reductions for existing coal-fired power plants. Questions remain as to what the reduction potentials are from a life cycle perspective and if it will result in ...

Healthcare Providers' Treatment of College Smokers

ERIC Educational Resources Information Center

Koontz, Jennifer Scott; Harris, Kari Jo; Okuyemi, Kolawole S.; Mosier, Michael C.; Grobe, James; Nazir, Niaman; Ahluwalia, Jasjit S.

2004-01-01

About 28% of college students smoke tobacco, and many will continue smoking into adulthood. Although little is known about how to help college students quit smoking. I promising strategy is healthcare providers' advice. To estimate their lifetime receipt of brief advice and to identify characteristics that predict who may receive that advice, 348…

The Place of Autonomy in School Community: Taking a Closer Look at Teacher Collaboration

ERIC Educational Resources Information Center

Gates, Gordon S.; Watkins, Millie

2010-01-01

Teachers hold the key to school reform. Professional learning communities--as well as other related strategies, including collaborative and distributive models of leadership--offer much that is promising. Yet, weaknesses documented in research require attention. We conducted a study of teachers in two elementary schools identified as exemplary…

Review and Analysis of Curricula for Occupations in Food Processing and Distribution. Information Series No. 32.

ERIC Educational Resources Information Center

Lewis, Wiley B.

A review and analysis of Educational Resources Information Center (ERIC) publications and non-ERIC publications was made to assess availability and identify major findings, promising developments, strategies, and methodological strengths and weaknesses which exist in curricula designed for preparing food industry workers. Project national figures…

Review and Analysis of Curricula For Occupations in Public Services. Information Series No. 29.

ERIC Educational Resources Information Center

Lewis, Wiley B.

To identify major findings, promising developments, strategies, and methodological strengths and weaknesses which exist in curricula designed for training paraprofessional public service workers in the fields of education, social work, law enforcement, and fire fighting, a review and analysis was made of Educational Resources Information Center…

Visual Supports for the Learning Disabled: A Handbook for Educators

ERIC Educational Resources Information Center

Sells, Leighan

2013-01-01

A large percent of the population is affected by learning disabilities, which significantly impacts individuals and families. Much research has been done to identify effective ways to best help the students with learning disabilities. One of the more promising strategies is the use of visual supports to enhance these students' understanding…

PROspective Multicenter Imaging Study for Evaluation of Chest Pain: Rationale and Design of the PROMISE Trial

PubMed Central

Douglas, Pamela S.; Hoffmann, Udo; Lee, Kerry L.; Mark, Daniel B.; Al-Khalidi, Hussein R.; Anstrom, Kevin; Dolor, Rowena J.; Kosinski, Andrzej; Krucoff, Mitchell W.; Mudrick, Daniel W.; Patel, Manesh R.; Picard, Michael H.; Udelson, James E.; Velazquez, Eric J.; Cooper, Lawton

2014-01-01

Background Suspected coronary artery disease (CAD) is one of the most common, potentially life threatening diagnostic problems clinicians encounter. However, no large outcome-based randomized trials have been performed to guide the selection of diagnostic strategies for these patients. Methods The PROMISE study is a prospective, randomized trial comparing the effectiveness of two initial diagnostic strategies in patients with symptoms suspicious for CAD. Patients are randomized to either: 1) functional testing (exercise electrocardiogram, stress nuclear imaging, or stress echocardiogram); or 2) anatomic testing with >=64 slice multidetector coronary computed tomographic angiography. Tests are interpreted locally in real time by subspecialty certified physicians and all subsequent care decisions are made by the clinical care team. Sites are provided results of central core lab quality and completeness assessment. All subjects are followed for ≥1 year. The primary end-point is the time to occurrence of the composite of death, myocardial infarction, major procedural complications (stroke, major bleeding, anaphylaxis and renal failure) or hospitalization for unstable angina. Results Over 10,000 symptomatic subjects were randomized in 3.2 years at 193 US and Canadian cardiology, radiology, primary care, urgent care and anesthesiology sites. Conclusion Multi-specialty community practice enrollment into a large pragmatic trial of diagnostic testing strategies is both feasible and efficient. PROMISE will compare the clinical effectiveness of an initial strategy of functional testing against an initial strategy of anatomic testing in symptomatic patients with suspected CAD. Quality of life, resource use, cost effectiveness and radiation exposure will be assessed. Clinical trials.gov identifier NCT01174550 PMID:24890527

Identifying Links Between Sexual Violence and Youth Violence Perpetration: New Opportunities for Sexual Violence Prevention

PubMed Central

DeGue, Sarah; Massetti, Greta M.; Holt, Melissa K.; Tharp, Andra Teten; Valle, Linda Anne; Matjasko, Jennifer L.; Lippy, Caroline

2018-01-01

Objective One promising opportunity for advancing sexual violence (SV) research and identifying new avenues for prevention involves examining other forms of violence that may share risk factors with SV. Youth violence (YV) is ideal for consideration given evidence of overlap in SV and YV risk factors, a large set of established YV risk factors across the social ecology, and the number of evidence-based YV prevention strategies available. The current paper identifies shared and unique risk factors for SV and YV and highlights evidence-based YV prevention strategies that impact these shared risk factors. Conclusions Researchers and program developers should consider adapting and evaluating evidence-based YV prevention strategies to prevent SV. Modifying these programs to address SV’s unique risk factors may maximize their potential effectiveness. In addition, expanding SV research at the outer levels of the social ecology is critical to developing community-level prevention strategies. The YV literature suggests several potential risk factors at these levels in need of research for SV, including school connectedness, social disorganization, and availability of alcohol and drugs. Using the YV literature as a starting point for expanding SV research leverages prior investments in YV research, may help identify new SV prevention strategies at a limited cost, and moves the field more quickly toward implementation of cost-effective, multidomain violence prevention strategies in communities. PMID:29644117

Rapid identification of herbal compounds derived metabolites using zebrafish larvae as the biotransformation system.

PubMed

Wang, Chen; Yin, Ying-Hao; Wei, Ying-Jie; Shi, Zi-Qi; Liu, Jian-Qun; Liu, Li-Fang; Xin, Gui-Zhong

2017-09-15

Metabolites derived from herbal compounds are becoming promising sources for discovering new drugs. However, the rapid identification of metabolites from biological matrixes is limited by massive endogenous interference and low abundance of metabolites. Thus, by using zebrafish larvae as the biotransformation system, we herein proposed and validated an integrated strategy for rapid identification of metabolites derived from herbal compounds. Two pivotal steps involved in this strategy are to differentiate metabolites from herbal compounds and match metabolites with their parent compounds. The differentiation step was achieved by cross orthogonal partial least-squares discriminant analysis. Automatic matching analysis was performed on R Project based on a self-developed program, of which the number of matched ionic clusters and its corresponding percentage between metabolite and parent compound were taken into account to assess their similarity. Using this strategy, 46 metabolites screened from incubation water samples of zebrafish treated with total Epimedium flavonoids (EFs) could be matched with their corresponding parent compounds, 37 of them were identified and validated by the known metabolic pathways and fragmentation patterns. Finally, 75% of the identified EFs metabolites were successfully detected in urine samples of rats treated with EFs. These experimental results indicate that the proposed strategy using zebrafish larvae as the biotransformation system will facilitate the rapid identification of metabolites derived from herbal compounds, which shows promising perspectives in providing additional resources for pharmaceutical developments from natural products. Copyright © 2017 Elsevier B.V. All rights reserved.

Promising New Teacher Support Strategies and Their Costs.

ERIC Educational Resources Information Center

Dianda, Marcella R.; Quartz, Karen Hunter

1995-01-01

Describes several promising new teacher support strategies implemented by California universities and their district partners as part of the California New Teacher Project, noting resources expended to implement each strategy. The strategies are framed according to their programmatic and economic dimensions. Strategies that make the most sense…

Cyanobacterial biofuels: new insights and strain design strategies revealed by computational modeling.

PubMed

Erdrich, Philipp; Knoop, Henning; Steuer, Ralf; Klamt, Steffen

2014-09-19

Cyanobacteria are increasingly recognized as promising cell factories for the production of renewable biofuels and chemical feedstocks from sunlight, CO2, and water. However, most biotechnological applications of these organisms are still characterized by low yields. Increasing the production performance of cyanobacteria remains therefore a crucial step. In this work we use a stoichiometric network model of Synechocystis sp. PCC 6803 in combination with CASOP and minimal cut set analysis to systematically identify and characterize suitable strain design strategies for biofuel synthesis, specifically for ethanol and isobutanol. As a key result, improving upon other works, we demonstrate that higher-order knockout strategies exist in the model that lead to coupling of growth with high-yield biofuel synthesis under phototrophic conditions. Enumerating all potential knockout strategies (cut sets) reveals a unifying principle behind the identified strain designs, namely to reduce the ratio of ATP to NADPH produced by the photosynthetic electron transport chain. Accordingly, suitable knockout strategies seek to block cyclic and other alternate electron flows, such that ATP and NADPH are exclusively synthesized via the linear electron flow whose ATP/NADPH ratio is below that required for biomass synthesis. The products of interest are then utilized by the cell as sinks for reduction equivalents in excess. Importantly, the calculated intervention strategies do not rely on the assumption of optimal growth and they ensure that maintenance metabolism in the absence of light remains feasible. Our analyses furthermore suggest that a moderately increased ATP turnover, realized, for example, by ATP futile cycles or other ATP wasting mechanisms, represents a promising target to achieve increased biofuel yields. Our study reveals key principles of rational metabolic engineering strategies in cyanobacteria towards biofuel production. The results clearly show that achieving obligatory coupling of growth and product synthesis in photosynthetic bacteria requires fundamentally different intervention strategies compared to heterotrophic organisms.

Evaluating Testing Strategies for Identifying Youths With HIV Infection and Linking Youths to Biomedical and Other Prevention Services

PubMed Central

Boyer, Cherrie B.; Chiaramonte, Danielle; Lindeman, Peter; Chutuape, Kate; Cooper-Walker, Bendu; Kapogiannis, Bill G.; Wilson, Craig M.; Fortenberry, J. Dennis

2017-01-01

Importance Most human immunodeficiency virus (HIV)–infected youths are unaware of their serostatus (approximately 60%) and therefore not linked to HIV medical or prevention services. The need to identify promising and scalable approaches to promote uptake of HIV testing among youths at risk is critical. Objective To evaluate a multisite HIV testing program designed to encourage localized HIV testing programs focused on self-identified sexual minority males and to link youths to appropriate prevention services after receipt of their test results. Design, Setting, and Participants Testing strategies were evaluated using an observational design during a 9-month period (June 1, 2015, through February 28, 2016). Testing strategies were implemented by 12 adolescent medicine HIV primary care programs and included targeted testing, universal testing, or a combination. Data were collected from local youth at high risk of HIV infection and, specifically, sexual minority males of color. Main Outcomes and Measures Proportion of sexual minority males and sexual minority males of color tested, proportion of previously undiagnosed HIV-positive youths identified, and rates of linkage to prevention services. Results A total of 3301 youths underwent HIV testing. Overall, 35 (3.6%) of those who underwent universal testing in primary care clinical settings, such as emergency departments and community health centers, were sexual minority males (35 [3.6%] were males of color) compared with 236 (46.7%) (201 [39.8%] were males of color) who were tested through targeted testing and 693 (37.8%) (503 [27.4%] were males of color) through combination efforts. Identification of new HIV-positive cases varied by strategy: 1 (0.1%) via universal testing, 39 (2.1%) through combination testing, and 16 (3.2%) through targeted testing. However, when targeted tests were separated from universal testing results for sites using a combined strategy, the rate of newly identified HIV-positive cases identified through universal testing decreased to 1 (0.1%). Rates of new HIV-positive cases identified through targeted testing increased to 49 (6.3%). Youths who tested through targeted testing (416 [85.1%]) were more likely to link successfully to local HIV prevention services, including preexposure prophylaxis, compared with those who underwent universal testing (328 [34.1%]). Conclusions and Relevance The findings suggest that community-based targeted approaches to HIV testing are more effective than universal screening for reaching young sexual minority males (especially males of color), identifying previously undiagnosed HIV-positive youths, and linking HIV-negative youths to relevant prevention services. Targeted, community-based HIV testing strategies hold promise as a scalable and effective means to identify high-risk youths who are unaware of their HIV status. PMID:28418524

Effects of GO FASTER on Morpheme Definition Fluency for High School Students with High-Incidence Disabilities

ERIC Educational Resources Information Center

Fishley, Katelyn M.; Konrad, Moira; Hessler, Terri; Keesey, Susan

2012-01-01

Although vocabulary plays an important role in literacy and content instruction, there is a paucity of research identifying effective methods for teaching vocabulary. One promising strategy is morphemic analysis, which involves breaking words into morphemes, the smallest meaningful parts of words, and teaching students the meanings of those parts.…

Self-Management of On-Task Homework Behavior: A Promising Strategy for Adolescents with Attention and Behavior Problems

ERIC Educational Resources Information Center

Axelrod, Michael I.; Zhe, Elizabeth J.; Haugen, Kimberly A.; Klein, Jean A.

2009-01-01

Students with attention and behavior problems oftentimes experience difficulty finishing academic work. On-task behavior is frequently cited as a primary reason for students' failure to complete homework assignments. Researchers have identified self-monitoring and self-management of on-task behavior as effective tools for improving homework…

Strategic questions for consumer-based health communications.

PubMed Central

Sutton, S M; Balch, G I; Lefebvre, R C

1995-01-01

Using the consumer-oriented approach of social and commercial marketers, this article presents a process for crafting messages designed to improve people's health behaviors. The process, termed consumer-based health communications (CHC), transforms scientific recommendations into message strategies that are relevant to the consumer. The core of CHC is consumer research conducted to understand the consumer's reality, and thereby allowing six strategic questions to be answered. The immediate result of the CHC process is a strategy statement--a few pages that lay out who the target consumer is, what action should be taken, what to promise and how to make the promise credible, how and when to reach him or her, and what image to convey. The strategy statement then guides the execution of all communication efforts, be they public relations, mass media, direct marketing, media advocacy, or interpersonal influence. It identifies the most important "levers" for contact with the consumer. Everyone from creative specialists through management and program personnel can use the strategy statement as a touchstone to guide and judge the effectiveness of their efforts. The article provides a step by step illustration of the CHC process using the 5 A Day campaign as an example. PMID:8570827

Strategic questions for consumer-based health communications.

PubMed

Sutton, S M; Balch, G I; Lefebvre, R C

1995-01-01

Using the consumer-oriented approach of social and commercial marketers, this article presents a process for crafting messages designed to improve people's health behaviors. The process, termed consumer-based health communications (CHC), transforms scientific recommendations into message strategies that are relevant to the consumer. The core of CHC is consumer research conducted to understand the consumer's reality, and thereby allowing six strategic questions to be answered. The immediate result of the CHC process is a strategy statement--a few pages that lay out who the target consumer is, what action should be taken, what to promise and how to make the promise credible, how and when to reach him or her, and what image to convey. The strategy statement then guides the execution of all communication efforts, be they public relations, mass media, direct marketing, media advocacy, or interpersonal influence. It identifies the most important "levers" for contact with the consumer. Everyone from creative specialists through management and program personnel can use the strategy statement as a touchstone to guide and judge the effectiveness of their efforts. The article provides a step by step illustration of the CHC process using the 5 A Day campaign as an example.

Towards repurposing the yeast peroxisome for compartmentalizing heterologous metabolic pathways

DOE PAGES

DeLoache, William C.; Russ, Zachary N.; Dueber, John E.

2016-03-30

Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk and improving pathway efficiency, but improved tools and design rules are needed to make this strategy available to more engineered pathways. Here we focus on the Saccharomyces cerevisiae peroxisome and develop a sensitive high-throughput assay for peroxisomal cargo import. We identify an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly sequestering non-native cargo proteins. Additionally, we perform the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay. Finally, we apply these new insights to compartmentalize a two-enzymemore » pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titre. Lastly, this work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.« less

Towards repurposing the yeast peroxisome for compartmentalizing heterologous metabolic pathways

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

DeLoache, William C.; Russ, Zachary N.; Dueber, John E.

Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk and improving pathway efficiency, but improved tools and design rules are needed to make this strategy available to more engineered pathways. Here we focus on the Saccharomyces cerevisiae peroxisome and develop a sensitive high-throughput assay for peroxisomal cargo import. We identify an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly sequestering non-native cargo proteins. Additionally, we perform the first systematic in vivo measurements of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay. Finally, we apply these new insights to compartmentalize a two-enzymemore » pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titre. Lastly, this work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.« less

Chemical Approaches to Control Gene Expression

PubMed Central

Gottesfeld, Joel M.; Turner, James M.; Dervan, Peter B.

2000-01-01

A current goal in molecular medicine is the development of new strategies to interfere with gene expression in living cells in the hope that novel therapies for human disease will result from these efforts. This review focuses on small-molecule or chemical approaches to manipulate gene expression by modulating either transcription of messenger RNA-coding genes or protein translation. The molecules under study include natural products, designed ligands, and compounds identified through functional screens of combinatorial libraries. The cellular targets for these molecules include DNA, messenger RNA, and the protein components of the transcription, RNA processing, and translational machinery. Studies with model systems have shown promise in the inhibition of both cellular and viral gene transcription and mRNA utilization. Moreover, strategies for both repression and activation of gene transcription have been described. These studies offer promise for treatment of diseases of pathogenic (viral, bacterial, etc.) and cellular origin (cancer, genetic diseases, etc.). PMID:11097426

T7 Phage Display Library a Promising Strategy to Detect Tuberculosis Specific Biomarkers.

PubMed

Talwar, Harvinder; Talreja, Jaya; Samavati, Lobelia

2016-06-01

One-third of the world's population is infected with tuberculosis, only 10% will develop active disease and the remaining 90% is considered to have latent TB (LTB). While active TB is contagious and can be lethal, the LTB can evolve to active TB. The diagnosis of TB can be challenging, especially in the early stages, due to the variability in presentation and nonspecific signs and symptoms. Currently, we have limited tools available to diagnose active TB, predict treatment efficacy and cure of active tuberculosis, the reactivation of latent tuberculosis infection, and the induction of protective immune responses through vaccination. Therefore, the identification of robust and accurate tuberculosis-specific biomarkers is crucial for the successful eradication of TB. In this commentary, we summarized the available methods for diagnosis and differentiation of active TB from LTB and their limitations. Additionally, we present a novel peptide microarray platform as promising strategy to identify TB biomarkers.

Strategies to identify and reduce opioid misuse among patients with gastrointestinal disorders: A systematic scoping review

PubMed Central

Balbale, Salva N.; Trivedi, Itishree; O’Dwyer, Linda C.; McHugh, Megan C.; Evans, Charlesnika T.; Jordan, Neil; Keefer, Laurie A.

2018-01-01

Background Scoping reviews are preliminary assessments intended to characterize the extent and nature of emerging research evidence, identify literature gaps, and offer directions for future research. We conducted a systematic scoping review to describe published scientific literature on strategies to identify and reduce opioid misuse among patients with gastrointestinal (GI) symptoms and disorders. Methods We performed structured keyword searches to identify manuscripts published through June 2016 in the PubMed MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science databases to extract original research articles that described health care practices, tools or interventions to identify and reduce opioid misuse among GI patients. The Chronic Care Model (CCM) was used to classify the strategies presented. Results Twelve articles met the inclusion criteria. A majority of studies used quasi-experimental or retrospective cohort study designs. Most studies addressed the CCM’s clinical information systems element. Seven studies involved identification of opioid misuse through prescription drug monitoring and opioid misuse screening tools. Four studies discussed reductions in opioid use by harnessing drug monitoring data and individual care plans, and implementing self-management and opioid detoxification interventions. One study described drug monitoring and an audit-and-feedback intervention to both identify and reduce opioid misuse. Greatest reductions in opioid misuse were observed when drug monitoring, self-management, or audit-and-feedback interventions were used. Conclusions Prescription drug monitoring and self-management interventions may be promising strategies to identify and reduce opioid misuse in gastrointestinal care. Rigorous, empirical research is needed to evaluate the longer-term impact of these strategies. PMID:28780607

Strategies to Identify and Reduce Opioid Misuse Among Patients with Gastrointestinal Disorders: A Systematic Scoping Review.

PubMed

Balbale, Salva N; Trivedi, Itishree; O'Dwyer, Linda C; McHugh, Megan C; Evans, Charlesnika T; Jordan, Neil; Keefer, Laurie A

2017-10-01

Scoping reviews are preliminary assessments intended to characterize the extent and nature of emerging research evidence, identify literature gaps, and offer directions for future research. We conducted a systematic scoping review to describe published scientific literature on strategies to identify and reduce opioid misuse among patients with gastrointestinal (GI) symptoms and disorders. We performed structured keyword searches to identify manuscripts published through June 2016 in the PubMed MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science databases to extract original research articles that described healthcare practices, tools, or interventions to identify and reduce opioid misuse among GI patients. The Chronic Care Model (CCM) was used to classify the strategies presented. Twelve articles met the inclusion criteria. A majority of studies used quasi-experimental or retrospective cohort study designs. Most studies addressed the CCM's clinical information systems element. Seven studies involved identification of opioid misuse through prescription drug monitoring and opioid misuse screening tools. Four studies discussed reductions in opioid use by harnessing drug monitoring data and individual care plans, and implementing self-management and opioid detoxification interventions. One study described drug monitoring and an audit-and-feedback intervention to both identify and reduce opioid misuse. Greatest reductions in opioid misuse were observed when drug monitoring, self-management, or audit-and-feedback interventions were used. Prescription drug monitoring and self-management interventions may be promising strategies to identify and reduce opioid misuse in GI care. Rigorous, empirical research is needed to evaluate the longer-term impact of these strategies.

High-throughput identification of antigen-specific TCRs by TCR gene capture.

PubMed

Linnemann, Carsten; Heemskerk, Bianca; Kvistborg, Pia; Kluin, Roelof J C; Bolotin, Dmitriy A; Chen, Xiaojing; Bresser, Kaspar; Nieuwland, Marja; Schotte, Remko; Michels, Samira; Gomez-Eerland, Raquel; Jahn, Lorenz; Hombrink, Pleun; Legrand, Nicolas; Shu, Chengyi Jenny; Mamedov, Ilgar Z; Velds, Arno; Blank, Christian U; Haanen, John B A G; Turchaninova, Maria A; Kerkhoven, Ron M; Spits, Hergen; Hadrup, Sine Reker; Heemskerk, Mirjam H M; Blankenstein, Thomas; Chudakov, Dmitriy M; Bendle, Gavin M; Schumacher, Ton N M

2013-11-01

The transfer of T cell receptor (TCR) genes into patient T cells is a promising approach for the treatment of both viral infections and cancer. Although efficient methods exist to identify antibodies for the treatment of these diseases, comparable strategies to identify TCRs have been lacking. We have developed a high-throughput DNA-based strategy to identify TCR sequences by the capture and sequencing of genomic DNA fragments encoding the TCR genes. We establish the value of this approach by assembling a large library of cancer germline tumor antigen-reactive TCRs. Furthermore, by exploiting the quantitative nature of TCR gene capture, we show the feasibility of identifying antigen-specific TCRs in oligoclonal T cell populations from either human material or TCR-humanized mice. Finally, we demonstrate the ability to identify tumor-reactive TCRs within intratumoral T cell subsets without knowledge of antigen specificities, which may be the first step toward the development of autologous TCR gene therapy to target patient-specific neoantigens in human cancer.

Capturing species-level drought responses in a temperate deciduous forest using ratios of photochemical reflectance indices between sunlit and shaded canopies

Treesearch

Taehee Hwang; Hamed Gholizadeh; Daniel A. Sims; Kimberly A. Novick; Edward R. Brzostek; Richard P. Phillips; Daniel T. Roman; Scott M. Robeson; Abdullah F. Rahman

2017-01-01

To classify trees along a spectrum of isohydric to anisohydric behavior is a promising new framework for identifying tree species' sensitivities to drought stress, directly related to the vulnerability of carbon uptake of terrestrial ecosystems with increased hydroclimate variability. Trees with isohydric strategies regulate stomatal conductance to maintain...

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

None, None

As part of the U.S. Navy's overall energy strategy, the National Renewable Energy Laboratory (NREL) partnered with the Naval Facilities Engineering Command (NAVFAC) to demonstrate market-ready energy efficiency measures, renewable energy generation, and energy systems integration. One such technology - retrofitting rooftop air-conditioning units with an advanced rooftop control system - was identified as a promising source for reducing energy use and costs, and can contribute to increasing energy security.

The power and promise of applying genomics to honey bee health.

PubMed

Grozinger, Christina M; Robinson, Gene E

2015-08-01

New genomic tools and resources are now being used to both understand honey bee health and develop tools to better manage it. Here, we describe the use of genomic approaches to identify and characterize bee parasites and pathogens, examine interactions among these parasites and pathogens, between them and their bee hosts, and to identify genetic markers for improved breeding of more resilient bee stocks. We also discuss several new genomic techniques that can be used to more efficiently study, monitor and improve bee health. In the case of using RNAi-based technologies to mitigate diseases in bee populations, we highlight advantages, disadvantages and strategies to reduce risk. The increased use of genomic analytical tools and manipulative technologies has already led to significant advances, and holds great promise for improvements in the health of honey bees and other critical pollinator species.

Comparative evaluation of electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) and high-pH reversed phase (Hp-RP) chromatography in profiling of rat kidney proteome.

PubMed

Hao, Piliang; Ren, Yan; Dutta, Bamaprasad; Sze, Siu Kwan

2013-04-26

ERLIC and high-pH RP (Hp-RP) have been reported to be promising alternatives to strong cation exchange (SCX) in proteome fractionation. Here we compared the performance of ERLIC, concatenated ERLIC and concatenated Hp-RP in proteome profiling. The protein identification is comparable in these three strategies, but significantly more unique peptides are identified by the two concatenation methods, resulting in a significant increase of the average protein sequence coverage. The pooling of fractions from spaced intervals results in more uniform distribution of peptides in each fraction compared with the chromatogram-based pooling of adjacent fractions. ERLIC fractionates peptides according to their pI and GRAVY values. These properties remains but becomes less remarkable in concatenated ERLIC. In contrast, the average pI and GRAVY values of the peptides are comparable in each fraction in concatenated Hp-RP. ERLIC performs the best in identifying peptides with pI>9 among the three strategies, while concatenated Hp-RP is good at identifying peptides with pI<4. These advantages are useful when either basic or acidic peptides/proteins are analytical targets. The power of ERLIC in identification of basic peptides seems to be due to their efficient separation from acidic peptides. This study facilitates the choice of proper fractionation strategies based on specific objectives. For in-depth proteomic analysis of a cell, tissue and plasma, multidimensional liquid chromatography (MDLC) is still necessary to reduce sample complexity for improving analytical dynamic range and proteome coverage. This work conducts a direct comparison of three promising first-dimensional proteome fractionation methods. They are comparable in identifying proteins, but concatenated ERLIC and concatenated Hp-RP identify significantly more unique peptides than ERLIC. ERLIC is good at analyzing basic peptides, while concatenated Hp-RP performs the best in analyzing acidic peptides with pI<4. This will facilitate the choice of the proper peptide fractionation strategy based on a specific need. A combination of different fractionation strategies can be used to increase the sequence coverage and number of protein identification due to the complementary effect between different methods. Copyright © 2013 Elsevier B.V. All rights reserved.

Interventions for Weight Gain Prevention During the Transition to Young Adulthood: A review of the literature

PubMed Central

Laska, Melissa N.; Pelletier, Jennifer E.; Larson, Nicole I.; Story, Mary

2012-01-01

Purpose To review studies examining weight gain prevention interventions among young adults. Methods A snowball strategy was used to identify relevant studies, beginning with systematic PubMed, MEDLINE, PsychInfo, ERIC, and CINAHL searches. Included studies: (a) were published from 1985-2011, (b) were completed in the US or Canada, (a) focused on weight gain prevention among young adults ages 18-35 years, assessing weight, body mass index (BMI), body composition, diet or physical activity as an outcome, and (d) included pre- and post-intervention assessments. Results Thirty-seven interventions were identified. Ten interventions assessed weight, BMI, or body composition; twenty-seven addressed other relevant outcomes (e.g., diet, physical activity). Of the studies examining weight or body composition, six evaluated university courses or seminar-based interventions. Overall, many studies focused on individual-level intervention delivery and changes in weight-related knowledge and/or skills, though some incorporated relatively unique aspects (e.g., focusing on eating disorders and obesity simultaneously, using online technology, providing personalized feedback on weight change). Most showed promising results as small-scale pilot studies but lacked data from fully-powered randomized trials. Conclusions There is an urgent need to develop effective young adult-focused weight gain prevention strategies. This review identified promising areas for future work, though much additional research is needed. PMID:22443834

Building evaluation capacity in Ontario's public health units: promising practices and strategies.

PubMed

Bourgeois, I; Simmons, L; Buetti, D

2018-06-01

This article presents the findings of a project focusing on building evaluation capacity in 10 Ontario public health units. The study sought to identify effective strategies that lead to increased evaluation capacity in the participating organizations. This study used a qualitative, multiple case research design. An action research methodology was used to design customized evaluation capacity building (ECB) strategies for each participating organization, based on its specific context and needs. This methodological approach also enabled monitoring and assessment of each strategy, based on a common set of reporting templates. A multiple case study was used to analyze the findings from the 10 participating organizations and derive higher level findings. The main findings of the study show that most of the strategies used to increase evaluation capacity in public health units are promising, especially those focusing on developing the knowledge, skills, and attitudes of health unit staff and managers. Facilitators to ECB strategies were the engagement of all staff members, the support of leadership, and the existence of organizational tools and infrastructure to support evaluation. It is also essential to recognize that ECB takes time and resources to be successful. The design and implementation of ECB strategies should be based on organizational needs. These can be assessed using a standardized instrument, as well as interviews and staff surveys. The implementation of a multicomponent approach (i.e. several strategies implemented simultaneously) is also linked to better ECB outcomes in organizations. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

The impact of molecular targets in cancer drug development: major hurdles and future strategies.

PubMed

Hebar, Alexandra; Valent, Peter; Selzer, Edgar

2013-01-01

The last decades were characterized by enormous technological advances resulting in a better understanding of disease pathologies and improvement of treatment strategies. The development of targeted drugs, whose beginning can be traced back to Paul Ehrlich's theory of the 'magic bullet' approximately 100 years ago, is today widely appraised as a promising strategy to combat benign, as well as malignant, diseases. Over 40 years after US President Nixon declared the 'war on cancer', treatment outcome, especially of solid tumors in the advanced stages of disease, still lies far behind expectations. In this perspective article, the authors discuss the recent development of targeted cancer drugs and identify major hurdles. The authors further highlight future strategies that might improve and accelerate the drug-development process.

A novel strategy using MASCOT Distiller for analysis of cleavable isotope-coded affinity tag data to quantify protein changes in plasma.

PubMed

Leung, Kit-Yi; Lescuyer, Pierre; Campbell, James; Byers, Helen L; Allard, Laure; Sanchez, Jean-Charles; Ward, Malcolm A

2005-08-01

A novel strategy consisting of cleavable Isotope-Coded Affinity Tag (cICAT) combined with MASCOT Distiller was evaluated as a tool for the quantification of proteins in "abnormal" patient plasma, prepared by pooling samples from patients with acute stroke. Quantification of all light and heavy cICAT-labelled peptide ion pairs was obtained using MASCOT Distiller combined with a proprietary software. Peptides displaying differences were selected for identification by MS. These preliminary results show the promise of our approach to identify potential biomarkers.

An Exploratory Study of a New Educational Method Using Live Animals and Visual Thinking Strategies for Natural Science Teaching in Museums

ERIC Educational Resources Information Center

Genovesi, Jacqueline Sue

2011-01-01

The earth is in an environmental crisis that can only be addressed by changing human conservation attitudes. People must have the scientific knowledge to make informed decisions. Research identifying new promising practices, for the use of live animals that incorporate new theories of learning and factors proven to impact learning, is critical. …

Cognitive Strategy Instruction for Adolescents: What We Know about the Promise, What We Don't Know about the Potential

ERIC Educational Resources Information Center

Conley, Mark W.

2008-01-01

"Strategy instruction" is quickly becoming one of the most common--and perhaps the most commonly misunderstood--components of adolescent literacy research and practice. In this essay, veteran teacher educator Mark Conley argues that a particular type of strategy instruction known as cognitive strategy instruction holds great promise for improving…

The power and promise of applying genomics to honey bee health

PubMed Central

Robinson, Gene E.

2015-01-01

New genomic tools and resources are now being used to both understand honey bee health and develop tools to better manage it. Here, we describe the use of genomic approaches to identify and characterize bee parasites and pathogens, examine interactions among these parasites and pathogens, between them and their bee hosts, and to identify genetic markers for improved breeding of more resilient bee stocks. We also discuss several new genomic techniques that can be used to more efficiently study, monitor and improve bee health. In the case of using RNAi-based technologies to mitigate diseases in bee populations, we highlight advantages, disadvantages and strategies to reduce risk. The increased use of genomic analytical tools and manipulative technologies has already led to significant advances, and holds great promise for improvements in the health of honey bees and other critical pollinator species. PMID:26273565

Exploring the use of concept chains to structure teacher trainees' understanding of science

NASA Astrophysics Data System (ADS)

Machin, Janet; Varleys, Janet; Loxley, Peter

2004-12-01

This paper reports on a paper and pencil concept-sorting strategy that enables trainee teachers to restructure their knowledge in any one domain of science. It is used as a self-study tool, mainly to enable them to break down and understand the progression of concepts beyond the level at which they have to teach. The strategy involves listing key ideas in an increasingly complex and inclusive fashion such that a 'chain' is developed where the initial statements are simple and the final ones more complex. Evaluation of the strategy with trainees over a five-year period revealed promising potential for the strategy as a self-study tool, as well as an audit tool, enabling tutors to more easily identify misconceptions. There was some evidence that trainees found the strategy useful in preparing themselves to teach in the classroom, possibly by enabling meaningful learning to take place according to the Ausubel-Novak-Gowin theory.

Feasibility of a cognitive strategy training intervention for people with Parkinson's disease.

PubMed

Foster, Erin R; Spence, Daniel; Toglia, Joan

2018-05-01

To investigate the feasibility of a novel client-centered cognitive strategy training intervention for people with Parkinson's disease (PD). This was a case series of seven people with PD without dementia but with subjective cognitive decline. The intervention involved ≥5 treatment sessions at the participant's home. Participant acceptance and engagement were assessed by the Credibility/Expectancy Questionnaire (CEQ), Client Satisfaction Questionnaire (CSQ), enjoyment and effort ratings, and homework completion. Logistical information was tracked, and the Canadian Occupational Performance Measure (COPM) was an exploratory outcome measure. Data analysis was descriptive. CEQ scores were positive and increased over time. CSQ scores were high (M = 30.8, SD = 0.75), with all participants rating all items positively. Almost all (95%) effort and enjoyment ratings were ≥3 (Much), and homework completion rates averaged 84% (SD = 18). Intervention duration was 6-15 weeks (M = 9.2, SD = 2.8), with treatment sessions averaging 1.7 h (SD = 0.5). Group and most individual COPM ratings improved ≥2 points. These findings support the feasibility of the intervention for people with PD. It was acceptable, engaging, and promising in terms of its effect on self-identified functional cognitive problems. Implications for Rehabilitation People with Parkinson's disease (PD) without dementia can experience cognitive decline that negatively impacts function and quality of life. Strategy-based interventions that explicitly train for transfer may mitigate the negative functional consequences of cognitive decline in this population. We developed a client-centered cognitive strategy training intervention for people with PD. This small case series supports its feasibility, indicating that it is acceptable and engaging for people with PD and promising in terms of its effect on self-identified functional cognitive problems.

Metabolomics-based promising candidate biomarkers and pathways in Alzheimer's disease.

PubMed

Kang, Jian; Lu, Jingli; Zhang, Xiaojian

2015-05-01

Pathologically, loss of synapses and neurons, extracellular senile plaques and intracellular neurofibrillary tangles (NFTs) are observed in the brains of patients with Alzheimer's disease (AD). These features are associated with changes Aβ (amyloid β) 40, Aβ42, total tau and phosphorylated tau (p-tau), which are as definitely biomarkers for severe AD state. However, biomarkers for effectively diagnosing AD in the pre-clinical state for directing therapeutic strategies are lacking. Metabolic profiling as a powerful tool to identify new biomarkers is receiving increasing attention in AD. This review will focus on metabolomics-based detection of promising candidate biomarkers and pathways in AD to facilitate the discovery of new medicines and disease pathways.

Proteomic analysis of Chlorella vulgaris: Potential targets for enhanced lipid accumulation

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

Guarnieri, Michael T.; Nag, Ambarish; Yang, Shihui

2013-11-01

Oleaginous microalgae are capable of producing large quantities of fatty acids and triacylglycerides. As such, they are promising feedstocks for the production of biofuels and bioproducts. Genetic strain-engineering strategies offer a means to accelerate the commercialization of algal biofuels by improving the rate and total accumulation of microalgal lipids. However, the industrial potential of these organisms remains to be met, largely due to the incomplete knowledgebase surrounding the mechanisms governing the induction of algal lipid biosynthesis. Such strategies require further elucidation of genes and gene products controlling algal lipid accumulation. In this study, we have set out to examine thesemore » mechanisms and identify novel strain-engineering targets in the oleaginous microalga, Chlorella vulgaris. Comparative shotgun proteomic analyses have identified a number of novel targets, including previously unidentified transcription factors and proteins involved in cell signaling and cell cycle regulation. These results lay the foundation for strain-improvement strategies and demonstrate the power of translational proteomic analysis.« less

Adolescent Drug Use Prevention: Common Features of Promising Community Programs. Report to the Chairman, Subcommittee on Select Education, Committee on Education and Labor, House of Representatives.

ERIC Educational Resources Information Center

General Accounting Office, Washington, DC. Program Evaluation and Methodology Div.

The importance of identifying effective drug abuse prevention strategies is clear not only from the increasing federal expenses, but also from the costs to individuals and families, and the overall damage to U.S. productivity and competitiveness caused by drug use. This report is about comprehensive community-based approaches to drug abuse…

The landscape of knowledge translation interventions in cancer control: What do we know and where to next? A review of systematic reviews

PubMed Central

2011-01-01

Background Effective implementation strategies are needed to optimize advancements in the fields of cancer diagnosis, treatment, survivorship, and end-of-life care. We conducted a review of systematic reviews to better understand the evidentiary base of implementation strategies in cancer control. Methods Using three databases, we conducted a search and identified English-language systematic reviews published between 2005 and 2010 that targeted consumer, professional, organizational, regulatory, or financial interventions, tested exclusively or partially in a cancer context (primary focus); generic or non-cancer-specific reviews were also considered. Data were extracted, appraised, and analyzed by members of the research team, and research ideas to advance the field were proposed. Results Thirty-four systematic reviews providing 41 summaries of evidence on 19 unique interventions comprised the evidence base. AMSTAR quality ratings ranged between 2 and 10. Team members rated most of the interventions as promising and in need of further research, and 64 research ideas were identified. Conclusions While many interventions show promise of effectiveness in the cancer-control context, few reviews were able to conclude definitively in favor of or against a specific intervention. We discuss the complexity of implementation research and offer suggestions to advance the science in this area. PMID:22185329

Strategies for successful recruitment of young adults to healthy lifestyle programmes for the prevention of weight gain: a systematic review.

PubMed

Lam, E; Partridge, S R; Allman-Farinelli, M

2016-02-01

Recruiting healthy young adults, aged 18-35, to lifestyle programmes for prevention of weight gain is challenging but important given their increasing rates of obesity. This review aimed to examine the success of different recruitment strategies. A systematic literature search identified 26 separate studies using 10 electronic databases. Participant characteristics and efficacy of interventions were well reported in all studies, but reporting of recruitment procedures, costs, times and effectiveness was minimal. Of those reporting recruitment, both active (e.g. face-to-face) and passive (e.g. print-media and mass-mailings) approaches were identified with the latter most frequently employed. Novel strategies such as social media and marketing approaches were identified. Television and radio have potentially high reach but low efficiency with high cost compared with mass-mailings which yield high numbers of participants. Marketing campaigns appeared to be a promising approach. Incentives demonstrated enhanced recruitment. The use of formative research to guide recruitment strategies for interventions is recommended. Reporting of success, cost and timelines for recruitment should be included in reporting of future trials. This first synthesis of recruitment information can be used to inform recruitment frameworks for lifestyle programmes seeking to attract young adults. © 2015 World Obesity.

Can cognitive behavioural therapy based strategies be integrated into physiotherapy for the prevention of chronic low back pain? A systematic review.

PubMed

Brunner, Emanuel; De Herdt, Amber; Minguet, Philippe; Baldew, Se-Sergio; Probst, Michel

2013-01-01

The primary purpose was to detect randomized controlled trials investigating cognitive behaviour therapy-based (CBT) treatments applied in acute/sub-acute low back pain (LBP). The secondary purpose was to analyse the methodological properties of the included studies, and to identify theory-based treatment strategies that are applicable for physiotherapists. A systematic literature search was conducted using four databases. Risk of bias of included studies was assessed and the methodological properties summarized. In addition, content and treatment theory of detected CBT-based strategies were systematically analysed and classified into three distinctive concepts of CBT: operant, cognitive and respondent treatment. Finally, applicability of treatment strategies in physiotherapy practice was discussed. Eight studies were included in the present systematic review. Half of the studies suffered from high risk of bias, and study characteristics varied in all domains of methodology, particularly in terms of treatment design and outcome measures. Graded activity, an operant treatment approach based on principles of operant conditioning, was identified as a CBT-based strategy with traceable theoretical justification that can be applied by physiotherapists. Operant conditioning can be integrated in ambulant physiotherapy practice and is a promising CBT-based strategy for the prevention of chronic LBP.

Past Strategies and Future Directions for Identifying AMP-Activated Protein Kinase (AMPK) Modulators

PubMed Central

Sinnett, Sarah E.; Brenman, Jay E.

2014-01-01

AMP-activated protein kinase (AMPK) is a promising therapeutic target for cancer, type II diabetes, and other illnesses characterized by abnormal energy utilization. During the last decade, numerous labs have published a range of methods for identifying novel AMPK modulators. The current understanding of AMPK structure and regulation, however, has propelled a paradigm shift in which many researchers now consider ADP to be an additional regulatory nucleotide of AMPK. How can the AMPK community apply this new understanding of AMPK signaling to translational research? Recent insights into AMPK structure, regulation, and holoenzyme-sensitive signaling may provide the hindsight needed to clearly evaluate the strengths and weaknesses of past AMPK drug discovery efforts. Improving future strategies for AMPK drug discovery will require pairing the current understanding of AMPK signaling with improved experimental designs. PMID:24583089

A systematic review investigating the behaviour change strategies in interventions to prevent misuse of anabolic steroids.

PubMed

Bates, Geoff; Begley, Emma; Tod, David; Jones, Lisa; Leavey, Conan; McVeigh, Jim

2017-10-01

We examined intervention effectiveness of strategies to prevent image- and performance-enhancing drug use. Comprehensive searches identified 14 interventions that met review inclusion criteria. Interventions were predominantly educational and delivered within school sport settings, but targeted a wide range of mediating factors. Identification of effective components was limited across studies by brief or imprecise descriptions of intervention content, lack of behavioural outcome measures and short-term follow-up times. However, studies with components in addition to information provision may be more promising. Interventions outside of sport settings are required to reflect the transition of this form of substance use to the general population.

Using focus groups and social marketing to strengthen promotion of group prenatal care.

PubMed

Vonderheid, Susan C; Carrie, S Klima; Norr, Kathleen F; Grady, Mary Alice; Westdahl, Claire M

2013-01-01

Centering Pregnancy, an innovative group model of prenatal care, shows promise to reduce persistent adverse maternal-infant outcomes and contain costs. Because this innovation requires systemwide change, clinics reported needing support enrolling women into groups and obtaining organizational buy-in. This study used the 3-step social marketing communication strategy to help clinic staff identify key customers and customer-specific barriers to adopting or supporting Centering Pregnancy. They developed targeted information to reduce barriers and built skills in communicating with different customers through role-playing. Findings provide practical information for others to use this communication strategy to improve implementation of Centering Pregnancy.

Rejuvenating Strategies for Stem Cell-based Therapies in Aging

PubMed Central

Neves, Joana; Sousa-Victor, Pedro; Jasper, Heinrich

2017-01-01

SUMMARY Recent advances in our understanding of tissue regeneration and the development of efficient approaches to induce and differentiate pluripotent stem cells for cell replacement therapies promise exciting avenues for treating degenerative age-related diseases. However, clinical studies and insights from model organisms have identified major roadblocks that normal aging processes impose on tissue regeneration. These new insights suggest that specific targeting of environmental niche components, including growth factors, ECM and immune cells, and intrinsic stem cell properties that are affected by aging will be critical for development of new strategies to improve stem cell function and optimize tissue repair processes. PMID:28157498

Genomics in Primary and Secondary Prevention of Pancreatic Cancer.

PubMed

Malats, Núria; Molina-Montes, Esther; La Vecchia, Carlo

2017-01-01

Pancreatic cancer (PC) is one of the deadliest cancers worldwide for which little clinical progress has been made in the last decades. Furthermore, increased trends of PC mortality rates have been reported in Westernised countries. PC is usually diagnosed in advanced stages, precluding patients of an effective treatment. Identifying high-risk populations and early detection markers is the first and crucial step to impact on these figures and change the PC horizon. To discuss the published body of evidence on host and tumor genomics promising markers for primary and/or secondary personalised PC prevention, as well as the future perspectives in the field. A review of the literature was performed to identify germline and tumor DNA and RNA markers that showed potential usefulness in defining the high-risk population, diagnosing the disease early, and identifying new carcinogens associated with PC. Only high-penetrance inherited mutations are used, at present, to define the high-risk PC population. Although there are some promising genomics markers to be used as early detection tests, none has been validated adequately to be integrated into the clinics routine. Despite of important efforts made in the recent time, little progress has been made to better characterise high-risk PC populations and to identify genomics-based markers for its early diagnosis. PC rates continue to rise, and this disease is becoming a real public health problem in the Westernised world. International and multidisciplinary strategies to identify new markers and properly validate the promising ones are urgently needed to implement cost-efficient primary and secondary prevention interventions in PC. © 2017 S. Karger AG, Basel.

Strategies for reducing treatment default in drug-resistant tuberculosis: systematic review and meta-analysis.

PubMed

Toczek, A; Cox, H; du Cros, P; Cooke, G; Ford, N

2013-03-01

Scaling up treatment for multidrug-resistant tuberculosis is a global health priority. However, current treatment regimens are long and associated with side effects, and default rates are consequently high. This systematic review aimed to identify strategies for reducing treatment default. We conducted a systematic search up to May 2012 to identify studies describing interventions to support patients receiving treatment for multidrug-resistant tuberculosis (MDR-TB). The potential influence of study interventions were explored through subgroup analyses. A total of 75 studies provided outcomes for 18,294 patients across 31 countries. Default rates ranged from 0.5% to 56%, with a pooled proportion of 14.8% (95%CI 12.4-17.4). Strategies identified to be associated with lower default rates included the engagement of community health workers as directly observed treatment (DOT) providers, the provision of DOT throughout treatment, smaller cohort sizes and the provision of patient education. Current interventions to support adherence and retention are poorly described and based on weak evidence. This review was able to identify a number of promising, inexpensive interventions feasible for implementation and scale-up in MDR-TB programmes. The high default rates reported from many programmes underscore the pressing need to further refine and evaluate simple intervention packages to support patients.

Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

PubMed Central

Sibille, KT; Bartsch, F; Reddy, D; Fillingim, RB; Keil, A

2016-01-01

Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promoting adaptive, treatment responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain’s response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimizing learning and positive central nervous system (CNS) adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research however has identified a wide spectrum of methods that can be used to “re-open” and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, which are non-invasive, inexpensive to administer, implementable in numerous settings, and may be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, providing evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain. PMID:26848123

Expert views on most suitable monetary incentives on food to stimulate healthy eating.

PubMed

Waterlander, Wilma E; Steenhuis, Ingrid H M; de Vet, Emely; Schuit, Albertine J; Seidell, Jacob C

2010-06-01

Pricing strategies are an important component in the marketing mix and may also be useful in stimulating healthier food choices. However, due to competing interests and feasibility problems, the introduction of pricing strategies is complicated. For successfully introducing food pricing strategies, it is essential to explore incentives that are not only promising but also realizable and being approved by different sectors. We aimed to assemble a list of pricing strategies by exploring expert views using the Delphi method. Subjects included experts from academia, industry, retail, agriculture, policymakers, consumers and non-governmental organizations. Data were collected in three rounds. In round one, experts designed promising pricing strategies. Based on a time-budget model incorporating Sleep, Leisure, Occupation, Transportation and Home-based activities, these strategies were in the subsequent rounds judged on several criteria. Results were analysed using median and interquartile deviations scores. We found fair consensus levels among experts and a varied list of promising pricing strategies. The panel agreed on the potential success of offering small presents, providing price-cuts on healthy foods and discounting healthier foods more frequently. Also, it was found that experts gave higher rates to pricing strategies for which the implementation responsibilities could be placed elsewhere. The resulted list of promising monetary incentives is an essential first step for the future design of pricing strategies. Following this study, it is important to determine how to make solid agreements on responsibility and implementation issues. Also, consumer perceptions regarding the proposed pricing strategies should be studied.

Strategies for Building Peer Surgical Coaching Relationships.

PubMed

Beasley, Heather L; Ghousseini, Hala N; Wiegmann, Douglas A; Brys, Nicole A; Pavuluri Quamme, Sudha R; Greenberg, Caprice C

2017-04-19

Peer surgical coaching is a promising approach for continuing professional development. However, scant guidance is available for surgeons seeking to develop peer-coaching skills. Executive coaching research suggests that effective coaches first establish a positive relationship with their coachees by aligning role and process expectations, establishing rapport, and cultivating mutual trust. To identify the strategies used by peer surgical coaches to develop effective peer-coaching relationships with their coachees. Drawing on executive coaching literature, a 3-part framework was developed to examine the strategies peer surgical coaches (n = 8) used to initially cultivate a relationship with their coachees (n = 11). Eleven introductory 1-hour meetings between coaching pairs participating in a statewide surgical coaching program were audiorecorded, transcribed, and coded on the basis of 3 relationship-building components. Once coded, thematic analysis was used to organize coded strategies into thematic categories and subcategories. Data were collected from October 10, 2014, to March 20, 2015. Data analysis took place from May 26, 2015, to July 20, 2016. Strategies and potentially counterproductive activities for building peer-coaching relationships in the surgical context to inform the future training of surgical coaches. Coaches used concrete strategies to align role and process expectations about the coaching process, to establish rapport, and to cultivate mutual trust with their coachees during introductory meetings. Potential coaching pitfalls are identified that could interfere with each of the 3 relationship-building components. Peer-nominated surgical coaches were provided with training on abstract concepts that underlie effective coaching practices in other fields. By identifying the strategies used by peer surgical coaches to operationalize these concepts, empirically based strategies to inform other surgical coaching programs are provided.

Identification of multiple novel protein biomarkers shed by human serous ovarian tumors into the blood of immunocompromised mice and verified in patient sera.

PubMed

Beer, Lynn A; Wang, Huan; Tang, Hsin-Yao; Cao, Zhijun; Chang-Wong, Tony; Tanyi, Janos L; Zhang, Rugang; Liu, Qin; Speicher, David W

2013-01-01

The most cancer-specific biomarkers in blood are likely to be proteins shed directly by the tumor rather than less specific inflammatory or other host responses. The use of xenograft mouse models together with in-depth proteome analysis for identification of human proteins in the mouse blood is an under-utilized strategy that can clearly identify proteins shed by the tumor. In the current study, 268 human proteins shed into mouse blood from human OVCAR-3 serous tumors were identified based upon human vs. mouse species differences using a four-dimensional plasma proteome fractionation strategy. A multi-step prioritization and verification strategy was subsequently developed to efficiently select some of the most promising biomarkers from this large number of candidates. A key step was parallel analysis of human proteins detected in the tumor supernatant, because substantially greater sequence coverage for many of the human proteins initially detected in the xenograft mouse plasma confirmed assignments as tumor-derived human proteins. Verification of candidate biomarkers in patient sera was facilitated by in-depth, label-free quantitative comparisons of serum pools from patients with ovarian cancer and benign ovarian tumors. The only proteins that advanced to multiple reaction monitoring (MRM) assay development were those that exhibited increases in ovarian cancer patients compared with benign tumor controls. MRM assays were facilely developed for all 11 novel biomarker candidates selected by this process and analysis of larger pools of patient sera suggested that all 11 proteins are promising candidate biomarkers that should be further evaluated on individual patient blood samples.

77 FR 56194 - Promising and Practical Strategies to Increase Postsecondary Success; Request for Information

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-12

.../Remedial Education Digital Materials Disability Services Dual Degrees Earn and Learn Efficiency Employer... Accelerated Learning Accessible Materials Achievement Gap Closure Adult Education Affordability Assessment... DEPARTMENT OF EDUCATION Promising and Practical Strategies to Increase Postsecondary Success...

Assessing university students' self-efficacy to employ alcohol-related harm reduction strategies.

PubMed

Rosenberg, Harold; Bonar, Erin E; Hoffmann, Erica; Kryszak, Elizabeth; Young, Kathleen M; Kraus, Shane W; Ashrafioun, Lisham; Bannon, Erin E; Pavlick, Michelle

2011-01-01

Develop and evaluate key psychometric properties of a self-report questionnaire specifically designed to assess student drinkers' self-confidence to employ a variety of strategies intended to reduce unhealthy consequences of high-risk drinking. Four hundred ninety-eight participants rated their confidence (from "not at all confident" to "completely confident") to employ 17 harm reduction strategies when drinking. Factor analysis and internal consistency reliability analyses indicated that the 17 items constitute a single scale with good test-retest reliability. Consistent with other research examining previous use of such strategies, women in our sample reported significantly higher harm reduction self-efficacy than did men. Harm reduction self-efficacy was also associated with reported number of high-risk drinking episodes in the previous 2 weeks. This brief and easily administered questionnaire holds promise as a clinical tool to identify individuals with low harm reduction self-efficacy and as an outcome measure for health promotion and educational interventions.

Promising Targets in Anti-cancer Drug Development: Recent Updates.

PubMed

Kumar, Bhupinder; Singh, Sandeep; Skvortsova, Ira; Kumar, Vinod

2017-01-01

Cancer is a multifactorial disease and its genesis and progression are extremely complex. The biggest problem in the anticancer drug development is acquiring of multidrug resistance and relapse. Classical chemotherapeutics directly target the DNA of the cell, while the contemporary anticancer drugs involve molecular-targeted therapy such as targeting the proteins possessing abnormal expression inside the cancer cells. Conventional strategies for the complete eradication of the cancer cells proved ineffective. Targeted chemotherapy was successful in certain malignancies however, the effectiveness has often been limited by drug resistance and side effects on normal tissues and cells. Since last few years, many promising drug targets have been identified for the effective treatment of cancer. The current review article describes some of these promising anticancer targets that include kinases, tubulin, cancer stem cells, monoclonal antibodies and vascular targeting agents. In addition, promising drug candidates under various phases of clinical trials are also described. Multi-acting drugs that simultaneously target different cancer cell signaling pathways may facilitate the process of effective anti-cancer drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The effects of workplace physical activity interventions in men: a systematic review.

PubMed

Wong, Jason Y L; Gilson, Nicholas D; van Uffelen, Jannique G Z; Brown, Wendy J

2012-07-01

The workplace is cited as a promising setting for physical activity (PA) promotion, but workplace PA interventions tend not to specifically target men. The aim of this article was to review the literature on workplace PA interventions for men and to identify key issues for future intervention development. Articles targeting PA at the workplace were located through a structured database search. Information on intervention strategies and PA outcomes were extracted. Only 13 studies (10.5%) reviewed focused on men, of which 5 showed significant increases in PA. These studies used generic, multicomponent, health promotion strategies with a variety of timeframes, self-report PA measures, and PA outcomes. The systematic review identified that evidence on the effectiveness of workplace PA interventions for men is equivocal and highlighted methodological concerns. Future research should use reliable and valid measures of PA and interventions that focus specifically on men's needs and PA preferences.

Effective Strategies for Monitoring and Regulating Chemical Mixtures and Contaminants Sharing Pathways of Toxicity

PubMed Central

Venkatesan, Arjun K.; Halden, Rolf U.

2015-01-01

Traditionally, hazardous chemicals have been regulated in the U.S. on a one-by-one basis, an approach that is slow, expensive and can be inefficient, as illustrated by a decades-long succession of replacing one type of organohalogen flame retardants (OHFRs) with another one, without addressing the root cause of toxicity and associated public health threats posed. The present article expounds on the need for efficient monitoring strategies and pragmatic steps in reducing environmental pollution and adverse human health impacts. A promising approach is to combine specific bioassays with state-of-the-art chemical screening to identify chemicals and chemical mixtures sharing specific modes of action (MOAs) and pathways of toxicity (PoTs). This approach could be used to identify and regulate hazardous chemicals as classes or compound families, featuring similar biological end-points, such as endocrine disruption and mutagenicity. Opportunities and potential obstacles of implementing this approach are discussed. PMID:26343697

Obstructive sleep apnea in North American commercial drivers.

PubMed

Kales, Stefanos N; Straubel, Madeleine G

2014-01-01

The most common medical cause of excessive daytime sleepiness (EDS) is obstructive sleep apnea (OSA). Specifically, among an estimated 14 million US commercial drivers, 17-28% or 2.4 to 3.9 million are expected to have OSA. Based on existing epidemiologic evidence, most of these drivers are undiagnosed and not adequately treated. Untreated OSA increases the risk of vehicular crashes as documented in multiple independent studies and by meta-analysis. Therefore, identifying commercial drivers with OSA and having them effectively treated should decrease crash-related fatalities and injuries. Several strategies are available for screening and identifying drivers with OSA. The simplest and most effective objective strategies use body mass index (BMI) cutoffs for obesity. Functional screens are promising adjuncts to other objective tests. The most effective approach will likely be a combination of a good questionnaire; BMI measures; and a careful physician-obtained history complemented by a functional screen.

Enriched pathways for major depressive disorder identified from a genome-wide association study.

PubMed

Kao, Chung-Feng; Jia, Peilin; Zhao, Zhongming; Kuo, Po-Hsiu

2012-11-01

Major depressive disorder (MDD) has caused a substantial burden of disease worldwide with moderate heritability. Despite efforts through conducting numerous association studies and now, genome-wide association (GWA) studies, the success of identifying susceptibility loci for MDD has been limited, which is partially attributed to the complex nature of depression pathogenesis. A pathway-based analytic strategy to investigate the joint effects of various genes within specific biological pathways has emerged as a powerful tool for complex traits. The present study aimed to identify enriched pathways for depression using a GWA dataset for MDD. For each gene, we estimated its gene-wise p value using combined and minimum p value, separately. Canonical pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta were used. We employed four pathway-based analytic approaches (gene set enrichment analysis, hypergeometric test, sum-square statistic, sum-statistic). We adjusted for multiple testing using Benjamini & Hochberg's method to report significant pathways. We found 17 significantly enriched pathways for depression, which presented low-to-intermediate crosstalk. The top four pathways were long-term depression (p⩽1×10-5), calcium signalling (p⩽6×10-5), arrhythmogenic right ventricular cardiomyopathy (p⩽1.6×10-4) and cell adhesion molecules (p⩽2.2×10-4). In conclusion, our comprehensive pathway analyses identified promising pathways for depression that are related to neurotransmitter and neuronal systems, immune system and inflammatory response, which may be involved in the pathophysiological mechanisms underlying depression. We demonstrated that pathway enrichment analysis is promising to facilitate our understanding of complex traits through a deeper interpretation of GWA data. Application of this comprehensive analytic strategy in upcoming GWA data for depression could validate the findings reported in this study.

Assessing self-efficacy to reduce one's drinking: further evaluation of the Alcohol Reduction Strategies-Current Confidence questionnaire.

PubMed

Kraus, Shane W; Rosenberg, Harold; Bonar, Erin E; Hoffmann, Erica; Kryszak, Elizabeth; Young, Kathleen M; Ashrafioun, Lisham; Bannon, Erin E

2012-01-01

To evaluate the psychometric properties of a previously published questionnaire designed to assess young drinkers' self-efficacy to employ 31 cognitive-behavioral alcohol reduction strategies. Undergraduates (n = 353) recruited from a large Midwestern university completed the previously published Alcohol Reduction Strategies-Current Confidence questionnaire (and other measures) for a self-selected heavy drinking setting. Item loadings from a principal components analysis, a high internal consistency reliability coefficient, and a moderate mean inter-item correlation suggested that all 31 items comprised a single scale. Correlations of questionnaire scores with selected aspects of drinking history and personality provided support for criterion and discriminant validity, respectively. Women reported higher current confidence to use these strategies than did men, but current confidence did not vary as a function of recent binge status. Given this further demonstration of its psychometric qualities, this questionnaire holds promise as a clinical tool to identify clients who lack confidence in their ability to employ cognitive-behavioral coping strategies to reduce their drinking.

Curcumin and Resveratrol as Promising Natural Remedies with Nanomedicine Approach for the Effective Treatment of Triple Negative Breast Cancer

PubMed Central

Shindikar, Amol; Singh, Akshita; Nobre, Malcolm; Kirolikar, Saurabh

2016-01-01

Researchers have made considerable progress in last few decades in understanding mechanisms underlying pathogenesis of breast cancer, its phenotypes, its molecular and genetic changes, its physiology, and its prognosis. This has allowed us to identify specific targets and design appropriate chemical entities for effective treatment of most breast cancer phenotypes, resulting in increased patient survivability. Unfortunately, these strategies have been largely ineffective in the treatment of triple negative breast cancer (TNBC). Hormonal receptors lacking render the conventional breast cancer drugs redundant, forcing scientists to identify novel targets for treatment of TNBC. Two natural compounds, curcumin and resveratrol, have been widely reported to have anticancer properties. In vitro and in vivo studies show promising results, though their effectiveness in clinical settings has been less than satisfactory, owing to their feeble pharmacokinetics. Here we discuss these naturally occurring compounds, their mechanism as anticancer agents, their shortcomings in translational research, and possible methodology to improve their pharmacokinetics/pharmacodynamics with advanced drug delivery systems. PMID:27242900

The Business, Ethics, and Quality Cases for Consumer Engagement in Nursing.

PubMed

Hassmiller, Susan; Bilazarian, Ani

2018-04-01

The aims of this study were to illustrate the quality, safety, cost-effectiveness, and ethics of consumer engagement initiatives and identify promising practices and leadership strategies used by nursing leaders. A literature review was performed with supplementary interviews conducted with 25 key nursing informants including nursing executives and chief nursing officers at acute care hospitals, community health centers, policy institutions, and quality and safety organizations. A narrative synthesis approach was used to identify and compare existing measures of consumer engagement and compassionate care in acute care settings. One-hour semistructured interviews were performed, and information was gathered by notes and audio recordings. Consumer engagement activities focusing on compassionate patient and provider interactions involving patients and family as partners on the care team are associated with increases in treatment savings and patient safety in terms of length of stay and reduced medication errors. Engagement initiatives support employee health and reduce compassion fatigue. Findings illustrate the impact of patients and family engagement in decision making and promising organizational practices that reinforce engagement.

Experimental Models to Study the Role of Microbes in Host-Parasite Interactions.

PubMed

Hahn, Megan A; Dheilly, Nolwenn M

2016-01-01

Until recently, parasitic infections have been primarily studied as interactions between the parasite and the host, leaving out crucial players: microbes. The recent realization that microbes play key roles in the biology of all living organisms is not only challenging our understanding of host-parasite evolution, but it also provides new clues to develop new therapies and remediation strategies. In this paper we provide a review of promising and advanced experimental organismal systems to examine the dynamic of host-parasite-microbe interactions. We address the benefits of developing new experimental models appropriate to this new research area and identify systems that offer the best promises considering the nature of the interactions among hosts, parasites, and microbes. Based on these systems, we identify key criteria for selecting experimental models to elucidate the fundamental principles of these complex webs of interactions. It appears that no model is ideal and that complementary studies should be performed on different systems in order to understand the driving roles of microbes in host and parasite evolution.

Supporting Patient Behavior Change: Approaches Used by Primary Care Clinicians Whose Patients Have an Increase in Activation Levels.

PubMed

Greene, Jessica; Hibbard, Judith H; Alvarez, Carmen; Overton, Valerie

2016-03-01

We aimed to identify the strategies used to support patient behavior change by clinicians whose patients had an increase in patient activation. This mixed methods study was conducted in collaboration with Fairview Health Services, a Pioneer Accountable Care Organization. We aggregated data on the change in patient activation measure (PAM) score for 7,144 patients to the primary care clinician level. We conducted in-depth interviews with 10 clinicians whose patients' score increases were among the highest and 10 whose patients' score changes were among the lowest. Transcripts of the interviews were analyzed to identify key strategies that differentiated the clinicians whose patients had top PAM change scores. Clinicians whose patients had relatively large activation increases reported using 5 key strategies to support patient behavior change (mean = 3.9 strategies): emphasizing patient ownership; partnering with patients; identifying small steps; scheduling frequent follow-up visits to cheer successes, problem solve, or both; and showing caring and concern for patients. Clinicians whose patients had lesser change in activation were far less likely to describe using these approaches (mean = 1.3 strategies). Most clinicians, regardless of group, reported developing their own approach to support patient behavior change. Those whose patients showed high activation change reported spending more time with patients on counseling and education than did those whose patients showed less improvement in activation. Clinicians vary in the strategies they use to promote behavior change and in the time spent with patients on such activities. The 5 key strategies used by clinicians with high patient activation change are promising approaches to supporting patient behavior change that should be tested in a larger sample of clinicians to validate their effectiveness. © 2016 Annals of Family Medicine, Inc.

Imaging free zinc levels in vivo - what can be learned?

PubMed

De Leon-Rodriguez, Luis; Lubag, Angelo Josue M; Sherry, A Dean

2012-12-01

Our ever-expanding knowledge about the role of zinc in biology includes its role in redox modulation, immune response, neurotransmission, reproduction, diabetes, cancer, and Alzheimers disease is galvanizing interest in detecting and monitoring the various forms of Zn(II) in biological systems. This paper reviews reported strategies for detecting and tracking of labile or "free" unchelated Zn(II) in tissues. While different bound structural forms of Zn(II) have been identified and studied in vitro by multiple techniques, very few molecular imaging methods have successfully tracked the ion in vivo. A number of MRI and optical strategies have now been reported for detection of free Zn(II) in cells and tissues but only a few have been applied successfully in vivo. A recent report of a MRI sensor for in vivo tracking of Zn(II) released from pancreatic β-cells during insulin secretion exemplifies the promise of rational design of new Zn(II) sensors for tracking this biologically important ion in vivo. Such studies promise to provide new insights into zinc trafficking in vivo and the critical role of this ion in many human diseases.

Targeting LKB1 in cancer – exposing and exploiting vulnerabilities

PubMed Central

Momcilovic, M; Shackelford, D B

2015-01-01

The LKB1 tumour suppressor is a serine/threonine kinase that functions as master regulator of cell growth, metabolism, survival and polarity. LKB1 is frequently mutated in human cancers and research spanning the last two decades have begun decoding the cellular pathways deregulated following LKB1 inactivation. This work has led to the identification of vulnerabilities present in LKB1-deficient tumour cells. Pre-clinical studies have now identified therapeutic strategies targeting this subset of tumours that promise to benefit this large patient population harbouring LKB1 mutations. Here, we review the current efforts that are underway to translate pre-clinical discovery of therapeutic strategies targeting LKB1 mutant cancers into clinical practice. PMID:26196184

Reserve design to maximize species persistence

Treesearch

Robert G. Haight; Laurel E. Travis

2008-01-01

We develop a reserve design strategy to maximize the probability of species persistence predicted by a stochastic, individual-based, metapopulation model. Because the population model does not fit exact optimization procedures, our strategy involves deriving promising solutions from theory, obtaining promising solutions from a simulation optimization heuristic, and...

Anal cancer and intraepithelial neoplasia screening: A review

PubMed Central

Leeds, Ira L; Fang, Sandy H

2016-01-01

This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations. PMID:26843912

Improving medication adherence among community-dwelling seniors with cognitive impairment: a systematic review of interventions.

PubMed

Kröger, Edeltraut; Tatar, Ovidiu; Vedel, Isabelle; Giguère, Anik M C; Voyer, Philippe; Guillaumie, Laurence; Grégoire, Jean-Pierre; Guénette, Line

2017-08-01

Background Medication non-adherence may lead to poor therapeutic outcomes. Cognitive functions deteriorate with age, contributing to decreased adherence. Interventions have been tested to improve adherence in seniors with cognitive impairment or Alzheimer disease (AD), but high-quality systematic reviews are lacking. It remains unclear which interventions are promising. Objectives We conducted a systematic review to identify, describe, and evaluate interventions aimed at improving medication adherence among seniors with any type of cognitive impairment. Methods Following NICE guidance, databases and websites were searched using combinations of controlled and free vocabulary. All adherence-enhancing interventions and study designs were considered. Studies had to include community dwelling seniors, aged 65 years or older, with cognitive impairment, receiving at least one medication for a chronic condition, and an adherence measure. Study characteristics and methodological quality were assessed. Results We identified 13 interventions, including six RCTs. Two studies were of poor, nine of low/medium and two of high quality. Seven studies had sample sizes below 50 and six interventions focused on adherence to AD medication. Six interventions tested a behavioral, four a medication oriented, two an educational and one a multi-faceted approach. Studies rarely assessed therapeutic outcomes. All but one intervention showed improved adherence. Conclusion Three medium quality studies showed better adherence with patches than with pills for AD treatment. Promising interventions used educational or reminding strategies, including one high quality RCT. Nine studies were of low/moderate quality. High quality RCTs using a theoretical framework for intervention selection are needed to identify strategies for improved adherence in these seniors.

Repositioning drugs for inflammatory disease – fishing for new anti-inflammatory agents

PubMed Central

Hall, Christopher J.; Wicker, Sophie M.; Chien, An-Tzu; Tromp, Alisha; Lawrence, Lisa M.; Sun, Xueying; Krissansen, Geoffrey W.; Crosier, Kathryn E.; Crosier, Philip S.

2014-01-01

Inflammation is an important and appropriate host response to infection or injury. However, dysregulation of this response, with resulting persistent or inappropriate inflammation, underlies a broad range of pathological processes, from inflammatory dermatoses to type 2 diabetes and cancer. As such, identifying new drugs to suppress inflammation is an area of intense interest. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat inflammation. Traditional drug discovery, including structure-based drug design, have largely fallen short of satisfying this unmet need. With faster development times and reduced safety and pharmacokinetic uncertainty, drug repositioning – the process of finding new uses for existing drugs – is emerging as an alternative strategy to traditional drug design that promises an improved risk-reward trade-off. Using a zebrafish in vivo neutrophil migration assay, we undertook a drug repositioning screen to identify unknown anti-inflammatory activities for known drugs. By interrogating a library of 1280 approved drugs for their ability to suppress the recruitment of neutrophils to tail fin injury, we identified a number of drugs with significant anti-inflammatory activity that have not previously been characterized as general anti-inflammatories. Importantly, we reveal that the ten most potent repositioned drugs from our zebrafish screen displayed conserved anti-inflammatory activity in a mouse model of skin inflammation (atopic dermatitis). This study provides compelling evidence that exploiting the zebrafish as an in vivo drug repositioning platform holds promise as a strategy to reveal new anti-inflammatory activities for existing drugs. PMID:25038060

Targeting human pathogenic bacteria by siderophores: A proteomics review.

PubMed

Ferreira, Daniela; Seca, Ana M L; C G A, Diana; Silva, Artur M S

2016-08-11

Human bacterial infections are still a major public health problem throughout the world. Therefore it is fundamental to understand how pathogenic bacteria interact with their human host and to develop more advanced drugs or vaccines in response to the increasing bacterial resistance. Since iron is essential to bacterial survival and growth inside the host tissues, these microorganisms have developed highly efficient iron-acquisition systems; the most common one involves the secretion of iron chelators into the extracellular environment, known as siderophores, and the corresponding siderophore-membrane receptors or transporters responsible for the iron uptake. In the past few decades, several biochemical methods and genetic screens have been employed to track down and identify these iron-scavenging molecules. However, compared with the previous "static" approaches, proteomic identification is revealing far more molecules through full protein mapping and becoming more rapid and selective, leading the scientific and medical community to consider standardizing proteomic tools for clinical biomarker detection of bacterial infectious diseases. In this review, we focus on human pathogenic Gram-negative bacteria and discuss the importance of siderophores in their virulence and the available proteomic strategies to identify siderophore-related proteins and their expression level under different growth conditions. The promising use of siderophore antibiotics to overcome bacterial resistance and the future of proteomics in the routine clinical care are also mentioned. Proteomic strategies to identify siderophore-related proteins and their expression level can be helpful to control and/or find a cure of infectious deseases especially if related with multidrug resistance. Siderophores are low-molecular-weight compounds produced by bacteria which can become clinical biomarkers and/or antibiotics used mainly in "Trojan horse" type strategies. Due to the above mention we think that the promising use of siderophore to overcome bacterial resistance and the future of proteomics in the routine clinical care is a hot topic that should be discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Promising School-Based Strategies and Intervention Guidelines to Increase Physical Activity of Adolescents

ERIC Educational Resources Information Center

Pardo, Berta Murillo; Bengoechea, Enrique Garcia; Lanaspa, Eduardo Generelo; Bush, Paula L.; Casterad, Javier Zaragoza; Clemente, Jose A. Julian; Gonzalez, Luis Garcia

2013-01-01

This narrative review describes the available scientific evidence regarding promising school-based strategies to increase physical activity of adolescents. We conducted a literature search for studies published up to 2011, regarding adolescent physical activity intervention studies that resulted in increased physical activity (regardless of…

Community Capacity Building for Physical Activity Promotion among Older Adults—A Literature Review

PubMed Central

Ubert, Tobias; Forberger, Sarah; Gansefort, Dirk; Zeeb, Hajo; Brand, Tilman

2017-01-01

Community-based interventions to promote physical activity (PA) among older adults are of high interest in health promotion since they promise to be effective strategies to reach this population group. Community capacity building, that is, the local promotion of knowledge, skills, commitment, structures, and leadership, is among the recommended core strategies. However, little guidance is provided on how to achieve a high degree of community capacity. This study aims to identify practical strategies to enhance community capacities for PA promotion among older adults (50 years or older) and to evaluate their success. A literature review was conducted using scientific databases (PsycInfo and Web of Sciences) and grey literature (national and international project databases), and 14 studies (16 articles) were identified. Five groups of capacity building strategies emerged from the literature: (1) building community coalitions and networks, (2) training of professionals, (3) training of laypersons, (4) strengthening competence and awareness in the target population, and (5) allocation of financial resources. All studies used more than one strategy. Coalition building and strengthening competence and awareness were most frequently used. Feasibility and acceptability of the capacity building strategies were demonstrated. However, intervention effects on PA behavior and other relevant outcomes were inconsistent. The one study that systematically compared different capacity building approaches did not find any evidence for beneficial effects of intensified capacity building. More rigorous research evaluating the efficacy of specific strategies to enhance community capacities for PA promotion is needed. PMID:28902146

Community Capacity Building for Physical Activity Promotion among Older Adults-A Literature Review.

PubMed

Ubert, Tobias; Forberger, Sarah; Gansefort, Dirk; Zeeb, Hajo; Brand, Tilman

2017-09-13

Community-based interventions to promote physical activity (PA) among older adults are of high interest in health promotion since they promise to be effective strategies to reach this population group. Community capacity building, that is, the local promotion of knowledge, skills, commitment, structures, and leadership, is among the recommended core strategies. However, little guidance is provided on how to achieve a high degree of community capacity. This study aims to identify practical strategies to enhance community capacities for PA promotion among older adults (50 years or older) and to evaluate their success. A literature review was conducted using scientific databases (PsycInfo and Web of Sciences) and grey literature (national and international project databases), and 14 studies (16 articles) were identified. Five groups of capacity building strategies emerged from the literature: (1) building community coalitions and networks, (2) training of professionals, (3) training of laypersons, (4) strengthening competence and awareness in the target population, and (5) allocation of financial resources. All studies used more than one strategy. Coalition building and strengthening competence and awareness were most frequently used. Feasibility and acceptability of the capacity building strategies were demonstrated. However, intervention effects on PA behavior and other relevant outcomes were inconsistent. The one study that systematically compared different capacity building approaches did not find any evidence for beneficial effects of intensified capacity building. More rigorous research evaluating the efficacy of specific strategies to enhance community capacities for PA promotion is needed.

Single session real-time fMRI neurofeedback has a lasting impact on cognitive behavioral therapy strategies.

PubMed

MacDuffie, Katherine E; MacInnes, Jeff; Dickerson, Kathryn C; Eddington, Kari M; Strauman, Timothy J; Adcock, R Alison

2018-01-01

To benefit from cognitive behavioral therapy (CBT), individuals must not only learn new skills but also strategically implement them outside of session. Here, we tested a novel technique for personalizing CBT skills and facilitating their generalization to daily life. We hypothesized that showing participants the impact of specific CBT strategies on their own brain function using real-time functional magnetic imaging (rt-fMRI) neurofeedback would increase their metacognitive awareness, help them identify effective strategies, and motivate real-world use. In a within-subjects design, participants who had completed a clinical trial of a standardized course of CBT created a personal repertoire of negative autobiographical stimuli and mood regulation strategies. From each participant's repertoire, a set of experimental and control strategies were identified; only experimental strategies were practiced in the scanner. During the rt-fMRI neurofeedback session, participants used negative stimuli and strategies from their repertoire to manipulate activation in the anterior cingulate cortex, a region implicated in emotional distress. The primary outcome measures were changes in participant ratings of strategy difficulty, efficacy, and frequency of use. As predicted, ratings for unscanned control strategies were stable across observations, whereas ratings for experimental strategies changed after neurofeedback. At follow-up one month after the session, efficacy and frequency ratings for scanned strategies were predicted by neurofeedback during the rt-fMRI session. These results suggest that rt-fMRI neurofeedback created a salient and durable learning experience for patients, extending beyond the scan session to guide and motivate CBT skill use weeks later. This metacognitive approach to neurofeedback offers a promising model for increasing clinical benefits from cognitive behavioral therapy by personalizing skills and facilitating generalization.

Using "Omics" and Integrated Multi-Omics Approaches to Guide Probiotic Selection to Mitigate Chytridiomycosis and Other Emerging Infectious Diseases.

PubMed

Rebollar, Eria A; Antwis, Rachael E; Becker, Matthew H; Belden, Lisa K; Bletz, Molly C; Brucker, Robert M; Harrison, Xavier A; Hughey, Myra C; Kueneman, Jordan G; Loudon, Andrew H; McKenzie, Valerie; Medina, Daniel; Minbiole, Kevin P C; Rollins-Smith, Louise A; Walke, Jenifer B; Weiss, Sophie; Woodhams, Douglas C; Harris, Reid N

2016-01-01

Emerging infectious diseases in wildlife are responsible for massive population declines. In amphibians, chytridiomycosis caused by Batrachochytrium dendrobatidis, Bd, has severely affected many amphibian populations and species around the world. One promising management strategy is probiotic bioaugmentation of antifungal bacteria on amphibian skin. In vivo experimental trials using bioaugmentation strategies have had mixed results, and therefore a more informed strategy is needed to select successful probiotic candidates. Metagenomic, transcriptomic, and metabolomic methods, colloquially called "omics," are approaches that can better inform probiotic selection and optimize selection protocols. The integration of multiple omic data using bioinformatic and statistical tools and in silico models that link bacterial community structure with bacterial defensive function can allow the identification of species involved in pathogen inhibition. We recommend using 16S rRNA gene amplicon sequencing and methods such as indicator species analysis, the Kolmogorov-Smirnov Measure, and co-occurrence networks to identify bacteria that are associated with pathogen resistance in field surveys and experimental trials. In addition to 16S amplicon sequencing, we recommend approaches that give insight into symbiont function such as shotgun metagenomics, metatranscriptomics, or metabolomics to maximize the probability of finding effective probiotic candidates, which can then be isolated in culture and tested in persistence and clinical trials. An effective mitigation strategy to ameliorate chytridiomycosis and other emerging infectious diseases is necessary; the advancement of omic methods and the integration of multiple omic data provide a promising avenue toward conservation of imperiled species.

Identification of Multiple Novel Protein Biomarkers Shed by Human Serous Ovarian Tumors into the Blood of Immunocompromised Mice and Verified in Patient Sera

PubMed Central

Beer, Lynn A.; Wang, Huan; Tang, Hsin-Yao; Cao, Zhijun; Chang-Wong, Tony; Tanyi, Janos L.; Zhang, Rugang; Liu, Qin; Speicher, David W.

2013-01-01

The most cancer-specific biomarkers in blood are likely to be proteins shed directly by the tumor rather than less specific inflammatory or other host responses. The use of xenograft mouse models together with in-depth proteome analysis for identification of human proteins in the mouse blood is an under-utilized strategy that can clearly identify proteins shed by the tumor. In the current study, 268 human proteins shed into mouse blood from human OVCAR-3 serous tumors were identified based upon human vs. mouse species differences using a four-dimensional plasma proteome fractionation strategy. A multi-step prioritization and verification strategy was subsequently developed to efficiently select some of the most promising biomarkers from this large number of candidates. A key step was parallel analysis of human proteins detected in the tumor supernatant, because substantially greater sequence coverage for many of the human proteins initially detected in the xenograft mouse plasma confirmed assignments as tumor-derived human proteins. Verification of candidate biomarkers in patient sera was facilitated by in-depth, label-free quantitative comparisons of serum pools from patients with ovarian cancer and benign ovarian tumors. The only proteins that advanced to multiple reaction monitoring (MRM) assay development were those that exhibited increases in ovarian cancer patients compared with benign tumor controls. MRM assays were facilely developed for all 11 novel biomarker candidates selected by this process and analysis of larger pools of patient sera suggested that all 11 proteins are promising candidate biomarkers that should be further evaluated on individual patient blood samples. PMID:23544127

Mutagenic Azo Dyes, Rather Than Flame Retardants, Are the Predominant Brominated Compounds in House Dust.

PubMed

Peng, Hui; Saunders, David M V; Sun, Jianxian; Jones, Paul D; Wong, Chris K C; Liu, Hongling; Giesy, John P

2016-12-06

Characterization of toxicological profiles by use of traditional targeted strategies might underestimate the risk of environmental mixtures. Unbiased identification of prioritized compounds provides a promising strategy for meeting regulatory needs. In this study, untargeted screening of brominated compounds in house dust was conducted using a data-independent precursor isolation and characteristic fragment (DIPIC-Frag) approach, which used data-independent acquisition (DIA) and a chemometric strategy to detect peaks and align precursor ions. A total of 1008 brominated compound peaks were identified in 23 house dust samples. Precursor ions and formulas were identified for 738 (73%) of the brominated compounds. A correlation matrix was used to cluster brominated compounds; three large groups were found for the 140 high-abundance brominated compounds, and only 24 (17%) of these compounds were previously known flame retardants. The predominant class of unknown brominated compounds was predicted to consist of nitrogen-containing compounds. Following further validation by authentic standards, these compounds (56%) were determined to be novel brominated azo dyes. The mutagenicity of one major component was investigated, and mutagenicity was observed at environmentally relevant concentrations. Results of this study demonstrated the existence of numerous unknown brominated compounds in house dust, with mutagenic azo dyes unexpectedly being identified as the predominant compounds.

Multi-constituent cardiovascular pills (MCCP)--challenges and promises of population-based prophylactic drug therapy for prevention of heart attack.

PubMed

Jamieson, Michael J; Naghavi, Morteza

2007-01-01

Risk factors for atherosclerotic cardiovascular disease (CVD) are highly co-prevalent but poorly identified and treated. The Screening for Heart Attack Prevention and Education (SHAPE) Task Force from the Association for Eradication of Heart Attack (AEHA) has recently proposed a new strategy that recommends screening for subclinical atherosclerosis and implementing aggressive treatment of "vulnerable patients". The Task Force has also envisioned future developments that may shift mass screening strategies to mass prophylactic therapy. The "Polypill" concept, introduced by Wald and Law suggests a combination of statin, low-dose antihypertensives, aspirin and folic acid, in a single pill, taken prophylactically by high risk population can cut CVD event rates by as much as 80%. In this communication, we review the challenges and promises of such a strategy. "Polypill" is but one of an astronomical number of possible multiconstituent pills (MCCP). Attractive as the MCCP concept is, it lacks evidence from randomized controlled trials, and begs numerous questions about the credibility of the concept, the design and synthesis of such complex pills, pharmacokinetics, pharmacodynamics, bioequivalence, "class" vs. unique properties, interactions, evidence of clinical efficacy and safety, regulatory approval, post-marketing surveillance, prescription vs. over-the-counter use, responsibility for initiating and monitoring therapy, patient education, counterfeiting and importation, reimbursement, advertisement, patent protection, commercial viability, etc. If these issues are favorably addressed, MCCP stand to dramatically change the manner in which CVD is prevented particularly in developing societies. Notwithstanding, assuming low commercial interests, realizing the promises of MCCP will demand serious attention from national public health policymakers. The clinical and regulatory implications of population-based secondary prevention (which rely on a different evidence base, and in which entirely different risk-benefit and cost-effectiveness considerations apply) remain issues for active debate.

Defense Small Business Innovation Research Program (SBIR). Volume 2. Navy Abstracts of Phase 1 Awards 1992

DTIC Science & Technology

1992-01-01

The results of these studies will be used to identify the most promising strategies for minimizing or eliminating the sources of damage. MUDAWAR ...NAVY Topic#: 92-097 DARPA Topic#: 92-145 NOVA MANAGFMENT, INC. MUDAWAR THERMAL SYSTEM, INC. ARMY Topic#: 92-087 NAVY Topic#: 92-136 ARMY Topic#: 92-089...TECHNOLOGIES, INC. MUDAWAR THERMAL SYSTEM. INC. NAVY Topic#: 92-120 NAVY Topic#: 92-137 FOSTER-MILLER, INC. MOUNTAIN OPTECH, INC. MSNW, INC. NAVY Topic#: 92-138

Integrated strategy for identifying minor components in complex samples combining mass defect, diagnostic ions and neutral loss information based on ultra-performance liquid chromatography-high resolution mass spectrometry platform: Folium Artemisiae Argyi as a case study.

PubMed

Ren, Dabing; Ran, Lu; Yang, Chong; Xu, Meilin; Yi, Lunzhao

2018-05-18

Ultra-performance liquid chromatography coupled to high-resolution mass spectrometry (UPLC-HRMS) has been used as a powerful tool to profile chemicals in traditional Chinese medicines. However, identification of potentially bioactive compounds is still a challenging work because of the large amount of information contained in the raw UPLC-HRMS data. Especially the ubiquitous matrix interference makes it more difficult to characterize the minor components. Therefore, rapid recognition and efficient extraction of the corresponding parent ions is critically important for identifying the attractive compounds in complex samples. Herein, we propose an integrated filtering strategy to remove un-related or interference MS 1 ions from the raw UPLC-HRMS data, which helps to retain the MS features of the target components and expose the compounds of interest as effective as possible. The proposed strategy is based on the use of a combination of different filtering methods, including nitrogen rule, mass defect, and neutral loss/diagnostic fragment ions filtering. The strategy was validated by rapid screening and identification of 16 methoxylated flavonoids and 55 chlorogenic acids analogues from the raw UPLC-HRMS dataset of Folium Artemisiae Argyi. Particularly, successful detection of several minor components indicated that the integrated strategy has obvious advantages over individual filtering methods, and it can be used as a promising method for screening and identifying compounds from complex samples, such as herbal medicines. Copyright © 2018 Elsevier B.V. All rights reserved.

Promissory accounts of personalisation in the commercialisation of genomic knowledge.

PubMed

Arribas-Ayllon, Michael; Sarangi, Srikant; Clarke, Angus

2011-01-01

As part of personalised medicine emerging from the human genomics revolution, many websites now offer direct-to-consumer genetic testing. Here, we examine three personal genomics companies--Navigenics, deCODEme and 23andMe--each of which represents contrasting registers of 'personalisation'. We identify three distinctive registers in these websites: a paternalistic (medical) register; a translational (scientific) register and a democratic (consumerist) register. We explore in detail the rhetorical and discourse devices employed in these websites to assess how personalised healthcare is promised to the public. Promising information that will empower prevention of common complex diseases and ensure better quality of life is conflated with promising greater access to personal information. The presence and absence of scientific legitimacy is related to concerns about accuracy and validity on the one side, and fears of paternalism and elitism on the other. Nevertheless, a common strategy uniting these different styles of personalisation is consumer empowerment. Finally, we consider the tension between the drive of translational medicine to make human genomic research practically relevant, and the intrinsic uncertainties of scientific research and show how, in the commercial domain, future risks are transformed into discourses of promise by concealing these uncertainties.

How to reduce the incidence of contrast induced acute kidney injury after cardiac invasive procedures, a review and practical recommendations.

PubMed

de Bie, Mihály K; van Rees, Johannes B; Herzog, Charles A; Rabelink, Ton J; Schalij, Martin J; Jukema, J Wouter

2011-07-01

Contrast induced acute kidney injury is an important complication after cardiac (invasive) procedures and is associated with substantial morbidity and mortality. The aim of the current article is to provide a comprehensive overview of the current knowledge regarding contrast induced acute kidney injury. Current literature was reviewed and relevant articles were selected. Articles were identified through MEDLINE and Pubmed selecting articles, limited between 1980 and 2010. The pathophysiological process resulting in contrast induced acute kidney injury is not completely understood, nevertheless several mechanisms involved have been proposed. However, the risk factors for contrast induced acute kidney injury and its timing are well known, making it amenable for preventive strategies. In the past decade various preventive strategies have been investigated with different results. Currently, only adequate hydration, with saline, is uniformly accepted as a beneficial prophylactic strategy. Furthermore promising results have also been reported for several other prophylactic strategies. These results, however, need to be confirmed in future trials.

Building synthetic gene circuits from combinatorial libraries: screening and selection strategies.

PubMed

Schaerli, Yolanda; Isalan, Mark

2013-07-01

The promise of wide-ranging biotechnology applications inspires synthetic biologists to design novel genetic circuits. However, building such circuits rationally is still not straightforward and often involves painstaking trial-and-error. Mimicking the process of natural selection can help us to bridge the gap between our incomplete understanding of nature's design rules and our desire to build functional networks. By adopting the powerful method of directed evolution, which is usually applied to protein engineering, functional networks can be obtained through screening or selecting from randomised combinatorial libraries. This review first highlights the practical options to introduce combinatorial diversity into gene circuits and then examines strategies for identifying the potentially rare library members with desired functions, either by screening or selection.

Efficient Testing Combining Design of Experiment and Learn-to-Fly Strategies

NASA Technical Reports Server (NTRS)

Murphy, Patrick C.; Brandon, Jay M.

2017-01-01

Rapid modeling and efficient testing methods are important in a number of aerospace applications. In this study efficient testing strategies were evaluated in a wind tunnel test environment and combined to suggest a promising approach for both ground-based and flight-based experiments. Benefits of using Design of Experiment techniques, well established in scientific, military, and manufacturing applications are evaluated in combination with newly developing methods for global nonlinear modeling. The nonlinear modeling methods, referred to as Learn-to-Fly methods, utilize fuzzy logic and multivariate orthogonal function techniques that have been successfully demonstrated in flight test. The blended approach presented has a focus on experiment design and identifies a sequential testing process with clearly defined completion metrics that produce increased testing efficiency.

ACTIVE SURVEILLANCE FOR PAPILLARY THYROID MICROCARCINOMA: NEW CHALLENGES AND OPPORTUNITIES FOR THE HEALTH CARE SYSTEM

PubMed Central

Haser, Grace C.; Tuttle, R. Michael; Su, Henry K.; Alon, Eran E.; Bergman, Donald; Bernet, Victor; Brett, Elise; Cobin, Rhoda; Dewey, Eliza H.; Doherty, Gerard; Dos Reis, Laura L.; Harris, Jeffrey; Klopper, Joshua; Lee, Stephanie L.; Levine, Robert A.; Lepore, Stephen J.; Likhterov, Ilya; Lupo, Mark A.; Machac, Josef; Mechanick, Jeffrey I.; Mehra, Saral; Milas, Mira; Orloff, Lisa A.; Randolph, Gregory; Revenson, Tracey A.; Roberts, Katherine J.; Ross, Douglas S.; Rowe, Meghan E.; Smallridge, Robert C.; Terris, David; Tufano, Ralph P.; Urken, Mark L.

2017-01-01

Objective The dramatic increase in papillary thyroid carcinoma (PTC) is primarily a result of early diagnosis of small cancers. Active surveillance is a promising management strategy for papillary thyroid microcarcinomas (PTMCs). However, as this management strategy gains traction in the U.S., it is imperative that patients and clinicians be properly educated, patients be followed for life, and appropriate tools be identified to implement the strategy. Methods We review previous active surveillance studies and the parameters used to identify patients who are good candidates for active surveillance. We also review some of the challenges to implementing active surveillance protocols in the U.S. and discuss how these might be addressed. Results Trials of active surveillance support nonsurgical management as a viable and safe management strategy. However, numerous challenges exist, including the need for adherence to protocols, education of patients and physicians, and awareness of the impact of this strategy on patient psychology and quality of life. The Thyroid Cancer Care Collaborative (TCCC) is a portable record keeping system that can manage a mobile patient population undergoing active surveillance. Conclusion With proper patient selection, organization, and patient support, active surveillance has the potential to be a long-term management strategy for select patients with PTMC. In order to address the challenges and opportunities for this approach to be successfully implemented in the U.S., it will be necessary to consider psychological and quality of life, cultural differences, and the patient’s clinical status. PMID:26799628

Successful Organizational Strategies to Sustain Use of A-CHESS: A Mobile Intervention for Individuals With Alcohol Use Disorders.

PubMed

Ford, James H; Alagoz, Esra; Dinauer, Susan; Johnson, Kimberly A; Pe-Romashko, Klaren; Gustafson, David H

2015-08-18

Mobile health (mHealth) services are growing in importance in health care research with the advancement of wireless networks, tablets, and mobile phone technologies. These technologies offer a wide range of applications that cover the spectrum of health care delivery. Although preliminary experiments in mHealth demonstrate promising results, more robust real-world evidence is needed for widespread adoption and sustainment of these technologies. Our aim was to identify the problems/challenges associated with sustained use of an mHealth addiction recovery support app and to determine strategies used by agencies that successfully sustained client use of A-CHESS. Qualitative inquiry assessed staff perceptions about organizational attributes and strategies associated with sustained use of the mobile app, A-CHESS. A total of 73 interviews of clinicians and administrators were conducted. The initial interviews (n=36) occurred at the implementation of A-CHESS. Follow-up interviews (n=37) occurred approximately 12 and 24 months later. A coding scheme was developed and Multiuser NVivo was used to manage and analyze the blinded interview data. Successful strategies used by treatment providers to sustain A-CHESS included (1) strong leadership support, (2) use of client feedback reports to follow up on non-engaged clients, (3) identify passionate staff and incorporate A-CHESS discussions in weekly meetings, (4) develop A-CHESS guidelines related to client use, (5) establish internal work groups to engage clients, and (6) establish a financial strategy to sustain A-CHESS use. The study also identified attributes of A-CHESS that enhanced as well as inhibited its sustainability. Mobile apps can play an important role in health care delivery. However, providers will need to develop strategies for engaging both staff and patients in ongoing use of the apps. They will also need to rework business processes to accommodate the changes in communication frequency and style, learn to use app data for decision making, and identify financing mechanisms for supporting these changes.

Potential determinants of deductible uptake in health insurance: How to increase uptake in The Netherlands?

PubMed

van Winssen, K P M; van Kleef, R C; van de Ven, W P M M

2016-12-01

In health insurance, voluntary deductibles are offered to the insured in return for a premium rebate. Previous research has shown that 11 % of the Dutch insured opted for a voluntary deductible (VD) in health insurance in 2014, while the highest VD level was financially profitable for almost 50 % of the population in retrospect. To explain this discrepancy, this paper identifies and discusses six potential determinants of the decision to opt for a VD from the behavioral economic literature: loss aversion, risk attitude, ambiguity aversion, debt aversion, omission bias, and liquidity constraints. Based on these determinants, five potential strategies are proposed to increase the number of insured opting for a VD. Presenting the VD as the default option and providing transparent information regarding the VD are the two most promising strategies. If, as a result of these strategies, more insured would opt for a VD, moral hazard would be reduced.

Recruiting Teachers Online: Marketing Strategies and Information Dissemination Practices of UK-Based Agencies

ERIC Educational Resources Information Center

de Villiers, Rian; Books, Sue

2009-01-01

A review of the websites of 43 UK-based agencies that are recruiting teachers in South Africa and other countries finds that important information about what to expect often is missing. An analysis of the marketing strategies shows that agencies overall are promising schools thorough vetting of candidates and low fees, are promising prospective…

Hawaii energy strategy project 3: Renewable energy resource assessment and development program

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

NONE

1995-11-01

RLA Consulting (RLA) has been retained by the State of Hawaii Department of Business, Economic Development and Tourism (DBEDT) to conduct a Renewable Energy Resource Assessment and Development Program. This three-phase program is part of the Hawaii Energy Strategy (HES), which is a multi-faceted program intended to produce an integrated energy strategy for the State of Hawaii. The purpose of Phase 1 of the project, Development of a Renewable Energy Resource Assessment Plan, is to better define the most promising potential renewable energy projects and to establish the most suitable locations for project development in the state. In order tomore » accomplish this goal, RLA has identified constraints and requirements for renewable energy projects from six different renewable energy resources: wind, solar, biomass, hydro, wave, and ocean thermal. These criteria were applied to areas with sufficient resource for commercial development and the results of Phase 1 are lists of projects with the most promising development potential for each of the technologies under consideration. Consideration of geothermal energy was added to this investigation under a separate contract with DBEDT. In addition to the project lists, a monitoring plan was developed with recommended locations and a data collection methodology for obtaining additional wind and solar data. This report summarizes the results of Phase 1. 11 figs., 22 tabs.« less

Petri net siphon analysis and graph theoretic measures for identifying combination therapies in cancer.

PubMed

Behinaein, Behnam; Rudie, Karen; Sangrar, Waheed

2016-10-03

Epidermal Growth Factor Receptor (EGFR) signaling to the Ras-MAPK pathway is implicated in the development and progression of cancer and is a major focus of targeted combination therapies. Physiochemical models have been used for identifying and testing the signal-inhibiting potential of targeted therapies, however, their application to larger multi-pathway networks is limited by the availability of experimentally-determined rate and concentration parameters. An alternate strategy for identifying and evaluating drug-targetable nodes is proposed. A physiochemical model of EGFR-Ras-MAPK signaling is implemented and calibrated to experimental data. Essential topological features of the model are converted into a Petri net and nodes that behave as siphons-a structural property of Petri nets-are identified. Siphons represent potential drug-targets since they are unrecoverable if their values fall below a threshold. Centrality measures are then used to prioritize siphons identified as candidate drug-targets. Single and multiple drug-target combinations are identified which correspond to clinically relevant drug targets and exhibit inhibition synergy in physiochemical simulations of EGF-induced EGFR-Ras-MAPK signaling. Taken together, these studies suggest that siphons and centrality analyses are a promising computational strategy to identify and rank drug-targetable nodes in larger networks as they do not require knowledge of the dynamics of the system, but rely solely on topology.

Breast tumor segmentation in DCE-MRI using fully convolutional networks with an application in radiogenomics

NASA Astrophysics Data System (ADS)

Zhang, Jun; Saha, Ashirbani; Zhu, Zhe; Mazurowski, Maciej A.

2018-02-01

Breast tumor segmentation based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) remains an active as well as a challenging problem. Previous studies often rely on manual annotation for tumor regions, which is not only time-consuming but also error-prone. Recent studies have shown high promise of deep learning-based methods in various segmentation problems. However, these methods are usually faced with the challenge of limited number (e.g., tens or hundreds) of medical images for training, leading to sub-optimal segmentation performance. Also, previous methods cannot efficiently deal with prevalent class-imbalance problems in tumor segmentation, where the number of voxels in tumor regions is much lower than that in the background area. To address these issues, in this study, we propose a mask-guided hierarchical learning (MHL) framework for breast tumor segmentation via fully convolutional networks (FCN). Our strategy is first decomposing the original difficult problem into several sub-problems and then solving these relatively simpler sub-problems in a hierarchical manner. To precisely identify locations of tumors that underwent a biopsy, we further propose an FCN model to detect two landmarks defined on nipples. Finally, based on both segmentation probability maps and our identified landmarks, we proposed to select biopsied tumors from all detected tumors via a tumor selection strategy using the pathology location. We validate our MHL method using data for 272 patients, and achieve a mean Dice similarity coefficient (DSC) of 0.72 in breast tumor segmentation. Finally, in a radiogenomic analysis, we show that a previously developed image features show a comparable performance for identifying luminal A subtype when applied to the automatic segmentation and a semi-manual segmentation demonstrating a high promise for fully automated radiogenomic analysis in breast cancer.

Quorum Quenching Agents: Resources for Antivirulence Therapy

PubMed Central

Tang, Kaihao; Zhang, Xiao-Hua

2014-01-01

The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ) agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy. PMID:24886865

Screening phage display libraries for organ-specific vascular immunotargeting in vivo

PubMed Central

Valadon, Philippe; Garnett, Jeff D.; Testa, Jacqueline E.; Bauerle, Marc; Oh, Phil; Schnitzer, Jan E.

2006-01-01

The molecular diversity of the luminal endothelial cell surface arising in vivo from local variations in genetic expression and tissue microenvironment may create opportunities for achieving targeted molecular imaging and therapies. Here, we describe a strategy to identify probes and their cognate antigens for targeting vascular endothelia of specific organs in vivo. We differentially screen phage libraries to select organ-targeting antibodies by using luminal endothelial cell plasma membranes isolated directly from tissue and highly enriched in natively expressed proteins exposed to the bloodstream. To obviate liver uptake of intravenously injected phage, we convert the phage-displayed antibodies into scFv-Fc fusion proteins, which then are able to rapidly target select organ(s) in vivo as visualized directly by γ-scintigraphic whole-body imaging. Mass spectrometry helps identify the antigen targets. This comprehensive strategy provides new promise for harnessing the power of phage display for mapping vascular endothelia natively in tissue and for achieving vascular targeting of specific tissues in vivo. PMID:16384919

Manipulating regulatory T cells: a promising strategy to treat autoimmunity.

PubMed

Zhang, Dunfang; Tu, Eric; Kasagi, Shimpei; Zanvit, Peter; Chen, Qianming; Chen, WanJun

2015-01-01

CD4(+)CD25(+)Foxp3(+)regulatory T cells (Treg cells) are extremely important in maintaining immune tolerance. Manipulation of Treg cells, especially autoantigen-specific Treg cells is a promising approach for treatments of autoimmune disease since Treg cells may provide the advantage of antigen specificity without overall immune suppression. However, the clinical application of Treg cells has long been limited due to low numbers of Treg cells and the difficulty in identifying their antigen specificity. In this review, we summarize studies that demonstrate regression of autoimmune diseases using Treg cells as therapeutics. We also discuss approaches to generate polyclonal and autoantigen-specific Treg cells in vitro and in vivo. We also discuss our recent study that describes a novel approach of generating autoantigen-specific Treg cells in vivo and restoring immune tolerance by two steps apoptosis-antigen therapy.

Why Do Promising Therapies Stall in Development and How Can We Move Them Forward?

PubMed

Wegner, Craig D; Goodwin, Andrew; Cook, Jon C; Allamneni, Krishna; Sohn, Jane; McVean, Maralee

There are many reasons that molecules fail to progress to market and various principles of risk-benefit decisions that can help drive the molecule through development. This symposium included discussions on global strategies involved in pushing promising molecules to market, what to do when a molecule stalls in its progress to market, and options for rescuing the molecule and pushing it forward again. Innovative partnerships that bring stalled drugs back into clinical development were also addressed. A regulatory perspective on common reasons for a molecule to fail in its forward progress was presented. In addition, situations arise when a third-party advisory committee can provide input to help overcome issues identified by a regulatory agency. Using examples from the private and public domain, presentations centered on how to repurpose a molecule and when more science is needed.

The Business, Ethics, and Quality Cases for Consumer Engagement in Nursing

PubMed Central

Hassmiller, Susan; Bilazarian, Ani

2018-01-01

OBJECTIVE The aims of this study were to illustrate the quality, safety, cost-effectiveness, and ethics of consumer engagement initiatives and identify promising practices and leadership strategies used by nursing leaders. METHODS A literature review was performed with supplementary interviews conducted with 25 key nursing informants including nursing executives and chief nursing officers at acute care hospitals, community health centers, policy institutions, and quality and safety organizations. A narrative synthesis approach was used to identify and compare existing measures of consumer engagement and compassionate care in acute care settings. One-hour semistructured interviews were performed, and information was gathered by notes and audio recordings. RESULTS Consumer engagement activities focusing on compassionate patient and provider interactions involving patients and family as partners on the care team are associated with increases in treatment savings and patient safety in terms of length of stay and reduced medication errors. Engagement initiatives support employee health and reduce compassion fatigue. CONCLUSION Findings illustrate the impact of patients and family engagement in decision making and promising organizational practices that reinforce engagement. PMID:29470381

First-principles investigations of ionic conduction in Li and Na borohydrides

NASA Astrophysics Data System (ADS)

Varley, Joel; Heo, Tae-Wook; Ray, Keith; Bonev, Stanimir; Wood, Brandon

Recent experimental studies have identified a family of alkali borohydride materials that exhibit superionic transition temperatures approaching room temperature and ionic conductivities exceeding 0.1 S/cm-1, making them highly promising solid electrolytes for next-generation batteries. Despite the rapid advances in improving the superionic conductivity in these materials, an understanding of the exact mechanisms driving the transport remains unknown. Here we use ab initio molecular dynamics calculations to address this issue by characterizing the diffusivity of the Li and Na species in a representative set of closoborane ionic conductors. We investigate both the Na and Li-containing borohydrides with icosahedral (B12H12) and double-capped square antiprism (B10H10) anion species and discuss the trends in ionic conductivity as a function of stoichiometry and the incorporation of various dopants. Our results support the borohydrides as a subset of a larger family of very promising solid electrolytes and identify strategies to improving the conductivity in these materials. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

What Works in Community-Based Interventions Promoting Physical Activity and Healthy Eating? A Review of Reviews

PubMed Central

Brand, Tilman; Pischke, Claudia R.; Steenbock, Berit; Schoenbach, Johanna; Poettgen, Saskia; Samkange-Zeeb, Florence; Zeeb, Hajo

2014-01-01

Chronic diseases, such as type II diabetes, are on the rise worldwide. There is consistent evidence that physical activity and healthy eating are important lifestyle factors which affect the risk for chronic diseases. Community-based interventions are of particular public health interest as they reach target groups in their natural living environment and may thus achieve high population-level impacts. We conducted a systematic literature search to assess the effectiveness of community-based interventions to promote physical activity and healthy eating. Specifically, we searched for promising intervention strategies in this setting. We narratively summarized the results of 18 systematic reviews. Among children and adolescents, we found moderate evidence for effects on weight change in primary school-aged children for interventions containing a school component. The evidence for interventions aimed at general adult populations was inconclusive. Self-monitoring, group-based components, and motivational signs to encourage stair use were identified as promising strategies to increase physical activity. Among adults at risk for type II diabetes, evidence was found for beneficial effects on weight change and diabetes incidence. However, interventions for this group were not integrated in more comprehensive community-based approaches. PMID:24886756

Knowledge translation in job development: strategies for involving families.

PubMed

Hall, Allison; Bose, Jennifer; Winsor, Jean; Migliore, Alberto

2014-09-01

Although United States employment policies have increased support for people with disabilities working in community settings, the unemployment rate for this population remains very high, particularly for people with intellectual or developmental disabilities. Research shows that job developers (direct support professionals who assist people with disabilities to secure, maintain, and advance in employment) are critical to achieving quality employment outcomes. However, the extent to which job developers use practices that are considered promising in their field (such as engaging families) is not well known. This brief report summarizes findings from a qualitative study about the extent to which job developers use the recommended promising practices when working with individuals and family members. Qualitative analysis identified the following themes among job developers: factors affecting family involvement, perceptions of family involvement, and the influence of expectation on strategies. The field of job development faces a challenge common to many professions: translating research on best practices to those who need this knowledge the most and can use it to greatest effect. Future research should address how community rehabilitation providers (CRPs) communicate about and instill best practices, including effective family engagement, within their organizations. © 2013 John Wiley & Sons Ltd.

Discovery of Novel ROCK1 Inhibitors via Integrated Virtual Screening Strategy and Bioassays

PubMed Central

Shen, Mingyun; Tian, Sheng; Pan, Peichen; Sun, Huiyong; Li, Dan; Li, Youyong; Zhou, Hefeng; Li, Chuwen; Lee, Simon Ming-Yuen; Hou, Tingjun

2015-01-01

Rho-associated kinases (ROCKs) have been regarded as promising drug targets for the treatment of cardiovascular diseases, nervous system diseases and cancers. In this study, a novel integrated virtual screening protocol by combining molecular docking and pharmacophore mapping based on multiple ROCK1 crystal structures was utilized to screen the ChemBridge database for discovering potential inhibitors of ROCK1. Among the 38 tested compounds, seven of them exhibited significant inhibitory activities of ROCK1 (IC50 < 10 μM) and the most potent one (compound TS-f22) with the novel scaffold of 4-Phenyl-1H-pyrrolo [2,3-b] pyridine had an IC50 of 480 nM. Then, the structure-activity relationships of 41 analogues of TS-f22 were examined. Two potent inhibitors were proven effective in inhibiting the phosphorylation of the downstream target in the ROCK signaling pathway in vitro and protecting atorvastatin-induced cerebral hemorrhage in vivo. The high hit rate (28.95%) suggested that the integrated virtual screening strategy was quite reliable and could be used as a powerful tool for identifying promising active compounds for targets of interest. PMID:26568382

Discovery of Novel ROCK1 Inhibitors via Integrated Virtual Screening Strategy and Bioassays.

PubMed

Shen, Mingyun; Tian, Sheng; Pan, Peichen; Sun, Huiyong; Li, Dan; Li, Youyong; Zhou, Hefeng; Li, Chuwen; Lee, Simon Ming-Yuen; Hou, Tingjun

2015-11-16

Rho-associated kinases (ROCKs) have been regarded as promising drug targets for the treatment of cardiovascular diseases, nervous system diseases and cancers. In this study, a novel integrated virtual screening protocol by combining molecular docking and pharmacophore mapping based on multiple ROCK1 crystal structures was utilized to screen the ChemBridge database for discovering potential inhibitors of ROCK1. Among the 38 tested compounds, seven of them exhibited significant inhibitory activities of ROCK1 (IC50 < 10 μM) and the most potent one (compound TS-f22) with the novel scaffold of 4-Phenyl-1H-pyrrolo [2,3-b] pyridine had an IC50 of 480 nM. Then, the structure-activity relationships of 41 analogues of TS-f22 were examined. Two potent inhibitors were proven effective in inhibiting the phosphorylation of the downstream target in the ROCK signaling pathway in vitro and protecting atorvastatin-induced cerebral hemorrhage in vivo. The high hit rate (28.95%) suggested that the integrated virtual screening strategy was quite reliable and could be used as a powerful tool for identifying promising active compounds for targets of interest.

Antimicrobial Potential of Bacteria Associated with Marine Sea Slugs from North Sulawesi, Indonesia.

PubMed

Böhringer, Nils; Fisch, Katja M; Schillo, Dorothee; Bara, Robert; Hertzer, Cora; Grein, Fabian; Eisenbarth, Jan-Hendrik; Kaligis, Fontje; Schneider, Tanja; Wägele, Heike; König, Gabriele M; Schäberle, Till F

2017-01-01

Nudibranchia, marine soft-bodied organisms, developed, due to the absence of a protective shell, different strategies to protect themselves against putative predators and fouling organisms. One strategy is to use chemical weapons to distract predators, as well as pathogenic microorganisms. Hence, these gastropods take advantage of the incorporation of chemical molecules. Thereby the original source of these natural products varies; it might be the food source, de novo synthesis from the sea slug, or biosynthesis by associated bacteria. These bioactive molecules applied by the slugs can become important drug leads for future medicinal drugs. To test the potential of the associated bacteria, the latter were isolated from their hosts, brought into culture and extracts were prepared and tested for antimicrobial activities. From 49 isolated bacterial strains 35 showed antibiotic activity. The most promising extracts were chosen for further testing against relevant pathogens. In that way three strains showing activity against methicillin resistant Staphylococcus aureus and one strain with activity against enterohemorrhagic Escherichia coli , respectively, were identified. The obtained results indicate that the sea slug associated microbiome is a promising source for bacterial strains, which hold the potential for the biotechnological production of antibiotics.

In silico strategies for the selection of chelating compounds with potential application in metal-promoted neurodegenerative diseases

NASA Astrophysics Data System (ADS)

Rodríguez-Rodríguez, Cristina; Rimola, Albert; Alí-Torres, Jorge; Sodupe, Mariona; González-Duarte, Pilar

2011-01-01

The development of new strategies to find commercial molecules with promising biochemical features is a main target in the field of biomedicine chemistry. In this work we present an in silico-based protocol that allows identifying commercial compounds with suitable metal coordinating and pharmacokinetic properties to act as metal-ion chelators in metal-promoted neurodegenerative diseases (MpND). Selection of the chelating ligands is done by combining quantum chemical calculations with the search of commercial compounds on different databases via virtual screening. Starting from different designed molecular frameworks, which mainly constitute the binding site, the virtual screening on databases facilitates the identification of different commercial molecules that enclose such scaffolds and, by imposing a set of chemical and pharmacokinetic filters, obey some drug-like requirements mandatory to deal with MpND. The quantum mechanical calculations are useful to gauge the chelating properties of the selected candidate molecules by determining the structure of metal complexes and evaluating their stability constants. With the proposed strategy, commercial compounds containing N and S donor atoms in the binding sites and capable to cross the BBB have been identified and their chelating properties analyzed.

Dual targeting of MDM2 and BCL2 as a therapeutic strategy in neuroblastoma.

PubMed

Van Goethem, Alan; Yigit, Nurten; Moreno-Smith, Myrthala; Vasudevan, Sanjeev A; Barbieri, Eveline; Speleman, Frank; Shohet, Jason; Vandesompele, Jo; Van Maerken, Tom

2017-08-22

Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner. The venetoclax/idasanutlin combination was consistently found to be highly synergistic in a diverse panel of neuroblastoma cell lines, including cells with high MCL1 expression levels. A more pronounced induction of apoptosis was found to underlie the synergistic interaction, as evidenced by caspase-3/7 and cleaved PARP measurements. Mice carrying orthotopic xenografts of neuroblastoma cells treated with both idasanutlin and venetoclax had drastically lower tumor weights than mice treated with either treatment alone. In conclusion, these data strongly support the further evaluation of dual BCL2/MDM2 targeting as a therapeutic strategy in neuroblastoma.

Opportunities to protect instream flows in Colorado and Wyoming

USGS Publications Warehouse

Trembly, Terrence L.

1987-01-01

This document combines the efforts of several individuals, agencies, and organizations toward a common objective: the identification, description, and preliminary evaluation of promising opportunities for protecting instream uses of water under existing laws in Colorado and Wyoming. This report is intended for the use of State and Federal planning and management personnel who need an overview of potential opportunities for preserving instream flows. It is not intended to replace or challenge the advice of agency counsel, nor it is written to provide legal advice. Instead, it is designed as a guide for the person trying to find his or her way among sometimes bewildering State statues and administrative practices. This report is not, and should not be taken as, official policy or prediction of future actions by any agency. It is simply a summary of some potential opportunities for protecting instream uses. Toward these objectives, the U.S. Fish and Wildlife Service, through its Water Resources Analysis Project, contracted in 1977 with Richard Dewsnup and Dallin Jensen to identify available strategies under State and Federal laws, interstate compacts, and water quality laws. A second firm, Enviro Control, Inc., was contracted to evaluate the most promising strategies. Two of the resulting documents were Instream Flow Strategies for Colorado and Instream Flow Strategies for Wyoming, which have been revised, updated, and combined in this report. Discussion of instream flow programs ad opportunities for each State--Colorado and Wyoming-- are written so that each report can be read independently, with minimal cross referencing from one State report to another.

The challenges of implementing advanced access for residents in family medicine in Quebec. Do promising strategies exist?

PubMed

Abou Malham, Sabina; Touati, Nassera; Maillet, Lara; Breton, Mylaine

2018-12-01

The advanced access (AA) model is a highly recommended innovation to improve timely access to primary healthcare. Despite that many studies have shown positive impacts for healthcare professionals, and for patients, implementing this model in clinics with a teaching mission for family medicine residents poses specific challenges. To identify these challenges within these clinics, as well as potential strategies to address them. The authors adopted a qualitative multiple case study design, collected data in 2016 using semi-structured interviews (N = 40) with healthcare professionals and clerical staff in four family medicine units in Quebec, and performed a thematic analysis. They validated results through a discussion workshop, involving many family physicians and residents practicing in different regions Results: Five challenges emerged from the data: 1) choosing, organizing residents' patient; 2) managing and balancing residents' appointment schedules; 3) balancing timely access with relational continuity; 4) understanding the AA model; 5) establishing collaborative practices with other health professionals. Several promising strategies were suggested to address these challenges, including clearly defining residents' patient panels; adopting a team-based care approach; incorporating the model into academic curriculum and clinical training; proactive and ongoing education of health professionals, residents, and patients; involving residents in the change process and in adjustment strategies. To meet the challenges of implementing AA, decision-makers should consider exposing residents to AA during academic training and clinical internships, involving them in team work on arrival, engaging them as key actors in the implementation and in intra- and inter-professional collaborative models.

The challenges of implementing advanced access for residents in family medicine in Quebec. Do promising strategies exist?

PubMed Central

Abou Malham, Sabina; Touati, Nassera; Maillet, Lara; Breton, Mylaine

2018-01-01

ABSTRACT Background: The advanced access (AA) model is a highly recommended innovation to improve timely access to primary healthcare. Despite that many studies have shown positive impacts for healthcare professionals, and for patients, implementing this model in clinics with a teaching mission for family medicine residents poses specific challenges. Objective: To identify these challenges within these clinics, as well as potential strategies to address them. Design: The authors adopted a qualitative multiple case study design, collected data in 2016 using semi-structured interviews (N = 40) with healthcare professionals and clerical staff in four family medicine units in Quebec, and performed a thematic analysis. They validated results through a discussion workshop, involving many family physicians and residents practicing in different regions Results: Five challenges emerged from the data: 1) choosing, organizing residents’ patient; 2) managing and balancing residents’ appointment schedules; 3) balancing timely access with relational continuity; 4) understanding the AA model; 5) establishing collaborative practices with other health professionals. Several promising strategies were suggested to address these challenges, including clearly defining residents’ patient panels; adopting a team-based care approach; incorporating the model into academic curriculum and clinical training; proactive and ongoing education of health professionals, residents, and patients; involving residents in the change process and in adjustment strategies. Conclusions: To meet the challenges of implementing AA, decision-makers should consider exposing residents to AA during academic training and clinical internships, involving them in team work on arrival, engaging them as key actors in the implementation and in intra- and inter-professional collaborative models. PMID:29464984

Creating an enabling environment for adolescent sexual and reproductive health: a framework and promising approaches.

PubMed

Svanemyr, Joar; Amin, Avni; Robles, Omar J; Greene, Margaret E

2015-01-01

This article provides a conceptual framework and points out the key elements for creating enabling environments for adolescent sexual and reproductive health (ASRH). An ecological framework is applied to organize the key elements of enabling environments for ASRH. At the individual level, strategies that are being implemented and seem promising are those that empower girls, build their individual assets, and create safe spaces. At the relationship level, strategies that are being implemented and seem promising include efforts to build parental support and communication as well as peer support networks. At the community level, strategies to engage men and boys and the wider community to transform gender and other social norms are being tested and may hold promise. Finally, at the broadest societal level, efforts to promote laws and policies that protect and promote human rights and address societal awareness about ASRH issues, including through mass media approaches, need to be considered. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Getting men in the room: perceptions of effective strategies to initiate men's involvement in gender-based violence prevention in a global sample.

PubMed

Casey, Erin A; Leek, Cliff; Tolman, Richard M; Allen, Christopher T; Carlson, Juliana M

2017-09-01

As engaging men in gender-based violence prevention efforts becomes an increasingly institutionalised component of gender equity work globally, clarity is needed about the strategies that best initiate male-identified individuals' involvement in these efforts. The purpose of this study was to examine the perceived relevance and effectiveness of men's engagement strategies from the perspective of men around the world who have organised or attended gender-based violence prevention events. Participants responded to an online survey (available in English, French and Spanish) and rated the effectiveness of 15 discrete engagement strategies derived from earlier qualitative work. Participants also provided suggestions regarding strategies in open-ended comments. Listed strategies cut across the social ecological spectrum and represented both venues in which to reach men, and the content of violence prevention messaging. Results suggest that all strategies, on average, were perceived as effective across regions of the world, with strategies that tailor messaging to topics of particular concern to men (such as fatherhood and healthy relationships) rated most highly. Open-ended comments also surfaced tensions, particularly related to the role of a gender analysis in initial men's engagement efforts. Findings suggest the promise of cross-regional adaptation and information sharing regarding successful approaches to initiating men's anti-violence involvement.

Expanding syphilis testing: a scoping review of syphilis testing interventions among key populations.

PubMed

Ong, Jason J; Fu, Hongyun; Smith, M Kumi; Tucker, Joseph D

2018-05-01

Syphilis is an important sexually transmitted infection (STI). Despite inexpensive and effective treatment, few key populations receive syphilis testing. Innovative strategies are needed to increase syphilis testing among key populations. Areas covered: This scoping review focused on strategies to increase syphilis testing in key populations (men who have sex with men (MSM), sex workers, people who use drugs, transgender people, and incarcerated individuals). Expert commentary: We identified many promising syphilis testing strategies, particularly among MSM. These innovations are separated into diagnostic, clinic-based, and non-clinic based strategies. In terms of diagnostics, self-testing, dried blood spots, and point-of-care testing can decentralize syphilis testing. Effective syphilis self-testing pilots suggest the need for further attention and research. In terms of clinic-based strategies, modifying default clinical procedures can nudge physicians to more frequently recommend syphilis testing. In terms of non-clinic based strategies, venue-based screening (e.g. in correctional facilities, drug rehabilitation centres) and mobile testing units have been successfully implemented in a variety of settings. Integration of syphilis with HIV testing may facilitate implementation in settings where individuals have increased sexual risk. There is a strong need for further syphilis testing research and programs.

Meta-Analysis in Genome-Wide Association Datasets: Strategies and Application in Parkinson Disease

PubMed Central

Evangelou, Evangelos; Maraganore, Demetrius M.; Ioannidis, John P.A.

2007-01-01

Background Genome-wide association studies hold substantial promise for identifying common genetic variants that regulate susceptibility to complex diseases. However, for the detection of small genetic effects, single studies may be underpowered. Power may be improved by combining genome-wide datasets with meta-analytic techniques. Methodology/Principal Findings Both single and two-stage genome-wide data may be combined and there are several possible strategies. In the two-stage framework, we considered the options of (1) enhancement of replication data and (2) enhancement of first-stage data, and then, we also considered (3) joint meta-analyses including all first-stage and second-stage data. These strategies were examined empirically using data from two genome-wide association studies (three datasets) on Parkinson disease. In the three strategies, we derived 12, 5, and 49 single nucleotide polymorphisms that show significant associations at conventional levels of statistical significance. None of these remained significant after conservative adjustment for the number of performed analyses in each strategy. However, some may warrant further consideration: 6 SNPs were identified with at least 2 of the 3 strategies and 3 SNPs [rs1000291 on chromosome 3, rs2241743 on chromosome 4 and rs3018626 on chromosome 11] were identified with all 3 strategies and had no or minimal between-dataset heterogeneity (I2 = 0, 0 and 15%, respectively). Analyses were primarily limited by the suboptimal overlap of tested polymorphisms across different datasets (e.g., only 31,192 shared polymorphisms between the two tier 1 datasets). Conclusions/Significance Meta-analysis may be used to improve the power and examine the between-dataset heterogeneity of genome-wide association studies. Prospective designs may be most efficient, if they try to maximize the overlap of genotyping platforms and anticipate the combination of data across many genome-wide association studies. PMID:17332845

A cost-effectiveness analysis evaluating endoscopic surveillance for gastric cancer for populations with low to intermediate risk.

PubMed

Zhou, Hui Jun; Dan, Yock Young; Naidoo, Nasheen; Li, Shu Chuen; Yeoh, Khay Guan

2013-01-01

Gastric cancer (GC) surveillance based on oesophagogastroduodenoscopy (OGD) appears to be a promising strategy for GC prevention. By evaluating the cost-effectiveness of endoscopic surveillance in Singaporean Chinese, this study aimed to inform the implementation of such a program in a population with a low to intermediate GC risk. USING A REFERENCE STRATEGY OF NO OGD INTERVENTION, WE EVALUATED FOUR STRATEGIES: 2-yearly OGD surveillance, annual OGD surveillance, 2-yearly OGD screening and 2-yearly screening plus annual surveillance in Singaporean Chinese aged 50-69 years. From a perspective of the healthcare system, Markov models were built to simulate the life experience of the target population. The models projected discounted lifetime costs ($), quality adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER) indicating the cost-effectiveness of each strategy against a Singapore willingness-to-pay of $46,200/QALY. Deterministic and probabilistic sensitivity analyses were used to identify the influential variables and their associated thresholds, and to quantify the influence of parameter uncertainties respectively. With an ICER of $44,098/QALY, the annual OGD surveillance was the optimal strategy while the 2-yearly surveillance was the most cost-effective strategy (ICER = $25,949/QALY). The screening-based strategies were either extendedly dominated or cost-ineffective. The cost-effectiveness heterogeneity of the four strategies was observed across age-gender subgroups. Eight influential parameters were identified each with their specific thresholds to define the choice of optimal strategy. Accounting for the model uncertainties, the probability that the annual surveillance is the optimal strategy in Singapore was 44.5%. Endoscopic surveillance is potentially cost-effective in the prevention of GC for populations at low to intermediate risk. Regarding program implementation, a detailed analysis of influential factors and their associated thresholds is necessary. Multiple strategies should be considered in order to recommend the right strategy for the right population.

Financial barriers and pricing strategies related to participation in sports activities: the perceptions of people of low income.

PubMed

Steenhuis, Ingrid H M; Nooy, Steffie B C; Moes, Machiel J G; Schuit, Albertine J

2009-11-01

Physical activity levels in most affluent countries are low and many people do not meet the current recommendations. Particularly for people with a low income, economic strategies seem promising to stimulate taking part in sports activities. This study investigated the importance of economic restraints for taking part in sports activities as well as perceptions of low-income people toward different pricing interventions. A qualitative study was conducted, using semistructured, individual interviews with 27 low-income men and women. The framework approach was used to analyze the transcripts of the interviews. The respondents considered finances to be an important barrier for participating in sports activities, together with some individual barriers. Promising pricing strategies are a discount on the subscription to the fitness or sports club, a 1 month free trial, and free entrance to the swimming pool once a week. Pricing strategies may be a promising intervention to increase physical activity levels of low-income people. However, this study indicates that this should be coupled with an intervention directed at individual barriers. Some pricing strategies will be used and appreciated more by low-income people than other pricing strategies. In addition, pricing strategies should be tailored to individual needs and preferences.

STEM CELL IMAGING: FROM BENCH TO BEDSIDE

PubMed Central

Nguyen, Patricia K.; Riegler, Johannes; Wu, Joseph C.

2014-01-01

Although cellular therapies hold great promise for the treatment of human disease, results from several initial clinical trials have not shown a level of efficacy required for their use as a first line therapy. Here we discuss how in vivo molecular imaging has helped identify barriers to clinical translation and potential strategies that may contribute to successful transplantation and improved outcomes, with a focus on cardiovascular and neurological diseases. We conclude with a perspective on the future role of molecular imaging in defining safety and efficacy for stem cell clinical implementation. PMID:24702995

Advances in autism genetics: on the threshold of a new neurobiology

PubMed Central

Abrahams, Brett S.; Geschwind, Daniel H.

2009-01-01

Autism is a heterogeneous syndrome defined by impairments in three core domains: social interaction, language and range of interests. Recent work has led to the identification of several autism susceptibility genes and an increased appreciation of the contribution of de novo and inherited copy number variation. Promising strategies are also being applied to identify common genetic risk variants. Systems biology approaches, including array-based expression profiling, are poised to provide additional insights into this group of disorders, in which heterogeneity, both genetic and phenotypic, is emerging as a dominant theme. PMID:18414403

Bringing a Network-Oriented Approach to Domestic Violence Services: A Focus Group Exploration of Promising Practices.

PubMed

Goodman, Lisa A; Banyard, Victoria; Woulfe, Julie; Ash, Sarah; Mattern, Grace

2016-01-01

Despite powerful evidence that informal social support contributes to survivors' safety and well-being, mainstream domestic violence (DV) programs have not developed comprehensive models for helping isolated survivors re-engage with these networks. Although many advocates use network-oriented strategies informally, they often do so without resources, funding, or training. This qualitative focus group study explored advocates' use and perceptions of network-oriented strategies. Advocates working in a range of DV programs across one state described the importance of network-oriented work and articulated its five dimensions, including helping survivors build their capacity to form healthy relationships, identify helpful and harmful network members, re-engage with existing networks, develop new relationships, and respond more effectively to network members. © The Author(s) 2015.

Combination Pharmacotherapies for Stimulant Use Disorder: A Review of Clinical Findings and Recommendations for Future Research

PubMed Central

Stoops, William W.; Rush, Craig R.

2014-01-01

Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. Innovative strategies are necessary to develop successful pharmacotherapies for stimulant use disorders. This manuscript reviews human laboratory studies and clinical trials to determine whether one such strategy, use of combination pharmacotherapies, holds promise. The extant literature shows that combination pharmacotherapy produced results that were better than placebo treatment, especially with medications shown to have efficacy as monotherapies. However, many studies did not compare individual constituents to the combination treatment, making it impossible to determine whether combination treatment is more effective than monotherapy. Future research should systematically compare combined treatments with individual agents using medications showing some efficacy when tested alone. PMID:24716825

Knockdown of genes in the Toll pathway reveals new lethal RNA interference targets for insect pest control.

PubMed

Bingsohn, L; Knorr, E; Billion, A; Narva, K E; Vilcinskas, A

2017-02-01

RNA interference (RNAi) is a promising alternative strategy for ecologically friendly pest management. However, the identification of RNAi candidate genes is challenging owing to the absence of laboratory strains and the seasonality of most pest species. Tribolium castaneum is a well-established model, with a strong and robust RNAi response, which can be used as a high-throughput screening platform to identify potential RNAi target genes. Recently, the cactus gene was identified as a sensitive RNAi target for pest control. To explore whether the spectrum of promising RNAi targets can be expanded beyond those found by random large-scale screening, to encompass others identified using targeted knowledge-based approaches, we constructed a Cactus interaction network. We tested nine genes in this network and found that the delivery of double-stranded RNA corresponding to fusilli and cactin showed lethal effects. The silencing of cactin resulted in 100% lethality at every developmental stage from the larva to the adult. The knockdown of pelle, Dorsal-related immunity factor and short gastrulation reduced or even prevented egg hatching in the next generation. The combination of such targets with lethal and parental RNAi effects can now be tested against different pest species in field studies. © 2016 The Royal Entomological Society.

Design and Control of Integrated Systems for Hydrogen Production and Power Generation

NASA Astrophysics Data System (ADS)

Georgis, Dimitrios

Growing concerns on CO2 emissions have led to the development of highly efficient power plants. Options for increased energy efficiencies include alternative energy conversion pathways, energy integration and process intensification. Solid oxide fuel cells (SOFC) constitute a promising alternative for power generation since they convert the chemical energy electrochemically directly to electricity. Their high operating temperature shows potential for energy integration with energy intensive units (e.g. steam reforming reactors). Although energy integration is an essential tool for increased efficiencies, it leads to highly complex process schemes with rich dynamic behavior, which are challenging to control. Furthermore, the use of process intensification for increased energy efficiency imposes an additional control challenge. This dissertation identifies and proposes solutions on design, operational and control challenges of integrated systems for hydrogen production and power generation. Initially, a study on energy integrated SOFC systems is presented. Design alternatives are identified, control strategies are proposed for each alternative and their validity is evaluated under different operational scenarios. The operational range of the proposed control strategies is also analyzed. Next, thermal management of water gas shift membrane reactors, which are a typical application of process intensification, is considered. Design and operational objectives are identified and a control strategy is proposed employing advanced control algorithms. The performance of the proposed control strategy is evaluated and compared with classical control strategies. Finally SOFC systems for combined heat and power applications are considered. Multiple recycle loops are placed to increase design flexibility. Different operational objectives are identified and a nonlinear optimization problem is formulated. Optimal designs are obtained and their features are discussed and compared. The results of the dissertation provide a deeper understanding on the design, operational and control challenges of the above systems and can potentially guide further commercialization efforts. In addition to this, the results can be generalized and used for applications from the transportation and residential sector to large--scale power plants.

Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

PubMed

Sibille, Kimberly T; Bartsch, Felix; Reddy, Divya; Fillingim, Roger B; Keil, Andreas

2016-03-01

Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promotion of adaptive, treatment-responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain's response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimization of learning and positive central nervous system adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research, however, has identified a wide spectrum of methods that can be used to "reopen" and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, that are noninvasive, inexpensive to administer, implementable in numerous settings, and might be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, and evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain is presented. Neuroplastic changes are a defining feature of chronic pain and a complicating factor in treatment. Noninvasive strategies to optimize the brain's response to treatment interventions might improve learning and memory, increase the positive adaptability of the central nervous system, and enhance treatment outcomes. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Neurocognitive Allied Phenotypes for Schizophrenia and Bipolar Disorder

PubMed Central

Hill, S. Kristian; Harris, Margret S. H.; Herbener, Ellen S.; Pavuluri, Mani; Sweeney, John A.

2008-01-01

Psychiatric disorders are genetically complex and represent the end product of multiple biological and social factors. Links between genes and disorder-related abnormalities can be effectively captured via assessment of phenotypes that are both associated with genetic effects and potentially contributory to behavioral abnormalities. Identifying intermediate or allied phenotypes as a strategy for clarifying genetic contributions to disorders has been successful in other areas of medicine and is a promising strategy for identifying susceptibility genes in complex psychiatric disorders. There is growing evidence that schizophrenia and bipolar disorder, rather than being wholly distinct disorders, share genetic risk at several loci. Further, there is growing evidence of similarity in the pattern of cognitive and neurobiological deficits in these groups, which may be the result of the effects of these common genetic factors. This review was undertaken to identify patterns of performance on neurocognitive and affective tasks across probands with schizophrenia and bipolar disorder as well as unaffected family members, which warrant further investigation as potential intermediate trait markers. Available evidence indicates that measures of attention regulation, working memory, episodic memory, and emotion processing offer potential for identifying shared and illness-specific allied neurocognitive phenotypes for schizophrenia and bipolar disorder. However, very few studies have evaluated neurocognitive dimensions in bipolar probands or their unaffected relatives, and much work in this area is needed. PMID:18448479

Anti-infectious drug repurposing using an integrated chemical genomics and structural systems biology approach.

PubMed

Ng, Clara; Hauptman, Ruth; Zhang, Yinliang; Bourne, Philip E; Xie, Lei

2014-01-01

The emergence of multi-drug and extensive drug resistance of microbes to antibiotics poses a great threat to human health. Although drug repurposing is a promising solution for accelerating the drug development process, its application to anti-infectious drug discovery is limited by the scope of existing phenotype-, ligand-, or target-based methods. In this paper we introduce a new computational strategy to determine the genome-wide molecular targets of bioactive compounds in both human and bacterial genomes. Our method is based on the use of a novel algorithm, ligand Enrichment of Network Topological Similarity (ligENTS), to map the chemical universe to its global pharmacological space. ligENTS outperforms the state-of-the-art algorithms in identifying novel drug-target relationships. Furthermore, we integrate ligENTS with our structural systems biology platform to identify drug repurposing opportunities via target similarity profiling. Using this integrated strategy, we have identified novel P. falciparum targets of drug-like active compounds from the Malaria Box, and suggest that a number of approved drugs may be active against malaria. This study demonstrates the potential of an integrative chemical genomics and structural systems biology approach to drug repurposing.

Novel therapeutic strategies in myelodysplastic syndromes: do molecular genetics help?

PubMed

Chung, Stephen S

2016-03-01

Many studies over the past decade have together identified genes that are recurrently mutated in the myelodysplastic syndromes (MDS). We will summarize how this information has informed our understanding of disease pathogenesis and behavior, with an emphasis on how this information may inform therapeutic strategies. Genomic sequencing techniques have allowed for the identification of many recurrently mutated genes in MDS, with the most common mutations being found in epigenetic modifiers and components of the splicing machinery. Although many mutations are associated with clinical outcomes and disease phenotypes, at the current time they add relatively little to already robust clinical prognostic algorithms. However, as molecular genetic data are accumulated in larger numbers of patients, it is likely that the clinical significance of co-occurring mutations and less common mutations will come to light. Finally, mutated genes may identify biologically distinct subgroups of MDS that may benefit from novel therapies, and a subset of these genes may themselves serve as therapeutic targets. Advances in our knowledge of the molecular genetics of MDS have significantly improved our understanding of disease biology and promise to improve tools for clinical decision-making and identify new therapies for patients.

Cross-platform method for identifying candidate network biomarkers for prostate cancer.

PubMed

Jin, G; Zhou, X; Cui, K; Zhang, X-S; Chen, L; Wong, S T C

2009-11-01

Discovering biomarkers using mass spectrometry (MS) and microarray expression profiles is a promising strategy in molecular diagnosis. Here, the authors proposed a new pipeline for biomarker discovery that integrates disease information for proteins and genes, expression profiles in both genomic and proteomic levels, and protein-protein interactions (PPIs) to discover high confidence network biomarkers. Using this pipeline, a total of 474 molecules (genes and proteins) related to prostate cancer were identified and a prostate-cancer-related network (PCRN) was derived from the integrative information. Thus, a set of candidate network biomarkers were identified from multiple expression profiles composed by eight microarray datasets and one proteomics dataset. The network biomarkers with PPIs can accurately distinguish the prostate patients from the normal ones, which potentially provide more reliable hits of biomarker candidates than conventional biomarker discovery methods.

Using NLP to identify cancer cases in imaging reports drawn from radiology information systems.

PubMed

Patrick, Jon; Asgari, Pooyan; Li, Min; Nguyen, Dung

2013-01-01

A Natural Language processing (NLP) classifier has been developed for the Victorian and NSW Cancer Registries with the purpose of automatically identifying cancer reports from imaging services, transmitting them to the Registries and then extracting pertinent cancer information. Large scale trials conducted on over 40,000 reports show the sensitivity for identifying reportable cancer reports is above 98% with a specificity above 96%. Detection of tumour stream, report purpose, and a variety of extracted content is generally above 90% specificity. The differences between report layout and authoring strategies across imaging services appear to require different classifiers to retain this high level of accuracy. Linkage of the imaging data with existing registry records (hospital and pathology reports) to derive stage and recurrence of cancer has commenced and shown very promising results.

Long-Term Use and Perceived Benefits of Goal-Oriented Attentional Self-Regulation Training in Chronic Brain Injury.

PubMed

Loya, Fred; Novakovic-Agopian, Tatjana; Binder, Deborah; Rossi, Annemarie; Rome, Scott; Murphy, Michelle; Chen, Anthony J-W

2017-01-01

Primary Objective. To investigate the long-term use and perceived benefit(s) of strategies included in Goal-Oriented Attentional Self-Regulation (GOALS) training (Novakovic-Agopian et al., 2011) by individuals with acquired brain injury (ABI) and chronic executive dysfunction. Research Design. Longitudinal follow-up of training. Methods and Procedures. Sixteen participants with chronic ABI participated in structured telephone interviews 20 months (range 11 to 31 months) following completion of GOALS training. Participants responded to questions regarding the range of strategies they continued to utilize, perceived benefit(s) of strategy use, situations in which strategy use was found helpful, and functional changes attributed to training. Results. Nearly all participants (94%) reported continued use of at least one trained strategy in their daily lives, with 75% of participants also reporting improved functioning resulting from training. However, there was considerable variability with respect to the specific strategies individuals found helpful as well as the perceived impact of training on overall functioning. Conclusions. GOALS training shows promising long-term benefits for individuals in the chronic phase of brain injury. Identifying individual- and injury-level factors that account for variability in continued strategy use and the perceived long-term benefits of training will help with ongoing intervention development.

Long-Term Use and Perceived Benefits of Goal-Oriented Attentional Self-Regulation Training in Chronic Brain Injury

PubMed Central

Novakovic-Agopian, Tatjana; Binder, Deborah; Rossi, Annemarie; Rome, Scott; Murphy, Michelle; Chen, Anthony J.-W.

2017-01-01

Primary Objective. To investigate the long-term use and perceived benefit(s) of strategies included in Goal-Oriented Attentional Self-Regulation (GOALS) training (Novakovic-Agopian et al., 2011) by individuals with acquired brain injury (ABI) and chronic executive dysfunction. Research Design. Longitudinal follow-up of training. Methods and Procedures. Sixteen participants with chronic ABI participated in structured telephone interviews 20 months (range 11 to 31 months) following completion of GOALS training. Participants responded to questions regarding the range of strategies they continued to utilize, perceived benefit(s) of strategy use, situations in which strategy use was found helpful, and functional changes attributed to training. Results. Nearly all participants (94%) reported continued use of at least one trained strategy in their daily lives, with 75% of participants also reporting improved functioning resulting from training. However, there was considerable variability with respect to the specific strategies individuals found helpful as well as the perceived impact of training on overall functioning. Conclusions. GOALS training shows promising long-term benefits for individuals in the chronic phase of brain injury. Identifying individual- and injury-level factors that account for variability in continued strategy use and the perceived long-term benefits of training will help with ongoing intervention development. PMID:28265472

Aptamer-Based Analysis: A Promising Alternative for Food Safety Control

PubMed Central

Amaya-González, Sonia; de-los-Santos-Álvarez, Noemí; Miranda-Ordieres, Arturo J.; Lobo-Castañón, Maria Jesús

2013-01-01

Ensuring food safety is nowadays a top priority of authorities and professional players in the food supply chain. One of the key challenges to determine the safety of food and guarantee a high level of consumer protection is the availability of fast, sensitive and reliable analytical methods to identify specific hazards associated to food before they become a health problem. The limitations of existing methods have encouraged the development of new technologies, among them biosensors. Success in biosensor design depends largely on the development of novel receptors with enhanced affinity to the target, while being stable and economical. Aptamers fulfill these characteristics, and thus have surfaced as promising alternatives to natural receptors. This Review describes analytical strategies developed so far using aptamers for the control of pathogens, allergens, adulterants, toxins and other forbidden contaminants to ensure food safety. The main progresses to date are presented, highlighting potential prospects for the future. PMID:24287543

Sea thermal power; A survey study for the Arab coastal waters

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

Abdell-AAL, H.K.; Khan, M.M.

1990-01-01

One of the promising types of renewable energy resource that has potential applications in the Arab world is proposed and described in this article. Known as ocean thermal energy conversion (OTEC), its feasibility is investigated for the Red Sea and the Arabian Gulf/Gulf of Oman. Data on thermal gradients are surveyed, collected, and reported. Promising parameters have been identified for some specific locations along these coastal waters. The proposed system can serve the dual purpose of providing electric power and desalinated water, which is needed by the Arab world. Construction strategies for the OTEC systems are introduced. Building plant-ship formore » utilizing the generated power in the production of hydrogen is recommended. Thus energy could be transported as LH{sub 2} (liquid hydrogen), MeOH (methanol), or NH{sub 3} (ammonia) for end-use consumption or export.« less

Sequencing Structural Variants in Cancer for Precision Therapeutics.

PubMed

Macintyre, Geoff; Ylstra, Bauke; Brenton, James D

2016-09-01

The identification of mutations that guide therapy selection for patients with cancer is now routine in many clinical centres. The majority of assays used for solid tumour profiling use DNA sequencing to interrogate somatic point mutations because they are relatively easy to identify and interpret. Many cancers, however, including high-grade serous ovarian, oesophageal, and small-cell lung cancer, are driven by somatic structural variants that are not measured by these assays. Therefore, there is currently an unmet need for clinical assays that can cheaply and rapidly profile structural variants in solid tumours. In this review we survey the landscape of 'actionable' structural variants in cancer and identify promising detection strategies based on massively-parallel sequencing. Copyright © 2016 Elsevier Ltd. All rights reserved.

In silico profiling of Escherichia coli and Saccharomyces cerevisiae as terpenoid factories

PubMed Central

2013-01-01

Background Heterologous microbial production of rare plant terpenoids of medicinal or industrial interest is attracting more and more attention but terpenoid yields are still low. Escherichia coli and Saccharomyces cerevisiae are the most widely used heterologous hosts; a direct comparison of both hosts based on experimental data is difficult though. Hence, the terpenoid pathways of E. coli (via 1-deoxy-D-xylulose 5-phosphate, DXP) and S. cerevisiae (via mevalonate, MVA), the impact of the respective hosts metabolism as well as the impact of different carbon sources were compared in silico by means of elementary mode analysis. The focus was set on the yield of isopentenyl diphosphate (IPP), the general terpenoid precursor, to identify new metabolic engineering strategies for an enhanced terpenoid yield. Results Starting from the respective precursor metabolites of the terpenoid pathways (pyruvate and glyceraldehyde-3-phosphate for the DXP pathway and acetyl-CoA for the MVA pathway) and considering only carbon stoichiometry, the two terpenoid pathways are identical with respect to carbon yield. However, with glucose as substrate, the MVA pathway has a lower potential to supply terpenoids in high yields than the DXP pathway if the formation of the required precursors is taken into account, due to the carbon loss in the formation of acetyl-CoA. This maximum yield is further reduced in both hosts when the required energy and reduction equivalents are considered. Moreover, the choice of carbon source (glucose, xylose, ethanol or glycerol) has an effect on terpenoid yield with non-fermentable carbon sources being more promising. Both hosts have deficiencies in energy and redox equivalents for high yield terpenoid production leading to new overexpression strategies (heterologous enzymes/pathways) for an enhanced terpenoid yield. Finally, several knockout strategies are identified using constrained minimal cut sets enforcing a coupling of growth to a terpenoid yield which is higher than any yield published in scientific literature so far. Conclusions This study provides for the first time a comprehensive and detailed in silico comparison of the most prominent heterologous hosts E. coli and S. cerevisiae as terpenoid factories giving an overview on several promising metabolic engineering strategies paving the way for an enhanced terpenoid yield. PMID:24059635

Landscape review of current HIV 'kick and kill' cure research - some kicking, not enough killing.

PubMed

Thorlund, Kristian; Horwitz, Marc S; Fife, Brian T; Lester, Richard; Cameron, D William

2017-08-29

Current antiretroviral therapy (ART) used to treat human immunodeficiency virus (HIV) patients is life-long because it only suppresses de novo infections. Recent efforts to eliminate HIV have tested the ability of a number of agents to reactivate ('Kick') the well-known latent reservoir. This approach is rooted in the assumption that once these cells are reactivated the host's immune system itself will eliminate ('Kill') the virus. While many agents have been shown to reactivate large quantities of the latent reservoir, the impact on the size of the latent reservoir has been negligible. This suggests that the immune system is not sufficient to eliminate reactivated reservoirs. Thus, there is a need for more emphasis on 'kill' strategies in HIV cure research, and how these might work in combination with current or future kick strategies. We conducted a landscape review of HIV 'cure' clinical trials using 'kick and kill' approaches. We identified and reviewed current available clinical trial results in human participants as well as ongoing and planned clinical trials. We dichotomized trials by whether they did not include or include a 'kill' agent. We extracted potential reasons why the 'kill' is missing from current 'kick and kill' strategies. We subsequently summarized and reviewed current 'kill' strategies have entered the phase of clinical trial testing in human participants and highlighted those with the greatest promise. The identified 'kick' trials only showed promise on surrogate measures activating latent T-cells, but did not show any positive effects on clinical 'cure' measures. Of the 'kill' agents currently being tested in clinical trials, early results have shown small but meaningful proportions of participants remaining off ART for several months with broadly neutralizing antibodies, as well as agents for regulating immune cell responses. A similar result was also recently observed in a trial combining a conventional 'kick' with a vaccine immune booster ('kill'). While an understanding of the efficacy of each individual component is crucial, no single 'kick' or 'kill' agent is likely to be a fully effective cure. Rather, the solution is likely found in a combination of multiple 'kick and kill' interventions.

An integrated high resolution mass spectrometric data acquisition method for rapid screening of saponins in Panax notoginseng (Sanqi).

PubMed

Lai, Chang-Jiang-Sheng; Tan, Ting; Zeng, Su-Ling; Qi, Lian-Wen; Liu, Xin-Guang; Dong, Xin; Li, Ping; Liu, E-Hu

2015-05-10

The aim of this study was to develop a convenient method without pretreatments for nontarget discovery of interested compounds. The segment and exposure strategy, coupled with two mass spectrometer data acquisition methods was firstly proposed for screening the saponins in extract of Panax notoginseng (Sanqi) via high-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC-QTOF/MS). By gradually removing certain major or moderate interference compounds, the developed segment and exposure strategy could significantly improve the detection efficiency for trace compounds. Moreover, the newly developed five-point screening approach based on a modified mass defect filter strategy and the visual isotopic ion technique was verified to be efficient and reliable in picking out the interested precursor ions. In total, 234 ginsenosides including 67 potential new ones were characterized or tentatively identified from the extract of Sanqi. Particularly, some unusual compounds containing the branched glycosyl group or new substituted acyl groups were firstly reported. The proposed integrated strategy held a strong promise for analyses of the complex mixtures. Copyright © 2015 Elsevier B.V. All rights reserved.

Scoping review of adherence promotion theories in pelvic floor muscle training - 2011 ICS state-of-the-science seminar research paper i of iv.

PubMed

McClurg, Doreen; Frawley, Helena; Hay-Smith, Jean; Dean, Sarah; Chen, Shu-Yueh; Chiarelli, Pauline; Mair, Frances; Dumoulin, Chantale

2015-09-01

This paper, the first of four emanating from the International Continence Society's 2011 State-of-the-Science Seminar on pelvic-floor-muscle training (PFMT) adherence, aimed to summarize the literature on theoretical models to promote PFMT adherence, as identified in the research, or suggested by the seminar's expert panel, and recommends future directions for clinical practice and research. Existing literature on theories of health behavior were identified through a conventional subject search of electronic databases, reference-list checking, and input from the expert panel. A core eligibility criterion was that the study included a theoretical model to underpin adherence strategies used in an intervention to promote PFM training/exercise. A brief critique of 12 theoretical models/theories is provided and, were appropriate, their use in PFMT adherence strategies identified or examples of possible uses in future studies outlined. A better theoretical-based understanding of interventions to promote PFMT adherence through changes in health behaviors is required. The results of this scoping review and expert opinions identified several promising models. Future research should explicitly map the theories behind interventions that are thought to improve adherence in various populations (e.g., perinatal women to prevent or lessen urinary incontinence). In addition, identified behavioral theories applied to PFMT require a process whereby their impact can be evaluated. © 2015 Wiley Periodicals, Inc.

CMS Innovation Center Health Care Innovation Awards

PubMed Central

Berry, Sandra H.; Concannon, Thomas W.; Morganti, Kristy Gonzalez; Auerbach, David I.; Beckett, Megan K.; Chen, Peggy G.; Farley, Donna O.; Han, Bing; Harris, Katherine M.; Jones, Spencer S.; Liu, Hangsheng; Lovejoy, Susan L.; Marsh, Terry; Martsolf, Grant R.; Nelson, Christopher; Okeke, Edward N.; Pearson, Marjorie L.; Pillemer, Francesca; Sorbero, Melony E.; Towe, Vivian; Weinick, Robin M.

2013-01-01

Abstract The Center for Medicare and Medicaid Innovation within the Centers for Medicare & Medicaid Services (CMS) has funded 108 Health Care Innovation Awards, funded through the Affordable Care Act, for applicants who proposed compelling new models of service delivery or payment improvements that promise to deliver better health, better health care, and lower costs through improved quality of care for Medicare, Medicaid, and Children's Health Insurance Program enrollees. CMS is also interested in learning how new models would affect subpopulations of beneficiaries (e.g., those eligible for Medicare and Medicaid and complex patients) who have unique characteristics or health care needs that could be related to poor outcomes. In addition, the initiative seeks to identify new models of workforce development and deployment, as well as models that can be rapidly deployed and have the promise of sustainability. This article describes a strategy for evaluating the results. The goal for the evaluation design process is to create standardized approaches for answering key questions that can be customized to similar groups of awardees and that allow for rapid and comparable assessment across awardees. The evaluation plan envisions that data collection and analysis will be carried out on three levels: at the level of the individual awardee, at the level of the awardee grouping, and as a summary evaluation that includes all awardees. Key dimensions for the evaluation framework include implementation effectiveness, program effectiveness, workforce issues, impact on priority populations, and context. The ultimate goal is to identify strategies that can be employed widely to lower cost while improving care. PMID:28083297

A Systematic Review of Promising Strategies of Faith-Based Cancer Education and Lifestyle Interventions Among Racial/Ethnic Minority Groups.

PubMed

Hou, Su-I; Cao, Xian

2017-09-13

Church-based interventions have been used to reach racial/ethnic minorities. In order to develop effective programs, we conducted a comprehensive systematic review of faith-based cancer prevention studies (2005~2016) to examine characteristics and promising strategies. Combination terms "church or faith-based or religion," "intervention or program," and "cancer education or lifestyle" were used in searching the five major databases: CINAHL; ERIC; Health Technology Assessments; MEDLINE; and PsycInfo. A total of 20 studies met study criteria. CDC's Community Guide was used to analyze and review group interventions. Analyses were organized by two racial groups: African American (AA) and Latino/Hispanic American groups. Results showed most studies reviewed focused on breast cancer alone or in combination with other cancers. Studies of Latino/Hispanic groups targeted more on uninsured, Medicare, or Medicaid individuals, whereas AA studies generally did not include specific insurance criteria. The sample sizes of the AA studies were generally larger. The majority of these studies reviewed used pre-post, posttest only with control group, or quasi-experience designs. The Health Belief Model was the most commonly used theory in both groups. Community-based participatory research and empowerment/ecological frameworks were also used frequently in the Latino/Hispanic studies. Small media and group education were the top two most popular intervention strategies in both groups. Although one-on-one strategy was used in some Latino studies, neither group used reducing client out-of-pocket costs strategy. Client reminders could also be used more in both groups as well. Current review showed church-based cancer education programs were effective in changing knowledge, but not always screening utilization. Results show faith-based cancer educational interventions are promising. To maximize intervention impact, future studies might consider using stronger study designs, incorporating a variety of proven effective strategies, including those frequently used evidence-based strategies, as well as exploring promising strategies among specific target groups.

State health care financing strategies for children with intellectual and developmental disabilities.

PubMed

Bachman, Sara S; Comeau, Margaret; Tobias, Carol; Allen, Deborah; Epstein, Susan; Jantz, Kathryn; Honberg, Lynda

2012-06-01

We provide the first descriptive summary of selected programs developed to help expand the scope of coverage, mitigate family financial hardship, and provide health and support services that children with intellectual and developmental disabilities need to maximize their functional status and quality of life. State financing initiatives were identified through interviews with family advocacy, Title V, and Medicaid organizational representatives. Results showed that states use myriad strategies to pay for care and maximize supports, including benefits counseling, consumer- and family-directed care, flexible funding, mandated benefits, Medicaid buy-in programs, and Tax Equity and Fiscal Responsibility Act of 1982 funding. Although health reform may reduce variation among states, its impact on families of children with intellectual and developmental disabilities is not yet clear. As health reform is implemented, state strategies to ameliorate financial hardship among families of children with intellectual and developmental disabilities show promise for immediate use. However, further analysis and evaluation are required to understand their impact on family and child well-being.

Effectiveness of international environmental regimes: Existing knowledge, cutting-edge themes, and research strategies

PubMed Central

Young, Oran R.

2011-01-01

International environmental regimes—especially those regimes articulated in multilateral environmental agreements—have been a subject of intense interest within the scientific community over the last three decades. However, there are substantial differences of opinion regarding the effectiveness of these governance systems or the degree to which they are successful in solving the problems leading to their creation. This article provides a critical review of the literature on this topic. It extracts and summarizes what is known about the effectiveness of environmental regimes in the form of a series of general and specific propositions. It identifies promising topics for consideration in the next phase of research in this field. Additionally, it comments on the research strategies available to pursue this line of analysis. The general conclusions are that international environmental regimes can and do make a difference, although often in conjunction with a number of other factors, and that a strategy of using a number of tools combined can help to improve understanding of the determinants of success. PMID:22143795

Results and Indicators for Children: An Analysis to Inform Discussions about Promise Neighborhoods

ERIC Educational Resources Information Center

Moore, Kristin Anderson; Murphey, David; Emig, Carol; Hamilton, Kathleen; Hadley, Alena; Sidorowicz, Katie

2009-01-01

President Obama has proposed creation of up to 20 "Promise Neighborhoods" in communities experiencing poverty, crime, and low student achievement. Promise Neighborhoods would engage children and parents within a defined geographic area in a multifaceted strategy to meet several goals: good physical and mental health for every child, enrollment in…

Credit with Education: A Promising Title II Microfinance Strategy--Supporting Integrated Food Security and Nutrition Programs To Improve Health and Well-Being of Women and Children). Food and Nutrition Technical Assistance.

ERIC Educational Resources Information Center

Dunford, Christopher; Denman, Vicki

This paper introduces the reader to microfinance integrated with health and nutrition education as a promising strategy for Title II practitioners. The paper provides an overview of how microfinance, particularly village banking, can contribute to the food-security objectives of Title II. It describes a variant of village banking, called…

Successful Organizational Strategies to Sustain Use of A-CHESS: A Mobile Intervention for Individuals With Alcohol Use Disorders

PubMed Central

Alagoz, Esra; Dinauer, Susan; Johnson, Kimberly A; Pe-Romashko, Klaren; Gustafson, David H

2015-01-01

Background Mobile health (mHealth) services are growing in importance in health care research with the advancement of wireless networks, tablets, and mobile phone technologies. These technologies offer a wide range of applications that cover the spectrum of health care delivery. Although preliminary experiments in mHealth demonstrate promising results, more robust real-world evidence is needed for widespread adoption and sustainment of these technologies. Objective Our aim was to identify the problems/challenges associated with sustained use of an mHealth addiction recovery support app and to determine strategies used by agencies that successfully sustained client use of A-CHESS. Methods Qualitative inquiry assessed staff perceptions about organizational attributes and strategies associated with sustained use of the mobile app, A-CHESS. A total of 73 interviews of clinicians and administrators were conducted. The initial interviews (n=36) occurred at the implementation of A-CHESS. Follow-up interviews (n=37) occurred approximately 12 and 24 months later. A coding scheme was developed and Multiuser NVivo was used to manage and analyze the blinded interview data. Results Successful strategies used by treatment providers to sustain A-CHESS included (1) strong leadership support, (2) use of client feedback reports to follow up on non-engaged clients, (3) identify passionate staff and incorporate A-CHESS discussions in weekly meetings, (4) develop A-CHESS guidelines related to client use, (5) establish internal work groups to engage clients, and (6) establish a financial strategy to sustain A-CHESS use. The study also identified attributes of A-CHESS that enhanced as well as inhibited its sustainability. Conclusions Mobile apps can play an important role in health care delivery. However, providers will need to develop strategies for engaging both staff and patients in ongoing use of the apps. They will also need to rework business processes to accommodate the changes in communication frequency and style, learn to use app data for decision making, and identify financing mechanisms for supporting these changes. PMID:26286257

[Community interventions among tobacco control strategies: coping with their definition and evaluation].

PubMed

D'Elia, Paolo; Coppo, Alessandro; Di Stefano, Francesca; Charrier, Lorena; Piccinelli, Cristiano; Molinar, Roberta; Senore, Carlo; Giordano, Livia; Segnan, Nereo

2008-01-01

Community interventions represent a key component of the current anti-smoking strategies. We propose a conceptual framework for classifying these interventions, based on the concept of community utilised in different studies. We identified 5 different focuses: geographical areas (i.e. city, county, region); targets (sub-group of a population); settings (school, workplace); culture and individual attitudes; multilevel networks. These two latter views refer to functional rather than to structural aspects of a community and they represent the most promising approaches to design intervention strategies. Communities are represented as a group of organizations, systems and social networks investigating individual, environmental and cultural factors that can strongly influence behavioural changes. The great heterogeneity in what the authors mean as community interventions has in our opinion affected the evaluation of their impact. To facilitate their evaluation and to contribute to the detection of determinants, as well as of barriers, it is necessary to compare community interventions sharing similar theoretical approaches and focuses. Also, studies aimed at assessing the steps of the implementation process of community programmes may allow to identify those components related to specific levels of intervention, thus enabling the generalisation of results. To reach this goal it may be helpful to combine study designs allowing for both quantitative and qualitative assessments, such as action research and participatory evaluation research.

Accurate Sample Assignment in a Multiplexed, Ultrasensitive, High-Throughput Sequencing Assay for Minimal Residual Disease.

PubMed

Bartram, Jack; Mountjoy, Edward; Brooks, Tony; Hancock, Jeremy; Williamson, Helen; Wright, Gary; Moppett, John; Goulden, Nick; Hubank, Mike

2016-07-01

High-throughput sequencing (HTS) (next-generation sequencing) of the rearranged Ig and T-cell receptor genes promises to be less expensive and more sensitive than current methods of monitoring minimal residual disease (MRD) in patients with acute lymphoblastic leukemia. However, the adoption of new approaches by clinical laboratories requires careful evaluation of all potential sources of error and the development of strategies to ensure the highest accuracy. Timely and efficient clinical use of HTS platforms will depend on combining multiple samples (multiplexing) in each sequencing run. Here we examine the Ig heavy-chain gene HTS on the Illumina MiSeq platform for MRD. We identify errors associated with multiplexing that could potentially impact the accuracy of MRD analysis. We optimize a strategy that combines high-purity, sequence-optimized oligonucleotides, dual indexing, and an error-aware demultiplexing approach to minimize errors and maximize sensitivity. We present a probability-based, demultiplexing pipeline Error-Aware Demultiplexer that is suitable for all MiSeq strategies and accurately assigns samples to the correct identifier without excessive loss of data. Finally, using controls quantified by digital PCR, we show that HTS-MRD can accurately detect as few as 1 in 10(6) copies of specific leukemic MRD. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Economic Outcomes with Anatomic versus Functional Diagnostic Testing for Coronary Artery Disease

PubMed Central

Mark, Daniel B.; Federspiel, Jerome J.; Cowper, Patricia A.; Anstrom, Kevin J.; Hoffmann, Udo; Patel, Manesh R.; Davidson-Ray, Linda; Daniels, Melanie R.; Cooper, Lawton S.; Knight, J. David; Lee, Kerry L.; Douglas, Pamela S.

2016-01-01

Background The PROMISE trial found that initial use of ≥64-slice multidetector computed tomographic angiography (CTA) versus functional diagnostic testing strategies did not improve clinical outcomes in stable symptomatic patients with suspected coronary artery disease (CAD) requiring noninvasive testing. Objective Economic analysis of PROMISE, a major secondary aim. Design Prospective economic study from the US perspective. Comparisons were made by intention-to-treat. Confidence intervals were calculated using bootstrap methods. Setting 190 U.S. centers Patients 9649 U.S. patients enrolled in PROMISE. Enrollment began July 2010 and completed September 2013. Median follow-up was 25 months. Measurements Technical costs of the initial (outpatient) testing strategy were estimated from Premier Research Database data. Hospital-based costs were estimated using hospital bills and Medicare cost-to-charge ratios. Physician fees were taken from the Medicare Fee Schedule. Costs were expressed in 2014 US dollars discounted at 3% and estimated out to 3 years using inverse probability weighting methods. Results The mean initial testing costs were: $174 for exercise ECG; $404 for CTA; $501 to $514 for (exercise, pharmacologic) stress echo; $946 to $1132 for (exercise, pharmacologic) stress nuclear. Mean costs at 90 days for the CTA strategy were $2494 versus $2240 for the functional strategy (mean difference $254, 95% CI −$634 to $906). The difference was associated with more revascularizations and catheterizations (4.25 per 100 patients) with CTA use. After 90 days, the mean cost difference between the arms out to 3 years remained small ($373). Limitations Cost weights for test strategies obtained from sources outside PROMISE. Conclusions CTA and functional diagnostic testing strategies in patients with suspected CAD have similar costs through three years of follow-up. PMID:27214597

Identification of a small molecule that overcomes HdmX-mediated suppression of p53

PubMed Central

Chakrabarti, Amit; Karan, Sukanya; Liu, Zhigang; Xia, Zhiqiang; Gundluru, Mahesh; Moreton, Stephen; Saunthararajah, Yogen; Jackson, Mark W; Agarwal, Mukesh K; Wald, David N

2016-01-01

Inactivation of the p53 tumor suppressor by mutation or overexpression of negative regulators occurs frequently in cancer. Since p53 plays a key role in regulating proliferation or apoptosis in response to DNA damaging chemotherapies, strategies aimed at reactivating p53 are increasingly being sought. Strategies to reactivate wild-type p53 include the use of small molecules capable of releasing wild-type p53 from key, cellular negative regulators, such as Hdm2 and HdmX. Derivatives of the Hdm2 antagonist Nutlin-3 are in clinical trials. However, Nutlin-3 specifically disrupts Hdm2-p53, leaving tumors harboring high levels of HdmX resistant to Nutlin-3 treatment. Here we identify CTX1, a novel small molecule that overcomes HdmX-mediated p53 repression. CTX1 binds directly to HdmX to prevent p53-HdmX complex formation, resulting in the rapidly induction of p53 in a DNA damage-independent manner. Treatment of a panel of cancer cells with CTX1 induced apoptosis or suppressed proliferation and importantly, CTX1 demonstrates promising activity as a single agent in a mouse model of circulating primary human leukemia. CTX1 is a small molecule HdmX inhibitor that demonstrates promise as a cancer therapeutic candidate. PMID:26883273

Sulfur Mustard Research—Strategies for the Development of Improved Medical Therapy

PubMed Central

Kehe, Kai; Balszuweit, Frank; Emmler, Judith; Kreppel, Helmut; Jochum, Marianne; Thiermann, Horst

2008-01-01

Objective: Sulfur mustard (SM) is a bifunctional alkylating substance being used as chemical warfare agent (vesicant). It is still regarded as a significant threat in chemical warfare and terrorism. Exposure to SM produces cutaneous blisters, respiratory and gastrointestinal tract injury, eye lesions, and bone marrow depression. Victims of World War I as well as those of the Iran-Iraq war have suffered from devastating chronic health impairment. Even decades after exposure, severe long-term effects like chronic obstructive lung disease, lung fibrosis, recurrent corneal ulcer disease, chronic conjunctivitis, abnormal pigmentation of the skin, and different forms of cancer have been diagnosed. Methods: This review briefly summarizes the scientific literature and own results concerning detection, organ toxicity of SM, its proposed toxicodynamic actions, and strategies for the development of improved medical therapy. Results: Despite extensive research efforts during the last century, efficient antidotes against SM have not yet been generated because its mechanism of action is not fully understood. However, deeper insights into these mechanisms gained in the last decade and promising developments of new drugs now offer new chances to minimize SM-induced organ damage and late effects. Conclusion: Polymerase inhibitors, anti-inflammatory drugs, antioxidants, matrix metalloproteinase inhibitors, and probably regulators of DNA damage repair are identified as promising approaches to improve treatment. PMID:18615149

Lunasin-aspirin combination against NIH/3T3 cells transformation induced by chemical carcinogens.

PubMed

Hsieh, Chia-Chien; Hernández-Ledesma, Blanca; de Lumen, Ben O

2011-06-01

Carcinogenesis is a multistage process involving a number of molecular pathways sensitive to intervention. Chemoprevention is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. To achieve greater inhibitory effects on cancer cells, combination of two or more chemopreventive agents is commonly considered as a better preventive and/or therapeutic strategy. Lunasin is a promising cancer preventive peptide identified in soybean and other seeds. Its efficacy has been demonstrated by both in vitro and in vivo models. This peptide has been found to inhibit human breast cancer MDA-MB-231 cells proliferation, suppressing cell cycle progress and inducing cell apoptosis. Moreover, lunasin potentiates the effects on these cells of different synthetic and natural compounds, such as aspirin and anacardic acid. This study explored the role of lunasin, alone and in combination with aspirin and anacardic acid on cell proliferation and foci formation of transformed NIH/3T3 cells induced by chemical carcinogens 7,12-dimethylbenz[a]anthracene or 3-methylcholanthrene. The results revealed that lunasin, acting as a single agent, inhibits cell proliferation and foci formation. When combined with aspirin, these effects were significantly increased, indicating that this combination might be a promising strategy to prevent/treat cancer induced by chemical carcinogens.

Neuromuscular Regeneration: Perspective on the Application of Mesenchymal Stem Cells and Their Secretion Products

PubMed Central

Caseiro, Ana Rita; Pereira, Tiago; Ivanova, Galya; Luís, Ana Lúcia; Maurício, Ana Colette

2016-01-01

Mesenchymal stem cells are posing as a promising character in the most recent therapeutic strategies and, since their discovery, extensive knowledge on their features and functions has been gained. In recent years, innovative sources have been disclosed in alternative to the bone marrow, conveying their associated ethical concerns and ease of harvest, such as the umbilical cord tissue and the dental pulp. These are also amenable of cryopreservation and thawing for desired purposes, in benefit of the donor itself or other patients in pressing need. These sources present promising possibilities in becoming useful cell sources for therapeutic applications in the forthcoming years. Effective and potential applications of these cellular-based strategies for the regeneration of peripheral nerve are overviewed, documenting recent advances and identified issues for this research area in the near future. Finally, besides the differentiation capacities attributed to mesenchymal stem cells, advances in the recognition of their effective mode of action in the regenerative theatre have led to a new area of interest: the mesenchymal stem cells' secretome. The paracrine modulatory pathway appears to be a major mechanism by which these are beneficial to nerve regeneration and comprehension on the specific growth factors, cytokine, and extracellular molecules secretion profiles is therefore of great interest. PMID:26880998

Identifying promising accessions of cherry tomato: a sensory strategy using consumers and chefs.

PubMed

Rocha, Mariella C; Deliza, Rosires; Ares, Gastón; Freitas, Daniela De G C; Silva, Aline L S; Carmo, Margarida G F; Abboud, Antonio C S

2013-06-01

An increased production of cherry and gourmet tomato cultivars that are harvested at advanced colour stages and sold at a higher price has been observed in the last 10 years. In this context, producers need information on the sensory characteristics of new cultivars and their perception by potential consumers. The aim of the present work was to obtain a sensory characterisation of nine cherry tomato cultivars produced under Brazilian organic cultivation conditions from a chef and consumer perspective. Nine organic cherry tomato genotypes were evaluated by ten chefs using an open-ended question and by 110 consumers using a check-all-that-apply question. Both methodologies provided similar information on the sensory characteristics of the cherry tomato accessions. The superimposed representation of the samples in a multiple factor analysis was similar for consumers' and chefs' descriptions (RV coefficient 0.728), although they used different methodologies. According to both panels, cherry tomatoes were sorted into five groups of samples with similar sensory characteristics. Results from the present work may provide information to help organic producers in the selection of the most promising cultivars for cultivation, taking into account consumers' and chefs' perceptions, as well as in the design of communication and marketing strategies. © 2012 Society of Chemical Industry.

Discovery of benzofuran-3(2H)-one derivatives as novel DRAK2 inhibitors that protect islet β-cells from apoptosis.

PubMed

Wang, Sheng; Xu, Lei; Lu, Yu-Ting; Liu, Yu-Fei; Han, Bing; Liu, Ting; Tang, Jie; Li, Jia; Wu, Jiangping; Li, Jing-Ya; Yu, Li-Fang; Yang, Fan

2017-04-21

Death-associated protein kinase-related apoptosis-inducing kinase-2 (DRAK2) is a serine/threonine kinase that plays a key role in a wide variety of cell death signaling pathways. Inhibition of DRAK2 was found to efficiently protect islet β-cells from apoptosis and hence DRAK2 inhibitors represent a promising therapeutic strategy for the treatment of diabetes. Only very few chemical entities targeting DRAK2 are currently known. We carried out a high throughput screening and identified compound 4 as a moderate DRAK2 inhibitor with an IC 50 value of 3.15 μM. Subsequent SAR studies of hit compound 4 led to the development of novel benzofuran-3(2H)-one series of DRAK2 inhibitors with improved potency and favorable selectivity profiles against 26 selected kinases. Importantly, most potent compounds 40 (IC 50  = 0.33 μM) and 41 (IC 50  = 0.25 μM) were found to protect islet β-cells from apoptosis in dose-dependent manners. These data support the notion that small molecule inhibitors of DRAK2 represents a promising strategy for the treatment of diabetes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

(Meta)communication strategies in inclusive classes for deaf students.

PubMed

Kelman, Celeste Azulay; Branco, Angela Uchôa

2009-01-01

How can an inclusive classroom for deaf students be successful? The use of metacommunication strategies by teachers and hearing peers seems promising. Schools that promote this approach tend to improve deaf students' psychosocial development and academic achievement. However, this is not a general rule. The present study identifies the elements of success, with the investigators basing their analysis on extensive observation of 4 bilingual classes conducted by regular education and specialized teachers. The study was conducted in 3 public elementary schools in Brasilia, Brazil. Data were collected through direct observation (156 hours) and video recording (34 hours). Results were qualitatively analyzed from a microgenetic perspective. The investigators devised 14 categories of social interaction, e.g., visual contact and responsivity, multimodal communication, co-construction of meanings, flexible use of space, and sign language instruction for hearing students.

A comparison of financial performance, organizational characteristics and management strategy among rural and urban nursing facilities.

PubMed

Smith, H L; Piland, N F; Fisher, N

1992-01-01

Despite efforts to deinstitutionalize long-term care, it is estimated that 43 percent of the elderly will use a nursing facility at some point. Whether sufficient nursing facility services will be available to rural elderly is debatable due to cutbacks in governmental expenditures and recent financial losses among nursing facilities. This paper explores the challenges confronting rural nursing facilities in maintaining their viability and strategies that might be considered to improve their longevity. A comparative analysis of 18 urban and 34 rural nursing facilities in New Mexico is used in identifying promising strategic adaptations available to rural facilities. Among other considerations, rural facilities should strive to enhance revenue streams, implement strict cost control measures, emphasize broader promotional tactics, and diversify services commensurate with the constraints of the communities and populations served.

Damage to the microbial cell membrane during pyrolytic sugar utilization and strategies for increasing resistance.

PubMed

Jin, Tao; Rover, Marjorie R; Petersen, Elspeth M; Chi, Zhanyou; Smith, Ryan G; Brown, Robert C; Wen, Zhiyou; Jarboe, Laura R

2017-09-01

Lignocellulosic biomass is an appealing feedstock for the production of biorenewable fuels and chemicals, and thermochemical processing is a promising method for depolymerizing it into sugars. However, trace compounds in this pyrolytic sugar syrup are inhibitory to microbial biocatalysts. This study demonstrates that hydrophobic inhibitors damage the cell membrane of ethanologenic Escherichia coli KO11+lgk. Adaptive evolution was employed to identify design strategies for improving pyrolytic sugar tolerance and utilization. Characterization of the resulting evolved strain indicates that increased resistance to the membrane-damaging effects of the pyrolytic sugars can be attributed to a glutamine to leucine mutation at position 29 of carbon storage regulator CsrA. This single amino acid change is sufficient for decreasing EPS protein production and increasing membrane integrity when exposed to pyrolytic sugars.

Chromoendoscopy and Advanced Imaging Technologies for Surveillance of Patients with IBD

PubMed Central

Barkin, Jodie A.; Abreu, Maria T.

2012-01-01

Inflammatory bowel disease patients with long-standing colitis have an increased risk of colorectal cancer. The high rate of interval colitis-associated cancers among patients who adhere to a nontargeted, random biopsy surveillance strategy underlies the need for improved methods of early dysplasia detection. Compelling evidence supports the efficacy of chromoendoscopy for increasing the detection rate of dysplasia; however, this technology is currently underutilized in the clinical setting. Other contrast-based technologies—including confocal laser endomicroscopy (Pentax), endocytoscopy, multiband imaging, i-scan (Pentax), and molecular-targeted techniques—show promise in the detection of dysplasia in patients with inflammatory bowel disease. The strategies currently available for identifying patients with dysplasia or colitis-associated cancers remain inadequate and need to demonstrate both cost and time efficiency before they can be adopted in community-based practices. PMID:24693269

Near-optimal strategies for sub-decimeter satellite tracking with GPS

NASA Technical Reports Server (NTRS)

Yunck, Thomas P.; Wu, Sien-Chong; Wu, Jiun-Tsong

1986-01-01

Decimeter tracking of low Earth orbiters using differential Global Positioning System (GPS) techniques is discussed. A precisely known global network of GPS ground receivers and a receiver aboard the user satellite are needed, and all techniques simultaneously estimate the user and GPS satellite orbits. Strategies include a purely geometric, a fully dynamic, and a hybrid strategy. The last combines dynamic GPS solutions with a geometric user solution. Two powerful extensions of the hybrid strategy show the most promise. The first uses an optimized synthesis of dynamics and geometry in the user solution, while the second uses a gravity adjustment method to exploit data from repeat ground tracks. These techniques promise to deliver subdecimeter accuracy down to the lowest satellite altitudes.

Novel Approaches to Pulmonary Arterial Hypertension Drug Discovery

PubMed Central

Sung, Yon K.; Yuan, Ke; de Jesus Perez, Vinicio A.

2016-01-01

Introduction Pulmonary arterial hypertension (PAH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. The goal of drug development for PAH is to develop effective therapies that halt, or ideally, reverse the obliterative vasculopathy that results in vessel loss and obstruction of blood flow to the lungs. Areas Covered This review summarizes the current approach to candidate discovery in PAH and discusses the currently available drug discovery methods that should be implemented to prioritize targets and obtain a comprehensive pharmacological profile of promising compounds with well-defined mechanisms. Expert opinion To improve the successful identification of leading drug candidates, it is necessary that traditional pre-clinical studies are combined with drug screening strategies that maximize the characterization of biological activity and identify relevant off-target effects that could hinder the clinical efficacy of the compound when tested in human subjects. A successful drug discovery strategy in PAH will require collaboration of clinician scientists with medicinal chemists and pharmacologists who can identify compounds with an adequate safety profile and biological activity against relevant disease mechanisms. PMID:26901465

Single and Multiple Microphone Noise Reduction Strategies in Cochlear Implants

PubMed Central

Azimi, Behnam; Hu, Yi; Friedland, David R.

2012-01-01

To restore hearing sensation, cochlear implants deliver electrical pulses to the auditory nerve by relying on sophisticated signal processing algorithms that convert acoustic inputs to electrical stimuli. Although individuals fitted with cochlear implants perform well in quiet, in the presence of background noise, the speech intelligibility of cochlear implant listeners is more susceptible to background noise than that of normal hearing listeners. Traditionally, to increase performance in noise, single-microphone noise reduction strategies have been used. More recently, a number of approaches have suggested that speech intelligibility in noise can be improved further by making use of two or more microphones, instead. Processing strategies based on multiple microphones can better exploit the spatial diversity of speech and noise because such strategies rely mostly on spatial information about the relative position of competing sound sources. In this article, we identify and elucidate the most significant theoretical aspects that underpin single- and multi-microphone noise reduction strategies for cochlear implants. More analytically, we focus on strategies of both types that have been shown to be promising for use in current-generation implant devices. We present data from past and more recent studies, and furthermore we outline the direction that future research in the area of noise reduction for cochlear implants could follow. PMID:22923425

The Antioxidant Additive Approach for Alzheimer's Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators.

PubMed

Benchekroun, Mohamed; Romero, Alejandro; Egea, Javier; León, Rafael; Michalska, Patrycja; Buendía, Izaskun; Jimeno, María Luisa; Jun, Daniel; Janockova, Jana; Sepsova, Vendula; Soukup, Ondrej; Bautista-Aguilera, Oscar M; Refouvelet, Bernard; Ouari, Olivier; Marco-Contelles, José; Ismaili, Lhassane

2016-11-10

Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway.

Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

PubMed Central

Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

2013-01-01

Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

Strategies for Achieving Whole-Practice Engagement and Buy-in to the Patient-Centered Medical Home

PubMed Central

Bleser, William K.; Miller-Day, Michelle; Naughton, Dana; Bricker, Patricia L.; Cronholm, Peter F.; Gabbay, Robert A.

2014-01-01

PURPOSE The current model of primary care in the United States limits physicians’ ability to offer high-quality care. The patient-centered medical home (PCMH) shows promise in addressing provision of high-quality care, but achieving a PCMH practice model often requires comprehensive organizational change. Guided by Solberg’s conceptual framework for practice improvement, which argues for shared prioritization of improvement and change, we describe strategies for obtaining organizational buy-in to and whole-staff engagement of PCMH transformation and practice improvement. METHODS Semistructured interviews with 136 individuals and 7 focus groups involving 48 individuals were conducted in 20 small- to mid-sized medical practices in Pennsylvania during the first regional rollout of a statewide PCMH initiative. For this study, we analyzed interview transcripts, monthly narrative reports, and observer notes from site visits to identify discourse pertaining to organizational buy-in and strategies for securing buy-in from personnel. Using a consensual qualitative research approach, data were reduced, synthesized, and managed using qualitative data management and analysis software. RESULTS We identified 13 distinct strategies used to obtain practice buy-in, reflecting 3 overarching lessons that facilitate practice buy-in: (1) effective communication and internal PCMH campaigns, (2) effective resource utilization, and (3) creation of a team environment. CONCLUSION Our study provides a list of strategies useful for facilitating PCMH transformation in primary care. These strategies can be investigated empirically in future research, used to guide medical practices undergoing or considering PCMH transformation, and used to inform health care policy makers. Our study findings also extend Solberg’s conceptual framework for practice improvement to include buy-in as a necessary condition across all elements of the change process. PMID:24445102

PubMed search strings for the study of agricultural workers' diseases.

PubMed

Mattioli, Stefano; Gori, Davide; Di Gregori, Valentina; Ricotta, Lara; Baldasseroni, Alberto; Farioli, Andrea; Zanardi, Francesca; Galletti, Stefania; Colosio, Claudio; Curti, Stefania; Violante, Francesco S

2013-12-01

Several optimized search strategies have been developed in Medicine, and more recently in Occupational Medicine. The aim of this study was to identify efficient PubMed search strategies to retrieve articles regarding putative occupational determinants of agricultural workers' diseases. We selected the Medical Subjects Heading (MeSH) term agricultural workers' diseases and six MeSH terms describing farm work (agriculture, agrochemicals NOT pesticides, animal husbandry, pesticides, rural health, rural population) alongside 61 other promising terms. We estimated proportions of articles containing potentially pertinent information regarding occupational etiology to formulate two search strategies (one "more specific," one "more sensitive"). We applied these strategies to retrieve information on the possible occupational etiology among agricultural workers of kidney cancer, knee osteoarthritis, and multiple sclerosis. We evaluated the number of needed to read (NNR) abstracts to identify one potentially pertinent article in the context of these pathologies. The "more specific" search string was based on the combination of terms that yielded the highest proportion (40%) of potentially pertinent abstracts. The "more sensitive" string was based on use of broader search fields and additional coverage provided by other search terms under study. Using the "more specific" string, the NNR to find one potentially pertinent article were: 1.1 for kidney cancer; 1.4 for knee osteoarthritis; 1.2 for multiple sclerosis. Using the sensitive strategy, the NNR were 1.4, 3.6, and 6.3, respectively. The proposed strings could help health care professionals explore putative occupational etiology for agricultural workers' diseases (even if not generally thought to be work related). © 2013 Wiley Periodicals, Inc.

Trait-based characterisation of soil exploitation strategies of banana, weeds and cover plant species

PubMed Central

Tardy, Florence; Damour, Gaëlle; Dorel, Marc; Moreau, Delphine

2017-01-01

Cover plants can be introduced in cropping systems to provide agroecosystem services, including weed control via competition for resources. There is currently no consensus on how to identify the best cover plant species, while trait-based approaches are promising for screening plant species due to their agroecosystem service provision potential. This study was carried out to characterize soil exploitation strategies of cover plant species in banana agroecosystems using a trait-based approach, and in turn identify cover plant species with a high weed control potential via competition for soil resources in banana cropping systems. A field experiment was conducted on 17 cover plant species, two weed species and two banana cultivars grown individually. Four functional traits were measured. Two of them (i.e., the size of the zone explored by roots and the root impact density) were used to characterize root system soil exploration patterns. Two other traits (i.e., specific root length and root diameter) were used to characterize resource acquisition within the soil zone explored by the roots. All studied traits exhibited marked variations among species. The findings suggested a trade-off between the abilities of species to develop a limited number of large diameter roots exploring a large soil zone versus many thin roots exploring a smaller soil zone. Three soil-resource exploitation strategies were identified among species: (i) with large diameter roots that explore a large soil zone; (ii) with small diameter roots and a high specific length that explore a smaller soil zone; and (iii) with a high total root-impact density and an intermediate specific root length that explore the uppermost soil layers. Interestingly, in our panel of species, no correlations with regard to belowground and aboveground strategies were noted: species with an acquisitive belowground strategy could display an acquisitive or a conservative aboveground strategy. The findings of this study illustrated that a trait-based approach could be used to identify plant species with potential for competing with weeds, while minimising competition with banana. Six of the 17 studied cover crop species were identified as having this potential. The next step will be to assess them for their weed control performances in banana cropping systems with low reliance on herbicides. PMID:28257454

Trait-based characterisation of soil exploitation strategies of banana, weeds and cover plant species.

PubMed

Tardy, Florence; Damour, Gaëlle; Dorel, Marc; Moreau, Delphine

2017-01-01

Cover plants can be introduced in cropping systems to provide agroecosystem services, including weed control via competition for resources. There is currently no consensus on how to identify the best cover plant species, while trait-based approaches are promising for screening plant species due to their agroecosystem service provision potential. This study was carried out to characterize soil exploitation strategies of cover plant species in banana agroecosystems using a trait-based approach, and in turn identify cover plant species with a high weed control potential via competition for soil resources in banana cropping systems. A field experiment was conducted on 17 cover plant species, two weed species and two banana cultivars grown individually. Four functional traits were measured. Two of them (i.e., the size of the zone explored by roots and the root impact density) were used to characterize root system soil exploration patterns. Two other traits (i.e., specific root length and root diameter) were used to characterize resource acquisition within the soil zone explored by the roots. All studied traits exhibited marked variations among species. The findings suggested a trade-off between the abilities of species to develop a limited number of large diameter roots exploring a large soil zone versus many thin roots exploring a smaller soil zone. Three soil-resource exploitation strategies were identified among species: (i) with large diameter roots that explore a large soil zone; (ii) with small diameter roots and a high specific length that explore a smaller soil zone; and (iii) with a high total root-impact density and an intermediate specific root length that explore the uppermost soil layers. Interestingly, in our panel of species, no correlations with regard to belowground and aboveground strategies were noted: species with an acquisitive belowground strategy could display an acquisitive or a conservative aboveground strategy. The findings of this study illustrated that a trait-based approach could be used to identify plant species with potential for competing with weeds, while minimising competition with banana. Six of the 17 studied cover crop species were identified as having this potential. The next step will be to assess them for their weed control performances in banana cropping systems with low reliance on herbicides.

Bringing Promise to Washington, DC. The DC Promise Neighborhood Initiative. Program on Neighborhoods and Youth Development

ERIC Educational Resources Information Center

Comey, Jennifer; Scott, Molly M.; Popkin, Susan J.; Falkenburger, Elsa

2012-01-01

The U.S. Department of Education's Promise Neighborhood Initiative (DCPNI) is one of the Obama administration's major antipoverty initiatives and a core strategy of the White House's Neighborhood Revitalization Initiative. It is intended to improve educational outcomes by creating a continuum of school readiness, academic services, and family and…

Strategies for Hard Times in Higher Education.

ERIC Educational Resources Information Center

Desfosses, Louis R.

1996-01-01

Planning and management strategies used in the private sector have practical applications for higher education in a period of systemic and organizational stress. Promising strategies include organizational delayering; employee empowerment; boundless thinking, problem-solving teams; accelerated processes; quality management and improvement; and…

Design Strategies for Aptamer-Based Biosensors

PubMed Central

Han, Kun; Liang, Zhiqiang; Zhou, Nandi

2010-01-01

Aptamers have been widely used as recognition elements for biosensor construction, especially in the detection of proteins or small molecule targets, and regarded as promising alternatives for antibodies in bioassay areas. In this review, we present an overview of reported design strategies for the fabrication of biosensors and classify them into four basic modes: target-induced structure switching mode, sandwich or sandwich-like mode, target-induced dissociation/displacement mode and competitive replacement mode. In view of the unprecedented advantages brought about by aptamers and smart design strategies, aptamer-based biosensors are expected to be one of the most promising devices in bioassay related applications. PMID:22399891

Cost-effectiveness of Alternative Colonoscopy Surveillance Strategies to Mitigate Metachronous Colorectal Cancer Incidence

PubMed Central

ERENAY, FATIH SAFA; ALAGOZ, OGUZHAN; BANERJEE, RITESH; SAID, ADNAN; CIMA, ROBERT

2016-01-01

BACKGROUND Metachronous Colorectal Cancer (MCRC) incidence amongst colorectal cancer (CRC) survivors varies significantly and the optimal colonoscopy surveillance practice to mitigate MCRC incidence is unknown. METHODS We conducted a cost-effectiveness analysis by comparing performances of the US Multi-Society Task Force guideline and all clinically-reasonable colonoscopy surveillance strategies among 50–79-year-old post-treatment CRC patients using a computer-simulation model. RESULTS The US guideline [(1,3,5)] recommends the first colonoscopy 1-year after treatment while the second and third colonoscopies are repeated with 3- and 5-year intervals. We identified some promising alternative cost-effective strategies. Compared to the US guideline under various scenarios for 20-year period, 1) reducing the surveillance interval of the guideline after the first colonoscopy by 1-year [(1,2,5)] saves/prevents up to 78 discounted-life-years and 23 MCRCs per 1000-patients (incremental cost-effectiveness ratio (ICER)≤$23,270/life-year); 2) reducing the intervals after the first and second negative colonoscopy by 1-year [(1,2,4)] saves/prevents up to 109 discounted-life-years and 36 MCRCs (ICER≤$52,155/life-year); 3) (1,2,3) saves/prevents up to 141 discounted-life-years and 50 MCRCs (ICER≤$68,822/life-year). These strategies require up to 1100 additional colonoscopies per 1000-patients. Although, the US guideline may not be cost-effective compared to less-intensive oncology guideline (3,3,5) (ICER can be as high as $140,000/LY), the promising strategies are cost-effective compared to such less-intensive guidelines unless cumulative MCRC incidence is very low. CONCLUSIONS The US guideline might be improved by slightly increasing the surveillance intensity at the expense of moderately increased cost. More research is warranted to explore the benefits/harms of such practices. PMID:27248907

Community Health Workers in the United States: Challenges in Identifying, Surveying, and Supporting the Workforce.

PubMed

Sabo, Samantha; Allen, Caitlin G; Sutkowi, Katherine; Wennerstrom, Ashley

2017-12-01

Community health workers (CHWs) are members of a growing profession in the United States. Studying this dynamic labor force is challenging, in part because its members have more than 100 different job titles. The demand for timely, accurate information about CHWs is increasing as the profession gains recognition for its ability to improve health outcomes and reduce costs. Although numerous surveys of CHWs have been conducted, the field lacks well-delineated methods for gaining access to this hard-to-identify workforce. We outline methods for surveying CHWs and promising approaches to engage the workforce and other stakeholders in conducting local, state, and national studies. We also highlight successful strategies to overcome challenges in CHW surveys and future directions for surveying the field.

Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening.

PubMed

Boedeker, Enole; Friedel, Godehard; Walles, Thorsten

2012-05-01

Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as 'electronic noses', may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients.

Inhibition of CatA: an emerging strategy for the treatment of heart failure.

PubMed

Ruf, Sven; Buning, Christian; Schreuder, Herman; Linz, Wolfgang; Hübschle, Thomas; Linz, Dominik; Ruetten, Hartmut; Wirth, Klaus; Sadowski, Thorsten

2013-03-01

The lysosomal serine carboxypeptidase CatA has a very important and well-known structural function as well as a, so far, less explored catalytic function. A complete loss of the CatA protein results in the lysosomal storage disease galactosialidosis caused by intralysosomal degradation of β-galactosidase and neuraminidase 1. However, mice with a catalytically inactive CatA enzyme show no signs of this disease. This observation establishes a clear distinction between structural and catalytic functions of the CatA enzyme. Recently, several classes of orally bioavailable synthetic inhibitors of CatA have been identified. Pharmacological studies in rodents indicate a remarkable influence of CatA inhibition on cardiovascular disease progression and identify CatA as a promising novel target for the treatment of heart failure.

Virtual Reality as a Promising Strategy in the Assessment and Treatment of Bulimia Nervosa and Binge Eating Disorder: A Systematic Review.

PubMed

de Carvalho, Marcele Regine; Dias, Thiago Rodrigues de Santana; Duchesne, Monica; Nardi, Antonio Egidio; Appolinario, Jose Carlos

2017-07-09

Several lines of evidence suggest that Virtual Reality (VR) has a potential utility in eating disorders. The objective of this study is to review the literature on the use of VR in bulimia nervosa (BN) and binge eating disorder (BED). Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement for reporting systematic reviews, we performed a PubMed, Web of Knowledge and SCOPUS search to identify studies employing VR in the assessment and treatment of BN and BED. The following search terms were used: "virtual reality", "eating disorders", "binge eating", and "bulimia nervosa". From the 420 articles identified, 19 were selected, nine investigated VR in assessment and 10 were treatment studies (one case-report, two non-controlled and six randomized controlled trials). The studies using VR in BN and BED are at an early stage. However, considering the available evidence, the use of VR in the assessment of those conditions showed some promise in identifying: (1) how those patients experienced their body image; and (2) environments or specific kinds of foods that may trigger binge-purging cycle. Some studies using VR-based environments associated to cognitive behavioral techniques showed their potential utility in improving motivation for change, self-esteem, body image disturbances and in reducing binge eating and purging behavior.

Establishing glucose- and ABA-regulated transcription networks in Arabidopsis by microarray analysis and promoter classification using a Relevance Vector Machine.

PubMed

Li, Yunhai; Lee, Kee Khoon; Walsh, Sean; Smith, Caroline; Hadingham, Sophie; Sorefan, Karim; Cawley, Gavin; Bevan, Michael W

2006-03-01

Establishing transcriptional regulatory networks by analysis of gene expression data and promoter sequences shows great promise. We developed a novel promoter classification method using a Relevance Vector Machine (RVM) and Bayesian statistical principles to identify discriminatory features in the promoter sequences of genes that can correctly classify transcriptional responses. The method was applied to microarray data obtained from Arabidopsis seedlings treated with glucose or abscisic acid (ABA). Of those genes showing >2.5-fold changes in expression level, approximately 70% were correctly predicted as being up- or down-regulated (under 10-fold cross-validation), based on the presence or absence of a small set of discriminative promoter motifs. Many of these motifs have known regulatory functions in sugar- and ABA-mediated gene expression. One promoter motif that was not known to be involved in glucose-responsive gene expression was identified as the strongest classifier of glucose-up-regulated gene expression. We show it confers glucose-responsive gene expression in conjunction with another promoter motif, thus validating the classification method. We were able to establish a detailed model of glucose and ABA transcriptional regulatory networks and their interactions, which will help us to understand the mechanisms linking metabolism with growth in Arabidopsis. This study shows that machine learning strategies coupled to Bayesian statistical methods hold significant promise for identifying functionally significant promoter sequences.

Virtual Reality as a Promising Strategy in the Assessment and Treatment of Bulimia Nervosa and Binge Eating Disorder: A Systematic Review

PubMed Central

Dias, Thiago Rodrigues de Santana; Duchesne, Monica; Appolinario, Jose Carlos

2017-01-01

Several lines of evidence suggest that Virtual Reality (VR) has a potential utility in eating disorders. The objective of this study is to review the literature on the use of VR in bulimia nervosa (BN) and binge eating disorder (BED). Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement for reporting systematic reviews, we performed a PubMed, Web of Knowledge and SCOPUS search to identify studies employing VR in the assessment and treatment of BN and BED. The following search terms were used: “virtual reality”, “eating disorders”, “binge eating”, and “bulimia nervosa”. From the 420 articles identified, 19 were selected, nine investigated VR in assessment and 10 were treatment studies (one case-report, two non-controlled and six randomized controlled trials). The studies using VR in BN and BED are at an early stage. However, considering the available evidence, the use of VR in the assessment of those conditions showed some promise in identifying: (1) how those patients experienced their body image; and (2) environments or specific kinds of foods that may trigger binge–purging cycle. Some studies using VR-based environments associated to cognitive behavioral techniques showed their potential utility in improving motivation for change, self-esteem, body image disturbances and in reducing binge eating and purging behavior. PMID:28698483

Developing a conservation strategy to maximize persistence of an endangered freshwater mussel species while considering management effectiveness and cost

USGS Publications Warehouse

Smith, David R.; McRae, Sarah E.; Augspurger, Tom; Ratcliffe, Judith A.; Nichols, Robert B.; Eads, Chris B.; Savidge, Tim; Bogan, Arthur E.

2015-01-01

We used a structured decision-making process to develop conservation strategies to increase persistence of Dwarf Wedgemussel (Alasmidonta heterodon) in North Carolina, USA, while accounting for uncertainty in management effectiveness and considering costs. Alternative conservation strategies were portfolios of management actions that differed by location of management actions on the landscape. Objectives of the conservation strategy were to maximize species persistence, maintain genetic diversity, maximize public support, and minimize management costs. We compared 4 conservation strategies: 1) the ‘status quo’ strategy represented current management, 2) the ‘protect the best’ strategy focused on protecting the best populations in the Tar River basin, 3) the ‘expand the distribution’ strategy focused on management of extant populations and establishment of new populations in the Neuse River basin, and 4) the ‘hybrid’ strategy combined elements of each strategy to balance conservation in the Tar and Neuse River basins. A population model informed requirements for population management, and experts projected performance of alternative strategies over a 20-y period. The optimal strategy depended on the relative value placed on competing objectives, which can vary among stakeholders. The protect the best and hybrid strategies were optimal across a wide range of relative values with 2 exceptions: 1) if minimizing management cost was of overriding concern, then status quo was optimal, or 2) if maximizing population persistence in the Neuse River basin was emphasized, then expand the distribution strategy was optimal. The optimal strategy was robust to uncertainty in management effectiveness. Overall, the structured decision process can help identify the most promising strategies for endangered species conservation that maximize conservation benefit given the constraint of limited funding.

Mental health system governance in Nigeria: challenges, opportunities and strategies for improvement.

PubMed

Abdulmalik, J; Kola, L; Gureje, O

2016-01-01

A health systems approach to understanding efforts for improving health care services is gaining traction globally. A component of this approach focuses on health system governance (HSG), which can make or mar the successful implementation of health care interventions. Very few studies have explored HSG in low- and middle-income countries, including Nigeria. Studies focusing on mental health system governance, are even more of a rarity. This study evaluates the mental HSG of Nigeria with a view to understanding the challenges, opportunities and strategies for strengthening it. This study was conducted as part of the project, Emerging Mental Health Systems in Low and Middle Income Countries (Emerald). A multi-method study design was utilized to evaluate the mental HSG status of Nigeria. A situational analysis of the health policy and legal environment in the country was performed. Subsequently, 30 key informant interviews were conducted at national, state and district levels to explore the country's mental HSG. The existing policy, legislative and institutional framework for HSG in Nigeria reveals a complete exclusion of mental health in key health sector documents. The revised mental health policy is however promising. Using the Siddiqi framework categories, we identified pragmatic strategies for mental health system strengthening that include a consideration of existing challenges and opportunities within the system. The identified strategies provide a template for the subsequent activities of the Emerald Programme (and other interventions), towards strengthening the mental health system of Nigeria.

De novo characterization of the pine aphid Cinara pinitabulaeformis Zhang et Zhang transcriptome and analysis of genes relevant to pesticides

PubMed Central

Rebeca, Carballar-Lejarazú; Zhu, Xiaoli; Guo, Yajie; Lin, Qiannan; Hu, Xia; Wang, Rong; Liang, Guanghong; Guan, Xiong

2017-01-01

The pine aphid Cinara pinitabulaeformis Zhang et Zhang is the main pine pest in China, it causes pine needles to produce dense dew (honeydew) which can lead to sooty mold (black filamentous saprophytic ascomycetes). Although common chemical and physical strategies are used to prevent the disease caused by C. pinitabulaeformis Zhang et Zhang, new strategies based on biological and/or genetic approaches are promising to control and eradicate the disease. However, there is no information about genomics, proteomics or transcriptomics to allow the design of new control strategies for this pine aphid. We used next generation sequencing technology to sequence the transcriptome of C. pinitabulaeformis Zhang et Zhang and built a transcriptome database. We identified 80,259 unigenes assigned for Gene Ontology (GO) terms and information for a total of 11,609 classified unigenes was obtained in the Clusters of Orthologous Groups (COGs). A total of 10,806 annotated unigenes were analyzed to identify the represented biological pathways, among them 8,845 unigenes matched with 228 KEGG pathways. In addition, our data describe propagative viruses, nutrition-related genes, detoxification related molecules, olfactory related receptors, stressed-related protein, putative insecticide resistance genes and possible insecticide targets. Moreover, this study provides valuable information about putative insecticide resistance related genes and for the design of new genetic/biological based strategies to manage and control C. pinitabulaeformis Zhang et Zhang populations. PMID:28570707

Curbing the burden of lung cancer.

PubMed

Urman, Alexandra; Hosgood, H Dean

2016-06-01

Lung cancer contributes substantially to the global burden of disease and healthcare costs. New screening modalities using low-dose computerized tomography are promising tools for early detection leading to curative surgery. However, the screening and follow-up diagnostic procedures of these techniques may be costly. Focusing on prevention is an important factor to reduce the burden of screening, treatment, and lung cancer deaths. The International Agency for Research on Cancer has identified several lung carcinogens, which we believe can be considered actionable when developing prevention strategies. To curb the societal burden of lung cancer, healthcare resources need to be focused on early detection and screening and on mitigating exposure(s) of a person to known lung carcinogens, such as active tobacco smoking, household air pollution (HAP), and outdoor air pollution. Evidence has also suggested that these known lung carcinogens may be associated with genetic predispositions, supporting the hypothesis that lung cancers attributed to differing exposures may have developed from unique underlying genetic mechanisms attributed to the exposure of interest. For instance, smokingattributed lung cancer involves novel genetic markers of risk compared with HAP-attributed lung cancer. Therefore, genetic risk markers may be used in risk stratification to identify subpopulations that are at a higher risk for developing lung cancer attributed to a given exposure. Such targeted prevention strategies suggest that precision prevention strategies may be possible in the future; however, much work is needed to determine whether these strategies will be viable.

SEA and strategy formation theories: From three Ps to five Ps

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

Cherp, Aleh; Watt, Alan; Vinichenko, Vadim

2007-10-15

A transition to environmentally sustainable societies should involve a significant and comprehensive - strategic - change. Much of the promise of SEA is associated precisely with its perceived capacity to facilitate such a strategic transformation by influencing selected 'strategic decisions'. This paper examines the potential effectiveness and limitations of such an approach in light of contemporary organizational strategy theories. Most of these theories separate 'strategies' from 'decisions' and also transcend the notion of strategies as formal plans, policies and programs (PPPs). Instead, they consider strategies as 'five Ps', adding 'Position', 'Perspective', 'Pattern' and 'Ploy' to the 'Plan'. Lessons from organizationalmore » strategy formation give rise to the following challenges for SEA theory and practice: 1.How to assess and influence informal as well as formal aspects of strategic initiatives? 2.How to extend SEA 'beyond decisions' to address 'emergent strategies' where strategic action is not necessarily preceded by a decision? 3.How to ensure that knowledge provided as a result of SEA is strategically relevant and communicated to key players in strategy formation? 4.How to deal with an uncontrollable and unpredictable environment in which strategic initiatives unfold? 5.How to recognize those situations when SEA can have most strategic influence? This paper takes a step towards examining these challenges by exploring the intellectual history of SEA in light of the main strategy formation theories and by identifying directions in which the SEA discourse may be further enhanced to meet these five challenges.« less

Effective clinical education: strategies for teaching medical students and residents in the office.

PubMed

Cayley, William E

2011-08-01

Educating medical students and residents in the office presents the challenges of providing quality medical care, maintaining efficiency, and incorporating meaningful education for learners. Numerous teaching strategies to address these challenges have been described in the medical educational literature, but only a few teaching strategies have been evaluated for their impact on education and office practice. Literature on the impact of office-based teaching strategies on educational outcomes and on office efficiency was selected from a Pub Med search, from review of references in retrieved articles, and from the author's personal files. Two teaching strategies, "one-minute preceptor" (OMP) and "SNAPPS," have been shown to improve educational processes and outcomes. Two additional strategies, "Aunt Minnie" pattern recognition and "activated demonstration," show promise but have not been fully evaluated. None of these strategies has been shown to improve office efficiency. OMP and SNAPPS are strategies that can be used in office precepting to improve educational processes and outcomes, while pattern recognition and activated demonstration show promise but need further assessment. Additional areas of research also are suggested.

Application of a symbolic motion structure representation algorithm to identify upper extremity kinematic changes during a repetitive task.

PubMed

Whittaker, Rachel L; Park, Woojin; Dickerson, Clark R

2018-04-27

Efficient and holistic identification of fatigue-induced movement strategies can be limited by large between-subject variability in descriptors of joint angle data. One promising alternative to traditional, or computationally intensive methods is the symbolic motion structure representation algorithm (SMSR), which identifies the basic spatial-temporal structure of joint angle data using string descriptors of temporal joint angle trajectories. This study attempted to use the SMSR to identify changes in upper extremity time series joint angle data during a repetitive goal directed task causing muscle fatigue. Twenty-eight participants (15 M, 13 F) performed a seated repetitive task until fatigued. Upper extremity joint angles were extracted from motion capture for representative task cycles. SMSRs, averages and ranges of several joint angles were compared at the start and end of the repetitive task to identify kinematic changes with fatigue. At the group level, significant increases in the range of all joint angle data existed with large between-subject variability that posed a challenge to the interpretation of these fatigue-related changes. However, changes in the SMSRs across participants effectively summarized the adoption of adaptive movement strategies. This establishes SMSR as a viable, logical, and sensitive method of fatigue identification via kinematic changes, with novel application and pragmatism for visual assessment of fatigue development. Copyright © 2018 Elsevier Ltd. All rights reserved.

The use of SWOT analysis to explore and prioritize conservation and development strategies for local cattle breeds.

PubMed

Martín-Collado, D; Díaz, C; Mäki-Tanila, A; Colinet, F; Duclos, D; Hiemstra, S J; Gandini, G

2013-06-01

SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis is a tool widely used to help in decision making in complex systems. It suits to exploring the issues and measures related to the conservation and development of local breeds, as it allows the integration of many driving factors influencing breed dynamics. We developed a quantified SWOT method as a decision-making tool for identification and ranking of conservation and development strategies of local breeds, and applied it to a set of 13 cattle breeds of six European countries. The method has four steps: definition of the system, identification and grouping of the driving factors, quantification of the importance of driving factors and identification and prioritization of the strategies. The factors were determined following a multi-stakeholder approach and grouped with a three-level structure. Animal genetic resources expert groups ranked the factors, and a quantification process was implemented to identify and prioritize strategies. The proposed SWOT methodology allows analyzing the dynamics of local cattle breeds in a structured and systematic way. It is a flexible tool developed to assist different stakeholders in defining the strategies and actions. The quantification process allows the comparison of the driving factors and the prioritization of the strategies for the conservation and development of local cattle breeds. We identified 99 factors across the breeds. Although the situation is very heterogeneous, the future of these breeds may be promising. The most important strengths and weaknesses were related to production systems and farmers. The most important opportunities were found in marketing new products, whereas the most relevant threats were found in selling the current products. The across-breed strategies utility decreased as they gained specificity. Therefore, the strategies at European level should focus on general aspects and be flexible enough to be adapted to the country and breed specificities.

Pharmacotherapeutical strategies in the prevention of acute, vaso-occlusive pain in sickle cell disease: a systematic review

PubMed Central

Mager, David J.; Davis, Shyrin C. A. T.; Biemond, Bart J.

2017-01-01

Sickle-cell disease (SCD) is characterized by frequent and painful vaso-occlusive crises (VOCs). Various treatments have been evaluated over the years. However, a clear overview is lacking. The objective of this study was to systematically review all pharmacotherapeutical strategies in the prevention of VOCs beyond hydroxyurea. We performed a systematic literature search (MEDLINE, Embase, CENTRAL). Eligible studies were controlled clinical trials evaluating pharmacotherapeutical interventions targeting the reduction of VOCs in patients with SCD. Primary outcomes were the number or duration of SCD-related pain days, VOCs, or hospital admissions for VOCs. Secondary outcomes included time to first VOC or hospital admission for a VOC. A standardized data extraction sheet was used. The methodological quality of studies was assessed using Cochrane’s risk-of-bias tool. A total of 36 studies were included in this review, covering 26 different prophylactic interventions. The most promising interventions for reducing the frequency of either VOCs or hospitalizations were the oral antioxidants l-glutamine and ω-3 fatty acids and the IV antiadhesive agent crizanlizumab. Twenty-three studies did not show any beneficial effect of the intervention under investigation, and 6 studies were either too small or methodologically inadequate to draw conclusions. Because of the heterogeneity of interventions, no meta-analysis was performed. In conclusion, this review identified 3 promising pharmacotherapeutical strategies in the prevention of VOCs in SCD. Importantly, this study highlights the discrepancy between the significant burden of SCD worldwide and the low number of adequate trials performed. This review was registered at PROSPERO (CRD42015025250). PMID:29296801

Planning collision free paths for two cooperating robots using a divide-and-conquer C-space traversal heuristic

NASA Technical Reports Server (NTRS)

Weaver, Johnathan M.

1993-01-01

A method was developed to plan feasible and obstacle-avoiding paths for two spatial robots working cooperatively in a known static environment. Cooperating spatial robots as referred to herein are robots which work in 6D task space while simultaneously grasping and manipulating a common, rigid payload. The approach is configuration space (c-space) based and performs selective rather than exhaustive c-space mapping. No expensive precomputations are required. A novel, divide-and-conquer type of heuristic is used to guide the selective mapping process. The heuristic does not involve any robot, environment, or task specific assumptions. A technique was also developed which enables solution of the cooperating redundant robot path planning problem without requiring the use of inverse kinematics for a redundant robot. The path planning strategy involves first attempting to traverse along the configuration space vector from the start point towards the goal point. If an unsafe region is encountered, an intermediate via point is identified by conducting a systematic search in the hyperplane orthogonal to and bisecting the unsafe region of the vector. This process is repeatedly applied until a solution to the global path planning problem is obtained. The basic concept behind this strategy is that better local decisions at the beginning of the trouble region may be made if a possible way around the 'center' of the trouble region is known. Thus, rather than attempting paths which look promising locally (at the beginning of a trouble region) but which may not yield overall results, the heuristic attempts local strategies that appear promising for circumventing the unsafe region.

Exploring the potential for using results-based financing to address non-communicable diseases in low- and middle-income countries

PubMed Central

2013-01-01

Background The burden of disease due to non-communicable diseases (NCDs) is rising in low- and middle-income countries (LMICs) and funding for global health is increasingly limited. As a large contributor of development assistance for health, the US government has the potential to influence overall trends in NCDs. Results-based financing (RBF) has been proposed as a strategy to increase aid effectiveness and efficiency through incentives for positive performance and results in health programs, but its potential for addressing NCDs has not been explored. Methods Qualitative methods including literature review and key informant interviews were used to identify promising RBF mechanisms for addressing NCDs in resource-limited settings. Eight key informants identified by area of expertise participated in semi-structured interviews. Results The majority of RBF schemes to date have been applied to maternal and child health. Evidence from existing RBF programs suggests that RBF principles can be applied to health programs for NCDs. Several options were identified for US involvement with RBF for NCDs. Conclusion There is potential for the US to have a significant impact on NCDs in LMICs through a comprehensive RBF strategy for global health. RBF mechanisms should be tested for use in NCD programs through pilot programs incorporating robust impact evaluations. PMID:23368959

Exploring the potential for using results-based financing to address non-communicable diseases in low- and middle-income countries.

PubMed

Beane, Chelsey R; Hobbs, Suzanne Havala; Thirumurthy, Harsha

2013-02-01

The burden of disease due to non-communicable diseases (NCDs) is rising in low- and middle-income countries (LMICs) and funding for global health is increasingly limited. As a large contributor of development assistance for health, the US government has the potential to influence overall trends in NCDs. Results-based financing (RBF) has been proposed as a strategy to increase aid effectiveness and efficiency through incentives for positive performance and results in health programs, but its potential for addressing NCDs has not been explored. Qualitative methods including literature review and key informant interviews were used to identify promising RBF mechanisms for addressing NCDs in resource-limited settings. Eight key informants identified by area of expertise participated in semi-structured interviews. The majority of RBF schemes to date have been applied to maternal and child health. Evidence from existing RBF programs suggests that RBF principles can be applied to health programs for NCDs. Several options were identified for US involvement with RBF for NCDs. There is potential for the US to have a significant impact on NCDs in LMICs through a comprehensive RBF strategy for global health. RBF mechanisms should be tested for use in NCD programs through pilot programs incorporating robust impact evaluations.

Characterizing the syphilis epidemic among men who have sex with men in Lima, Peru to identify new treatment and control strategies.

PubMed

Deiss, Robert G; Leon, Segundo R; Konda, Kelika A; Brown, Brandon; Segura, Eddy R; Galea, Jerome T; Caceres, Carlos F; Klausner, Jeffrey D

2013-09-10

Syphilis is an important sexually transmitted infection (STI) with serious public health consequences. Among men who have sex with men (MSM) in Lima, the prevalence and incidence are extraordinarily high. Current syndromic approaches, however, fail to identify asymptomatic cases, and in settings where large proportions of individuals test positive again after treatment, it is frequently difficult to distinguish treatment failure from re-infection. Thus, new approaches are needed to improve treatment strategies and public health control efforts. Study participants will undergo baseline testing for syphilis infection along with a behavioral survey covering demographics, sexual behavior, drug and alcohol abuse and health-care seeking behavior. The cohort will be followed for 18 months at three-month intervals. Blood and earlobe scrapings will also be collected for T. pallidum DNA testing, to create molecular markers for subtyping. We will also perform cytokine testing on collected samples in order to create host immunologic profiles associated with recurrence, re-infection, treatment failure and success. Advances in social epidemiology, molecular typing and characterization of host immune responses will offer promise in developing new understandings of syphilis management. We will share our findings with the Peruvian Ministry of Health and other public health organizations, to identify new approaches of case detection and successful treatment.

Adolescent women as a key target population for community nutrition education programs in Indonesia.

PubMed

Savage, Amy; Februhartanty, Judhiastuty; Worsley, Anthony

2017-05-01

Adolescence is a critical life-stage that sets the foundation for health in adulthood. Adolescent women are a unique population and should be targeted as such for nutrition promotion activities. Using Indonesia as a case study, this qualitative study aimed to identify existing nutrition promotion programs aimed at adolescent girls, how best to target this population and effective recommendations to inform nutrition education program design for this important group. Semi-structured interviews and questionnaires were conducted with ten key informants working in public health in Indonesia. Interview transcripts were analysed and coded to identify key themes. No existing nutrition education programs targeting adolescent women in Indonesia were identified. Several strategies apply to nutrition programs for adolescent girls: 1) nutrition promotion messages that are relevant to the lifestyles and interests of adolescent women; 2) technology-based interventions show promise, however, they need to be appropriately targeted to sub-groups; 3) school remains an important setting; and 4) early marriage is an important issue affecting nutritional status and engagement of adolescent girls. The informants recommended that: 1) more research is needed about the underlying motivations for behaviour change among adolescent women and ways to effectively implement the identified engagement strategies; 2) adolescent girls should be included in program design to improve its suitability and uptake; and 3) government budget and policy support is crucial to success. Adolescent women are an important population group and more research is required to identify the optimal forms of engagement to improve nutrition programs for them.

Enhancing the Effectiveness of Smoking Treatment Research: Conceptual Bases and Progress

PubMed Central

Baker, Timothy B.; Collins, Linda M.; Mermelstein, Robin; Piper, Megan E.; Schlam, Tanya R.; Cook, Jessica W.; Bolt, Daniel M.; Smith, Stevens S.; Jorenby, Douglas E.; Fraser, David; Loh, Wei-Yin; Theobald, Wendy E.; Fiore, Michael C.

2015-01-01

Background and aims A chronic care strategy could potentially enhance the reach and effectiveness of smoking treatment by providing effective interventions for all smokers, including those who are initially unwilling to quit. This paper describes the conceptual bases of a National Cancer Institute-funded research program designed to develop an optimized, comprehensive, chronic care smoking treatment. Methods This research is grounded in three methodological approaches: 1) the Phase-Based Model, which guides the selection of intervention components to be experimentally evaluated for the different phases of smoking treatment (motivation, preparation, cessation, and maintenance); 2) the Multiphase Optimization Strategy (MOST), which guides the screening of intervention components via efficient experimental designs and, ultimately, the assembly of promising components into an optimized treatment package; and 3) pragmatic research methods, such as electronic health record recruitment, that facilitate the efficient translation of research findings into clinical practice. Using this foundation and working in primary care clinics, we conducted three factorial experiments (reported in three accompanying articles) to screen 15 motivation, preparation, cessation, and maintenance phase intervention components for possible inclusion in a chronic care smoking treatment program. Results This research identified intervention components with relatively strong evidence of effectiveness at particular phases of smoking treatment and it demonstrated the efficiency of the MOST approach in terms both of the number of intervention components tested and of the richness of the information yielded. Conclusions A new, synthesized research approach efficiently evaluates multiple intervention components to identify promising components for every phase of smoking treatment. Many intervention components interact with one another, supporting the use of factorial experiments in smoking treatment development. PMID:26581974

Metabolic analyses elucidate non-trivial gene targets for amplifying dihydroartemisinic acid production in yeast

PubMed Central

Misra, Ashish; Conway, Matthew F.; Johnnie, Joseph; Qureshi, Tabish M.; Lige, Bao; Derrick, Anne M.; Agbo, Eddy C.; Sriram, Ganesh

2013-01-01

Synthetic biology enables metabolic engineering of industrial microbes to synthesize value-added molecules. In this, a major challenge is the efficient redirection of carbon to the desired metabolic pathways. Pinpointing strategies toward this goal requires an in-depth investigation of the metabolic landscape of the organism, particularly primary metabolism, to identify precursor and cofactor availability for the target compound. The potent antimalarial therapeutic artemisinin and its precursors are promising candidate molecules for production in microbial hosts. Recent advances have demonstrated the production of artemisinin precursors in engineered yeast strains as an alternative to extraction from plants. We report the application of in silico and in vivo metabolic pathway analyses to identify metabolic engineering targets to improve the yield of the direct artemisinin precursor dihydroartemisinic acid (DHA) in yeast. First, in silico extreme pathway (ExPa) analysis identified NADPH-malic enzyme and the oxidative pentose phosphate pathway (PPP) as mechanisms to meet NADPH demand for DHA synthesis. Next, we compared key DHA-synthesizing ExPas to the metabolic flux distributions obtained from in vivo 13C metabolic flux analysis of a DHA-synthesizing strain. This comparison revealed that knocking out ethanol synthesis and overexpressing glucose-6-phosphate dehydrogenase in the oxidative PPP (gene YNL241C) or the NADPH-malic enzyme ME2 (YKL029C) are vital steps toward overproducing DHA. Finally, we employed in silico flux balance analysis and minimization of metabolic adjustment on a yeast genome-scale model to identify gene knockouts for improving DHA yields. The best strategy involved knockout of an oxaloacetate transporter (YKL120W) and an aspartate aminotransferase (YKL106W), and was predicted to improve DHA yields by 70-fold. Collectively, our work elucidates multiple non-trivial metabolic engineering strategies for improving DHA yield in yeast. PMID:23898325

Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury

PubMed Central

Embree, Mildred C.; Chen, Mo; Pylawka, Serhiy; Kong, Danielle; Iwaoka, George M.; Kalajzic, Ivo; Yao, Hai; Shi, Chancheng; Sun, Dongming; Sheu, Tzong-Jen; Koslovsky, David A.; Koch, Alia; Mao, Jeremy J.

2016-01-01

Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues. PMID:27721375

Health System Transformation through a Scalable, Actionable Innovation Strategy.

PubMed

Snowdon, Anne

2017-01-01

The authors who contributed to this issue of Healthcare Papers have provided rich insights into a promising innovation agenda to support transformational change aimed at achieving high-performing, person-centric health systems that are sustainable and deliver value. First and foremost, the commentaries make clear that a focused innovation agenda with defined goals, objectives and milestones is needed, if innovation is to be a viable and successful strategy to achieve health system transformation. To date, innovation has been a catch-all term for solving the many challenges health systems are experiencing. Yet, innovation on its own cannot fix all the ills of a health system; strategic goals and objectives are needed to define the way forward if innovation is to achieve value for Canadians. To this end, the authors identify goals and objectives that are worthy of serious consideration by all health system stakeholders.

In-silico guided discovery of novel CCR9 antagonists

NASA Astrophysics Data System (ADS)

Zhang, Xin; Cross, Jason B.; Romero, Jan; Heifetz, Alexander; Humphries, Eric; Hall, Katie; Wu, Yuchuan; Stucka, Sabrina; Zhang, Jing; Chandonnet, Haoqun; Lippa, Blaise; Ryan, M. Dominic; Baber, J. Christian

2018-03-01

Antagonism of CCR9 is a promising mechanism for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. There is limited experimental data on CCR9 and its ligands, complicating efforts to identify new small molecule antagonists. We present here results of a successful virtual screening and rational hit-to-lead campaign that led to the discovery and initial optimization of novel CCR9 antagonists. This work uses a novel data fusion strategy to integrate the output of multiple computational tools, such as 2D similarity search, shape similarity, pharmacophore searching, and molecular docking, as well as the identification and incorporation of privileged chemokine fragments. The application of various ranking strategies, which combined consensus and parallel selection methods to achieve a balance of enrichment and novelty, resulted in 198 virtual screening hits in total, with an overall hit rate of 18%. Several hits were developed into early leads through targeted synthesis and purchase of analogs.

The Promise of Antiretrovirals for HIV Prevention

PubMed Central

Flash, Charlene; Krakower, Douglas; Mayer, Kenneth H.

2013-01-01

With an estimated 2.6 million new HIV infections diagnosed annually, the world needs new prevention strategies to partner with condom use, harm reduction approaches for injection drug users, and male circumcision. Antiretrovirals can reduce the risk of mother-to-child HIV transmission and limit HIV acquisition after occupational exposure. Macaque models and clinical trials demonstrate efficacy of oral or topical antiretrovirals used prior to HIV exposure to prevent HIV transmission, ie pre-exposure prophylaxis (PrEP). Early initiation of effective HIV treatment in serodiscordant couples results in a 96% decrease in HIV transmission. HIV testing to determine serostatus and identify undiagnosed persons is foundational to these approaches. The relative efficacy of different approaches, adherence, cost and long-term safety will affect uptake and impact of these strategies. Ongoing research will help characterize the role for oral and topical formulations and help quantify potential benefits in sub-populations at risk for HIV acquisition. PMID:22351302

Molecular cues for development and regeneration of salivary glands

PubMed Central

Liu, Fei; Wang, Songlin

2015-01-01

The hypofunction of salivary glands caused by Sjögren’s Syndrome or radiotherapy for head and neck cancer significantly compromises the quality of life of millions patients. Currently no curative treatment is available for the irreversible hyposalivation, whereas regenerative strategies targeting salivary stem/progenitor cells are promising. However, the success of these strategies is constrained by the lack of insights on the molecular cues of salivary gland regeneration. Recent advances in the molecular controls of salivary gland morphogenesis provided valuable clues for identifying potential regenerative cues. A complicated network of signaling molecules between epithelia, mesenchyme, endothelia, extracellular matrix and innervating nerves orchestrate the salivary gland organogenesis. Here we discuss the roles of several cross-talking intercellular signaling pathways, i.e., FGF, Wnt, Hedgehog, Eda, Notch, Chrm1/HB-EGF and Laminin/Integrin pathways, in the development of salivary glands and their potentials to promote salivary regeneration. PMID:24189993

Bioremediation of uranium-contaminated groundwater: a systems approach to subsurface biogeochemistry.

PubMed

Williams, Kenneth H; Bargar, John R; Lloyd, Jonathan R; Lovley, Derek R

2013-06-01

Adding organic electron donors to stimulate microbial reduction of highly soluble U(VI) to less soluble U(IV) is a promising strategy for immobilizing uranium in contaminated subsurface environments. Studies suggest that diagnosing the in situ physiological status of the subsurface community during uranium bioremediation with environmental transcriptomic and proteomic techniques can identify factors potentially limiting U(VI) reduction activity. Models which couple genome-scale in silico representations of the metabolism of key microbial populations with geochemical and hydrological models may be able to predict the outcome of bioremediation strategies and aid in the development of new approaches. Concerns remain about the long-term stability of sequestered U(IV) minerals and the release of co-contaminants associated with Fe(III) oxides, which might be overcome through targeted delivery of electrons to select microorganisms using in situ electrodes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Disrupting beta-amyloid aggregation for Alzheimer disease treatment.

PubMed

Estrada, L D; Soto, C

2007-01-01

Alzheimer's disease is a devastating degenerative disorder for which there is no cure or effective treatment. Although the etiology of Alzheimer's disease is not fully understood, compelling evidence indicates that deposition of aggregates composed by a misfolded form of the amyloid beta peptide (Abeta) is the central event in the disease pathogenesis. Therefore, an attractive therapeutic strategy is to prevent or reverse Abeta misfolding and aggregation. Diverse strategies have been described to identify inhibitors of this process, including screening of libraries of small molecules chemical compounds, rational design of synthetic peptides, assessment of natural Abeta-binding proteins and stimulation of the immune system by vaccination. In this article we describe these different approaches, their principles and their potential strengths and weaknesses. Overall the available data suggest that the development of drugs to interfere with Abeta misfolding and aggregation is a feasible target that hold great promise for the treatment of Alzheimer's disease.

Elder Abuse: Global Situation, Risk Factors, and Prevention Strategies

PubMed Central

Pillemer, Karl; Burnes, David; Riffin, Catherine; Lachs, Mark S.

2016-01-01

Purpose: Elder mistreatment is now recognized internationally as a pervasive and growing problem, urgently requiring the attention of health care systems, social welfare agencies, policymakers, and the general public. In this article, we provide an overview of global issues in the field of elder abuse, with a focus on prevention. Design and Methods: This article provides a scoping review of key issues in the field from an international perspective. Results: By drawing primarily on population-based studies, this scoping review provided a more valid and reliable synthesis of current knowledge about prevalence and risk factors than has been available. Despite the lack of scientifically rigorous intervention research on elder abuse, the review also identified 5 promising strategies for prevention. Implications: The findings highlight a growing consensus across studies regarding the extent and causes of elder mistreatment, as well as the urgent need for efforts to make elder mistreatment prevention programs more effective and evidence based. PMID:26994260

Promising molecular targets and biomarkers for male BPH and LUTS.

PubMed

Gharaee-Kermani, Mehrnaz; Macoska, Jill A

2013-12-01

Benign prostatic hyperplasia (BPH) is a major health concern for aging men. BPH is associated with urinary voiding dysfunction and lower urinary tract symptoms (LUTS), which negatively affects quality of life. Surgical resection and medical approaches have proven effective for improving urinary flow and relieving LUTS but are not effective for all men and can produce adverse effects that require termination of the therapeutic regimen. Thus, there is a need to explore other therapeutic targets to treat BPH/LUTS. Complicating the treatment of BPH/LUTS is the lack of biomarkers to effectively identify pathobiologies contributing to BPH/LUTS or to gauge successful response to therapy. This review will briefly discuss current knowledge and will highlight new studies that illuminate the pathobiologies contributing to BPH/LUTS, potential new therapeutic strategies for successfully treating BPH/LUTS, and new approaches for better defining these pathobiologies and response to therapeutics through the development of biomarkers and phenotyping strategies.

Developing Informatics Tools and Strategies for Consumer-centered Health Communication

PubMed Central

Keselman, Alla; Logan, Robert; Smith, Catherine Arnott; Leroy, Gondy; Zeng-Treitler, Qing

2008-01-01

As the emphasis on individuals' active partnership in health care grows, so does the public's need for effective, comprehensible consumer health resources. Consumer health informatics has the potential to provide frameworks and strategies for designing effective health communication tools that empower users and improve their health decisions. This article presents an overview of the consumer health informatics field, discusses promising approaches to supporting health communication, and identifies challenges plus direction for future research and development. The authors' recommendations emphasize the need for drawing upon communication and social science theories of information behavior, reaching out to consumers via a range of traditional and novel formats, gaining better understanding of the public's health information needs, and developing informatics solutions for tailoring resources to users' needs and competencies. This article was written as a scholarly outreach and leadership project by members of the American Medical Informatics Association's Consumer Health Informatics Working Group. PMID:18436895

Oligonucleotide-based strategies to combat polyglutamine diseases

PubMed Central

Fiszer, Agnieszka; Krzyzosiak, Wlodzimierz J.

2014-01-01

Considerable advances have been recently made in understanding the molecular aspects of pathogenesis and in developing therapeutic approaches for polyglutamine (polyQ) diseases. Studies on pathogenic mechanisms have extended our knowledge of mutant protein toxicity, confirmed the toxicity of mutant transcript and identified other toxic RNA and protein entities. One very promising therapeutic strategy is targeting the causative gene expression with oligonucleotide (ON) based tools. This straightforward approach aimed at halting the early steps in the cascade of pathogenic events has been widely tested for Huntington's disease and spinocerebellar ataxia type 3. In this review, we gather information on the use of antisense oligonucleotides and RNA interference triggers for the experimental treatment of polyQ diseases in cellular and animal models. We present studies testing non-allele-selective and allele-selective gene silencing strategies. The latter include targeting SNP variants associated with mutations or targeting the pathologically expanded CAG repeat directly. We compare gene silencing effectors of various types in a number of aspects, including their design, efficiency in cell culture experiments and pre-clinical testing. We discuss advantages, current limitations and perspectives of various ON-based strategies used to treat polyQ diseases. PMID:24848018

Reducing Aggressive Male Behavior in Elementary School: Promising Practices

ERIC Educational Resources Information Center

Holmes, Barbara; Gibson, Jamel; Morrison-Danner, Dietrich

2014-01-01

Student aggression and violent behavior, especially among males, is pervasive and problematic in the classroom. When incorporated in the lesson design, promising practices (music, movement, and visual stimulation) are evidence-based strategies that may reduce male aggression in the classroom.

Using the CRA-I Strategy to Develop Conceptual and Procedural Knowledge of Quadratic Expressions

ERIC Educational Resources Information Center

Strickland, Tricia K.

2016-01-01

Recent research has explored the efficacy of the CRA-I (concrete-representational-abstract) strategy with students with disabilities (Strickland & Maccini, 2012, 2013). The CRA-I strategy is a promising practice that special educators have used to teach algebra to students with high-incidence disabilities. The CRA-I strategy is a modification…

Program Implementation Approaches to Build and Sustain Health Care Coordination for Type 2 Diabetes.

PubMed

Fitzgerald, Tania M; Williams, Pam A; Dodge, Julia A; Quinn, Martha; Heminger, Christina L; Moultrie, Rebecca; Taylor, Olivia; Nelson, Belinda W; Lewis, Megan A

2017-03-01

As more people enter the U.S. health care system under the Affordable Care Act (ACA), it is increasingly critical to deliver coordinated, high-quality health care. The ACA supports implementation and sustainability of efficient health care models, given expected limits in available resources. This article highlights implementation strategies to build and sustain care coordination, particularly ones consistent with and reinforced by the ACA. It focuses on disease self-management programs to improve the health of patients with type 2 diabetes, exemplified by grantees of the Alliance to Reduce Disparities in Diabetes. We conducted interviews with grantee program representatives throughout their 5-year programs and conducted a qualitative framework analysis of data to identify key themes related to care coordination. The most promising care coordination strategies that grantee programs described included establishing clinic-community collaborations, embedding community health workers within care management teams, and sharing electronic data. Establishing provider buy-in was crucial for these strategies to be effective. This article adds new insights into strategies promoting effective care coordination. The strategies that grantees implemented throughout the program align with ACA requirements, underscoring their relevance to the changing U.S. health care environment and the likelihood of further support for program sustainability.

Strategies to improve health coverage and narrow the equity gap in child survival, health, and nutrition.

PubMed

Chopra, Mickey; Sharkey, Alyssa; Dalmiya, Nita; Anthony, David; Binkin, Nancy

2012-10-13

Implementation of innovative strategies to improve coverage of evidence-based interventions, especially in the most marginalised populations, is a key focus of policy makers and planners aiming to improve child survival, health, and nutrition. We present a three-step approach to improvement of the effective coverage of essential interventions. First, we identify four different intervention delivery channels--ie, clinical or curative, outreach, community-based preventive or promotional, and legislative or mass media. Second, we classify which interventions' deliveries can be improved or changed within their channel or by switching to another channel. Finally, we do a meta-review of both published and unpublished reviews to examine the evidence for a range of strategies designed to overcome supply and demand bottlenecks to effective coverage of interventions that improve child survival, health, and nutrition. Although knowledge gaps exist, several strategies show promise for improving coverage of effective interventions-and, in some cases, health outcomes in children-including expanded roles for lay health workers, task shifting, reduction of financial barriers, increases in human-resource availability and geographical access, and use of the private sector. Policy makers and planners should be informed of this evidence as they choose strategies in which to invest their scarce resources. Copyright © 2012 Elsevier Ltd. All rights reserved.

Promising medications for cocaine dependence treatment.

PubMed

Somaini, Lorenzo; Donnini, Claudia; Raggi, Maria A; Amore, Mario; Ciccocioppo, Roberto; Saracino, Maria A; Kalluppi, Marsida; Malagoli, Marco; Gerra, Maria L; Gerra, Gilberto

2011-05-01

Cocaine dependence is characterized by compulsive drug seeking and high vulnerability to relapse. Overall, cocaine remains one of the most used illicit drugs in the world. Given the difficulty of achieving sustained recovery, pharmacotherapy of cocaine addiction remains one of the most important clinical challenges. Recent advances in neurobiology, brain imaging and clinical trials suggest that certain medications show promise in the treatment of cocaine addiction. The pharmacotherapeutic approaches for cocaine dependence include medications able to target specific subtypes of dopamine receptors, affect different neurotransmitter systems (i.e. noradrenergic, serotonergic, cholinergic, glutamatergic, GABAergic and opioidergic pathways), and modulate neurological processes. The systematic reviews concerning the pharmacological treatment of cocaine dependence appear to indicate controversial findings and inconclusive results. The aim of future studies should be to identify the effective medications matching the specific needs of patients with specific characteristics, abandoning the strategies extended to the entire population of cocaine dependent patients. In the present review we summarize the current pharmacotherapeutic approaches to the treatment of cocaine dependence with a focus on the new patents.

Two- and three-dimensional folding of thin film single-crystalline silicon for photovoltaic power applications

PubMed Central

Guo, Xiaoying; Li, Huan; Yeop Ahn, Bok; Duoss, Eric B.; Hsia, K. Jimmy; Lewis, Jennifer A.; Nuzzo, Ralph G.

2009-01-01

Fabrication of 3D electronic structures in the micrometer-to-millimeter range is extremely challenging due to the inherently 2D nature of most conventional wafer-based fabrication methods. Self-assembly, and the related method of self-folding of planar patterned membranes, provide a promising means to solve this problem. Here, we investigate self-assembly processes driven by wetting interactions to shape the contour of a functional, nonplanar photovoltaic (PV) device. A mechanics model based on the theory of thin plates is developed to identify the critical conditions for self-folding of different 2D geometrical shapes. This strategy is demonstrated for specifically designed millimeter-scale silicon objects, which are self-assembled into spherical, and other 3D shapes and integrated into fully functional light-trapping PV devices. The resulting 3D devices offer a promising way to efficiently harvest solar energy in thin cells using concentrator microarrays that function without active light tracking systems. PMID:19934059

Emerging Role of MicroRNAs as Liquid Biopsy Biomarkers in Gastrointestinal Cancers

PubMed Central

Shigeyasu, Kunitoshi; Toden, Shusuke; Zumwalt, Timothy J.; Okugawa, Yoshinaga; Goel, Ajay

2017-01-01

Cancer has emerged as a leading cause of mortality worldwide, claiming over 8 million lives annually. Gastrointestinal (GI) cancers account for ~35% of these mortalities. Recent advances in diagnostic and treatment strategies have reduced mortality among GI cancer patients, yet a significant number of patients still develop late-stage cancer, where treatment options are inadequate. Emerging interests in ‘liquid biopsies’ have encouraged investigators to identify and develop clinically-relevant noninvasive genomic and epigenomic signatures that can be exploited as biomarkers capable of detecting premalignant and early-stage cancers. In this context, microRNAs (miRNAs), which are small non-coding RNAs that are frequently dysregulated in cancers, have emerged as promising entities for such diagnostic purposes. Albeit the future looks promising, current approaches for detecting miRNAs in blood and other biofluids remain inadequate. This review summarizes existing efforts to exploit circulating miRNAs as cancer biomarkers, evaluates their potential and challenges as liquid biopsy-based biomarkers for GI cancers. PMID:28143873

Targeting Notch signalling pathway of cancer stem cells.

PubMed

Venkatesh, Vandana; Nataraj, Raghu; Thangaraj, Gopenath S; Karthikeyan, Murugesan; Gnanasekaran, Ashok; Kaginelli, Shanmukhappa B; Kuppanna, Gobianand; Kallappa, Chandrashekrappa Gowdru; Basalingappa, Kanthesh M

2018-01-01

Cancer stem cells (CSCs) have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. CSCs have been increasingly identified in blood cancer, prostate, ovarian, lung, melanoma, pancreatic, colon, brain and many more malignancies. CSCs have slow growth rate and are resistant to chemotherapy and radiotherapy that lead to the failure of traditional current therapy. Eradicating the CSCs and recurrence, is promising aspect for the cure of cancer. The CSCs like any other stem cells activate the signal transduction pathways that involve the development and tissue homeostasis, which include Notch signaling pathway. The new treatment targets these pathway that control stem-cell replication, survival and differentiation that are under development. Notch inhibitors either single or in combination with chemotherapy drugs have been developed to treat cancer and its recurrence. This approach of targeting signaling pathway of CSCs represents a promising future direction for the therapeutic strategy to cure cancer.

[Acute myeloid leukemia. Genetic diagnostics and molecular therapy].

PubMed

Schlenk, R F; Döhner, K; Döhner, H

2013-02-01

Acute myeloid leukemia (AML) is a genetically heterogeneous disease. The genetic diagnostics have become an essential component in the initial work-up for disease classification, prognostication and prediction. More and more promising molecular targeted therapeutics are becoming available. A prerequisite for individualized treatment strategies is a fast pretherapeutic molecular screening including the fusion genes PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11 as well as mutations in the genes NPM1, FLT3 and CEBPA. Promising new therapeutic approaches include the combination of all- trans retinoic acid and arsentrioxid in acute promyelocytic leukemia, the combination of intensive chemotherapy with KIT inhibitors in core-binding factor AML and FLT3 inhibitors in AML with FLT3 mutation, as well as gemtuzumab ozogamicin therapy in patients with low and intermediate cytogenetic risk profiles. With the advent of the next generation sequencing technologies it is expected that new therapeutic targets will be identified. These insights will lead to a further individualization of AML therapy.

Discovering Collaboration and Knowledge Management Practices for the Future Digital Factory

NASA Astrophysics Data System (ADS)

Flores, Myrna; Vera, Tomas; Tucci, Christopher

Recently there has been an explosion of new technologies and tools such as wikis, blogs, tags, Facebook, among many others, that are commonly identified under Web 2.0 and which promise a new digital business ecosystem fed by formal/informal and internal/external relationships and interactions. Although Web 2.0 is very promising to enable such collective knowledge creation, technology by itself is not the only ingredient. It is also required to define the right strategy, governance, culture, processes, training, incentives among others, before implementing such innovative open spaces for collaboration and knowledge sharing. Therefore, the objective of this paper is to present a Knowledge Management (KM) Framework and a Maturity Model developed by a CEMEX and EPFL collaborative research project to discover the AS-IS collaboration practices in CEMEX before the implementation of the SMARTBRICKS Web 2.0 prototype for Business Process Management (BPM), currently under development by the Intelligent Manufacturing Systems (IMS) Swiss Digital Factory (DiFac) project.

Facilitating Racial and Ethnic Diversity in the Health Workforce.

PubMed

Snyder, Cyndy R; Frogner, Bianca K; Skillman, Susan M

2018-01-01

Racial and ethnic diversity in the health workforce can facilitate access to healthcare for underserved populations and meet the health needs of an increasingly diverse population. In this study, we explored 1) changes in the racial and ethnic diversity of the health workforce in the United States over the last decade, and 2) evidence on the effectiveness of programs designed to promote racial and ethnic diversity in the U.S. health workforce. Findings suggest that although the health workforce overall is becoming more diverse, people of color are most often represented among the entry-level, lower-skilled health occupations. Promising practices to help facilitate diversity in the health professions were identified in the literature, namely comprehensive programs that integrated multiple interventions and strategies. While some efforts have been found to be promising in increasing the interest, application, and enrollment of racial and ethnic minorities into health profession schools, there is still a missing link in understanding persistence, graduation, and careers.

Two- and three-dimensional folding of thin film single-crystalline silicon for photovoltaic power applications.

PubMed

Guo, Xiaoying; Li, Huan; Ahn, Bok Yeop; Duoss, Eric B; Hsia, K Jimmy; Lewis, Jennifer A; Nuzzo, Ralph G

2009-12-01

Fabrication of 3D electronic structures in the micrometer-to-millimeter range is extremely challenging due to the inherently 2D nature of most conventional wafer-based fabrication methods. Self-assembly, and the related method of self-folding of planar patterned membranes, provide a promising means to solve this problem. Here, we investigate self-assembly processes driven by wetting interactions to shape the contour of a functional, nonplanar photovoltaic (PV) device. A mechanics model based on the theory of thin plates is developed to identify the critical conditions for self-folding of different 2D geometrical shapes. This strategy is demonstrated for specifically designed millimeter-scale silicon objects, which are self-assembled into spherical, and other 3D shapes and integrated into fully functional light-trapping PV devices. The resulting 3D devices offer a promising way to efficiently harvest solar energy in thin cells using concentrator microarrays that function without active light tracking systems.

Realizing the promise of social psychology in improving public health.

PubMed

Klein, William M P; Shepperd, James A; Suls, Jerry; Rothman, Alexander J; Croyle, Robert T

2015-02-01

The theories, phenomena, empirical findings, and methodological approaches that characterize contemporary social psychology hold much promise for addressing enduring problems in public health. Indeed, social psychologists played a major role in the development of the discipline of health psychology during the 1970s and 1980s. The health domain allows for the testing, refinement, and application of many interesting and important research questions in social psychology, and offers the discipline a chance to enhance its reach and visibility. Nevertheless, in a review of recent articles in two major social-psychological journals (Personality and Social Psychology Bulletin and Journal of Personality and Social Psychology), we found that only 3.2% of 467 studies explored health-related topics. In this article, we identify opportunities for research at the interface of social psychology and health, delineate barriers, and offer strategies that can address these barriers as the discipline continues to evolve. © 2014 by the Society for Personality and Social Psychology, Inc.

Medicinal plants--prophylactic and therapeutic options for gastrointestinal and respiratory diseases in calves and piglets? A systematic review.

PubMed

Ayrle, Hannah; Mevissen, Meike; Kaske, Martin; Nathues, Heiko; Gruetzner, Niels; Melzig, Matthias; Walkenhorst, Michael

2016-06-06

Gastrointestinal and respiratory diseases in calves and piglets lead to significant economic losses in livestock husbandry. A high morbidity has been reported for diarrhea (calves ≤ 35%; piglets ≤ 50%) and for respiratory diseases (calves ≤ 80%; piglets ≤ 40%). Despite a highly diverse etiology and pathophysiology of these diseases, treatment with antimicrobials is often the first-line therapy. Multi-antimicrobial resistance in pathogens results in international accordance to strengthen the research in novel treatment options. Medicinal plants bear a potential as alternative or additional treatment. Based on the versatile effects of their plant specific multi-component-compositions, medicinal plants can potentially act as 'multi-target drugs'. Regarding the plurality of medicinal plants, the aim of this systematic review was to identify potential medicinal plant species for prevention and treatment of gastrointestinal and respiratory diseases and for modulation of the immune system and inflammation in calves and piglets. Based on nine initial sources including standard textbooks and European ethnoveterinary studies, a total of 223 medicinal plant species related to the treatment of gastrointestinal and respiratory diseases was identified. A defined search strategy was established using the PRISMA statement to evaluate 30 medicinal plant species starting from 20'000 peer-reviewed articles published in the last 20 years (1994-2014). This strategy led to 418 references (257 in vitro, 84 in vivo and 77 clinical trials, thereof 48 clinical trials in veterinary medicine) to evaluate effects of medicinal plants and their efficacy in detail. The findings indicate that the most promising candidates for gastrointestinal diseases are Allium sativum L., Mentha x piperita L. and Salvia officinalis L.; for diseases of the respiratory tract Echinacea purpurea (L.) MOENCH, Thymus vulgaris L. and Althea officinalis L. were found most promising, and Echinacea purpurea (L.) MOENCH, Camellia sinensis (L.) KUNTZE, Glycyrrhiza glabra L. and Origanum vulgare L. were identified as best candidates for modulation of the immune system and inflammation. Several medicinal plants bear a potential for novel treatment strategies for young livestock. There is a need for further research focused on gastrointestinal and respiratory diseases in calves and piglets, and the findings of this review provide a basis on plant selection for future studies.

Therapeutic options for diseases due to potential viral agents of bioterrorism.

PubMed

Bronze, Michael S; Greenfield, Ronald A

2003-02-01

The etiologic agents of smallpox and viral hemorrhagic fever have emerged as potential agents of bioterrorism due to their virulence, potential for human to human dissemination and limited strategies for treatment and prevention. Cidofovir has shown significant promise in animal models, and limited case reports in humans are encouraging. Ribavirin is the treatment of choice for certain hemorrhagic fever viral infections, but has no current application to Ebola and Marburg infections. Current vaccine strategies for smallpox are effective, but carry significant risk for complications. Licensed vaccines for hemorrhagic fever viruses are limited to yellow fever, but animal studies are promising. Genomic analysis of the viral pathogen and the animal model response to infection may provide valuable information enabling the development of novel treatment and prevention strategies. Current knowledge of these strategies is reviewed.

Success rates for product development strategies in new drug development.

PubMed

Dahlin, E; Nelson, G M; Haynes, M; Sargeant, F

2016-04-01

While research has examined the likelihood that drugs progress across phases of clinical trials, no research to date has examined the types of product development strategies that are the most likely to be successful in clinical trials. This research seeks to identify the strategies that are most likely to reach the market-those generated using a novel product development strategy or strategies that combine a company's expertise with both drugs and indications, which we call combined experience strategies. We evaluate the success of product development strategies in the drug development process for a sample of 2562 clinical trials completed by 406 US pharmaceutical companies. To identify product development strategies, we coded each clinical trial according to whether it consisted of an indication or a drug that was new to the firm. Accordingly, a clinical trial that consists of both an indication and a drug that were both new to the firm represents a novel product development strategy; indication experience is a product development strategy that consists of an indication that a firm had tested previously in a clinical trial, but with a drug that was new to the firm; drug experience is a product development strategy that consists of a drug that the firm had prior experience testing in clinical trials, but with an indication that was new to the firm; combined experience consists of both a drug and an indication that the firm had experience testing in clinical trials. Success rates for product development strategies across clinical phases were calculated for the clinical trials in our sample. Combined experience strategies had the highest success rate. More than three and a half percent (0·036) of the trials that combined experience with drugs and indications eventually reached the market. The next most successful strategy is drug experience (0·025) with novel strategies trailing closely (0·024). Indication experience strategies are the least successful (0·008). These differences are statistically significant. The primary contribution of this study is that product development strategies combining experience with drugs and indications strategies are the most likely to reach the market, even though they are least common strategy. Therefore, combined experience strategies remain underutilized. The findings also suggest a promising path for pursuing combined experience strategies: gaining expertise with drugs is likely to be a more effective path to gaining the expertise necessary for developing subsequent recombination strategies. © 2016 John Wiley & Sons Ltd.

Whole organism high content screening identifies stimulators of pancreatic beta-cell proliferation.

PubMed

Tsuji, Naoki; Ninov, Nikolay; Delawary, Mina; Osman, Sahar; Roh, Alex S; Gut, Philipp; Stainier, Didier Y R

2014-01-01

Inducing beta-cell mass expansion in diabetic patients with the aim to restore glucose homeostasis is a promising therapeutic strategy. Although several in vitro studies have been carried out to identify modulators of beta-cell mass expansion, restoring endogenous beta-cell mass in vivo has yet to be achieved. To identify potential stimulators of beta-cell replication in vivo, we established transgenic zebrafish lines that monitor and allow the quantification of cell proliferation by using the fluorescent ubiquitylation-based cell cycle indicator (FUCCI) technology. Using these new reagents, we performed an unbiased chemical screen, and identified 20 small molecules that markedly increased beta-cell proliferation in vivo. Importantly, these structurally distinct molecules, which include clinically-approved drugs, modulate three specific signaling pathways: serotonin, retinoic acid and glucocorticoids, showing the high sensitivity and robustness of our screen. Notably, two drug classes, retinoic acid and glucocorticoids, also promoted beta-cell regeneration after beta-cell ablation. Thus, this study establishes a proof of principle for a high-throughput small molecule-screen for beta-cell proliferation in vivo, and identified compounds that stimulate beta-cell proliferation and regeneration.

Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells.

PubMed

Johannessen, Liv; Sundberg, Thomas B; O'Connell, Daniel J; Kolde, Raivo; Berstler, James; Billings, Katelyn J; Khor, Bernard; Seashore-Ludlow, Brinton; Fassl, Anne; Russell, Caitlin N; Latorre, Isabel J; Jiang, Baishan; Graham, Daniel B; Perez, Jose R; Sicinski, Piotr; Phillips, Andrew J; Schreiber, Stuart L; Gray, Nathanael S; Shamji, Alykhan F; Xavier, Ramnik J

2017-10-01

Enhancing production of the anti-inflammatory cytokine interleukin-10 (IL-10) is a promising strategy to suppress pathogenic inflammation. To identify new mechanisms regulating IL-10 production, we conducted a phenotypic screen for small molecules that enhance IL-10 secretion from activated dendritic cells. Mechanism-of-action studies using a prioritized hit from the screen, BRD6989, identified the Mediator-associated kinase CDK8, and its paralog CDK19, as negative regulators of IL-10 production during innate immune activation. The ability of BRD6989 to upregulate IL-10 is recapitulated by multiple, structurally differentiated CDK8 and CDK19 inhibitors and requires an intact cyclin C-CDK8 complex. Using a highly parallel pathway reporter assay, we identified a role for enhanced AP-1 activity in IL-10 potentiation following CDK8 and CDK19 inhibition, an effect associated with reduced phosphorylation of a negative regulatory site on c-Jun. These findings identify a function for CDK8 and CDK19 in regulating innate immune activation and suggest that these kinases may warrant consideration as therapeutic targets for inflammatory disorders.

Biodegradation of plastics: current scenario and future prospects for environmental safety.

PubMed

Ahmed, Temoor; Shahid, Muhammad; Azeem, Farrukh; Rasul, Ijaz; Shah, Asad Ali; Noman, Muhammad; Hameed, Amir; Manzoor, Natasha; Manzoor, Irfan; Muhammad, Sher

2018-03-01

Plastic is a general term used for a wide range of high molecular weight organic polymers obtained mostly from the various hydrocarbon and petroleum derivatives. There is an ever-increasing trend towards the production and consumption of plastics due to their extensive industrial and domestic applications. However, a wide spectrum of these polymers is non-biodegradable with few exceptions. The extensive use of plastics, lack of waste management, and casual community behavior towards their proper disposal pose a significant threat to the environment. This has raised growing concerns among various stakeholders to devise policies and innovative strategies for plastic waste management, use of biodegradable polymers especially in packaging, and educating people for their proper disposal. Current polymer degradation strategies rely on chemical, thermal, photo, and biological procedures. In the presence of proper waste management strategies coupled with industrially controlled biodegradation facilities, the use of biodegradable plastics for some applications such as packaging or health industry is a promising and attractive option for economic, environmental, and health benefits. This review highlights the classification of plastics with special emphasis on biodegradable plastics and their rational use, the identified mechanisms of plastic biodegradation, the microorganisms involved in biodegradation, and the current insights into the research on biodegradable plastics. The review has also identified the research gaps in plastic biodegradation followed by future research directions.

Detection strategies for the first supernovae with JWST

NASA Astrophysics Data System (ADS)

Hartwig, Tilman; Bromm, Volker; Loeb, Abraham

2018-06-01

Pair-instability supernovae (PISNe) are very luminous explosions of massive, low metallicity stars. They can potentially be observed out to high redshifts due to their high explosion energies, thus providing a probe of the Universe prior to reionization. The near-infrared camera, NIRCam, on board the James Webb Space Telescope is ideally suited for detecting their redshifted ultraviolet emission. We calculate the photometric signature of high-redshift PISNe and derive the optimal detection strategy for identifying their prompt emission and possible afterglow. We differentiate between PISNe and other sources that could have a similar photometric signature, such as active galactic nuclei or high-redshift galaxies. We demonstrate that the optimal strategy, which maximizes the visibility time of the PISN lightcurve per invested exposure time, consists of the two wide-band filters F200W and F356W with an exposure time of 600 s. For such exposures, we expect one PISN at z ≲ 7.5 per at least 50,000 different field of view, which can be accomplished with parallel observations and an extensive archival search. The PISN afterglow, caused by nebular emission and reverberation, is very faint and requires unfeasibly long exposure times to be uniquely identified. However, this afterglow would be visible for several hundred years, about two orders of magnitude longer than the prompt emission, rendering PISNe promising targets for future, even more powerful telescopes.

The Integrated Scorecard in support of corporate sustainability strategies.

PubMed

Journeault, Marc

2016-11-01

Organizations have increasingly recognized the importance and benefits of developing a sustainability strategy that incorporates environmental and social responsibilities. However, the simultaneous integration of the economic, environmental and social aspects remains a major concern for organizations. The Sustainability Balanced Scorecard (SBSC) represents one of the most promising strategic tools to help organizations face these challenges and support their sustainability strategy. However, past research has provided unclear, incomplete and even contradictory SBSC frameworks while offering little knowledge about how to integrate stakeholder management as well as environmental and social performance within the balanced scorecard to successfully support a corporate sustainability strategy. The aim of this study is to address these issues and limitations by proposing the Integrated Scorecard, a specific SBSC that integrates the three pillars of sustainability performance within four different perspectives, namely environmental, social and economic performance, stakeholder management, internal business processes, and skills and capabilities. This study provides a conceptual approach to the Integrated Scorecard and illustrates, through the use of two practical illustrations, the ability of this framework to support the corporate sustainability strategy by identifying the core sustainability objectives that organizations should achieve when creating value, facilitating the understanding of the contribution of environmental and social initiatives on economic performance, allowing the monitoring and measurement of the strategy's level of achievement, and creating synergy between sustainability performance management and reporting. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biosensor commercialization strategy - a theoretical approach.

PubMed

Lin, Chin-Tsai; Wang, Su-Man

2005-01-01

Biosensors are analytical devices, which use biological interactions to provide either qualitative or quantitative results. They are extensively employed in many fields such as clinical diagnosis and biomedicine, military applications, anti-terrorism, farm, garden and veterinary analysis, process control, fermentation control and analysis, pharmaceutical and drug analysis, food and drink production and analysis, pollution control and monitoring, microbiology, bacterial and viral analysis, mining, and industrial and toxic gases. The biosensor market has significantly increased and will be mushrooming in the next decade. The total biosensor market is estimated to be 10.8 billion dollars by 2007. The emerging biosensor market presents both opportunities and obstacles to start-up biosensor entrepreneurs. The major challenge and threat for these entrepreneurs is how to predict the biosensor market and how to convert promising biosensor technology into commercialized biosensors. By adopting a simple commercialization strategy framework, we identify two key elements of biosensor commercialization strategy: excludability and complementary asset. We further divide biosensor commercialization environments into four distinct sub-environments: the Attacker's Advantage, Reputation-Based Idea Trading, Greenfield Competition and Ideas Factories. This paper explains how the interaction between these two key elements shapes biosensor commercialization strategy and biosensor industry dynamics. This paper also discusses alternative commercialization strategies for each specific commercialization environment and how to choose from these alternatives. The analysis of this study further provides a good reference for start-up biosensor entrepreneurs to formulate effective biosensor commercialization strategy.

78 FR 27220 - EPA Activities To Promote Environmental Justice in the Permit Application Process

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-09

... overarching strategy for advancing environmental justice. The Plan has three goals: 1. Protect health and the... recommended some of the outreach strategies included in Promising Practices previously. Nevertheless, EPA... experience to develop strategies tailored to the particular communities and needs within that region. Thus...

Lotta Lara: A Promising Biliterate Reading Strategy

ERIC Educational Resources Information Center

Butvilofsky, Sandra A.; Sparrow, Wendy; Roberson, Nathan D.; Hopewell, Susan

2017-01-01

This quasi-experimental study tested the efficacy of a research based biliterate reading strategy, Lotta Lara, that is part of a larger paired literacy instructional program. Its purpose was to investigate whether the biliterate reading strategy, which focuses on reading fluency, comprehension, and oracy through whole group instruction, impacted…

Decreasing nitrate-N loads to coastal ecosystems with innovative drainage management strategies in agricultural landscapes: An experimental approach

USDA-ARS?s Scientific Manuscript database

Controlled drainage in agricultural ditches contributes to a drainage management strategy with potential environmental and production benefits. Innovative drainage strategies including spatially orientated low-grade weirs show promise to significantly improve nutrient (e.g. nitrate-N) reductions by...

Economic Outcomes With Anatomical Versus Functional Diagnostic Testing for Coronary Artery Disease.

PubMed

Mark, Daniel B; Federspiel, Jerome J; Cowper, Patricia A; Anstrom, Kevin J; Hoffmann, Udo; Patel, Manesh R; Davidson-Ray, Linda; Daniels, Melanie R; Cooper, Lawton S; Knight, J David; Lee, Kerry L; Douglas, Pamela S

2016-07-19

PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) found that initial use of at least 64-slice multidetector computed tomography angiography (CTA) versus functional diagnostic testing strategies did not improve clinical outcomes in stable symptomatic patients with suspected coronary artery disease (CAD) requiring noninvasive testing. To conduct an economic analysis for PROMISE (a major secondary aim of the study). Prospective economic study from the U.S. perspective. Comparisons were made according to the intention-to-treat principle, and CIs were calculated using bootstrap methods. (ClinicalTrials.gov: NCT01174550). 190 U.S. centers. 9649 U.S. patients enrolled in PROMISE between July 2010 and September 2013. Median follow-up was 25 months. Technical costs of the initial (outpatient) testing strategy were estimated from Premier Research Database data. Hospital-based costs were estimated using hospital bills and Medicare cost-charge ratios. Physician fees were taken from the Medicare Physician Fee Schedule. Costs were expressed in 2014 U.S. dollars, discounted at 3% annually, and estimated out to 3 years using inverse probability weighting methods. The mean initial testing costs were $174 for exercise electrocardiography; $404 for CTA; $501 to $514 for pharmacologic and exercise stress echocardiography, respectively; and $946 to $1132 for exercise and pharmacologic stress nuclear testing, respectively. Mean costs at 90 days were $2494 for the CTA strategy versus $2240 for the functional strategy (mean difference, $254 [95% CI, -$634 to $906]). The difference was associated with more revascularizations and catheterizations (4.25 per 100 patients) with CTA use. After 90 days, the mean cost difference between the groups out to 3 years remained small. Cost weights for test strategies were obtained from sources outside PROMISE. Computed tomography angiography and functional diagnostic testing strategies in patients with suspected CAD have similar costs through 3 years of follow-up. National Heart, Lung, and Blood Institute.

Progress and Future Directions in Research on the Psychosis Prodrome: A Review for Clinicians

PubMed Central

Woodberry, Kristen A; Shapiro, Daniel I; Bryant, Caitlin; Seidman, Larry J.

2016-01-01

The psychosis prodrome, or period of clinical and functional decline leading up to acute psychosis, offers a unique opportunity for identifying mechanisms of psychosis onset and testing early intervention strategies. We summarize major findings and emerging directions in prodromal research and provide recommendations for clinicians working with individuals suspected to be at high risk for psychosis. The past two decades of research have led to three major advances. First, tools and criteria have been developed that can reliably identify imminent risk for a psychotic disorder. Second, longitudinal clinical and psychobiological data from large multisite studies are strengthening individual risk assessment and offering insights into potential mechanisms of illness onset. Third, psychosocial and pharmacological interventions are demonstrating promise for delaying or preventing the onset of psychosis in help-seeking, high-risk individuals. The dynamic psychobiological processes implicated in both risk and onset of psychosis, including altered gene expression, cognitive dysfunction, inflammation, gray and white matter brain changes, and vulnerability-stress interactions suggest a wide range of potential treatment targets and strategies. The expansion of resources devoted to early intervention and prodromal research worldwide raises hope for investigating them. Future directions include identifying psychosis-specific risk and resilience factors in children, adolescents, and non-help-seeking community samples, improving study designs to test hypothesized mechanisms of change, and intervening with strategies that better engage youth, their environmental contexts, and neurodevelopmental targets to improve functional outcomes. Prospective research on putatively prodromal samples has the potential to substantially reshape our understanding of mental illness and our efforts to combat it. PMID:26954594

Trends in mass spectrometry instrumentation for proteomics

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

Smith, Richard D.

2002-12-01

Mass spectrometry has become a primary tool for proteomics due to its capabilities for rapid and sensitive protein identification and quantitation. It is now possible to identify thousands of proteins from microgram sample quantities in a single day and to quantify relative protein abundances. However, the needs for increased capabilities for proteome measurements are immense and are now driving both new strategies and instrument advances. These developments include those based on integration with multi-dimensional liquid separations and high accuracy mass measurements, and promise more than order of magnitude improvements in sensitivity, dynamic range, and throughput for proteomic analyses in themore » near future.« less

Domestication and Breeding of Jatropha curcas L.

PubMed

Montes, Juan M; Melchinger, Albrecht E

2016-12-01

Jatropha curcas L. (jatropha) has a high, untapped potential to contribute towards sustainable production of food and bioenergy, rehabilitation of degraded land, and reduction of atmospheric carbon dioxide. Tremendous progress in jatropha domestication and breeding has been achieved during the past decade. This review: (i) summarizes current knowledge about the domestication and breeding of jatropha; (ii) identifies and prioritizes areas for further research; and (iii) proposes strategies to exploit the full genetic potential of this plant species. Altogether, the outlook is promising for accelerating the domestication of jatropha by applying modern scientific methods and novel technologies developed in plant breeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

Joint fMRI analysis and subject clustering using sparse dictionary learning

NASA Astrophysics Data System (ADS)

Kim, Seung-Jun; Dontaraju, Krishna K.

2017-08-01

Multi-subject fMRI data analysis methods based on sparse dictionary learning are proposed. In addition to identifying the component spatial maps by exploiting the sparsity of the maps, clusters of the subjects are learned by postulating that the fMRI volumes admit a subspace clustering structure. Furthermore, in order to tune the associated hyper-parameters systematically, a cross-validation strategy is developed based on entry-wise sampling of the fMRI dataset. Efficient algorithms for solving the proposed constrained dictionary learning formulations are developed. Numerical tests performed on synthetic fMRI data show promising results and provides insights into the proposed technique.

Mixotrophic cultivation of microalgae for biodiesel production: status and prospects.

PubMed

Wang, Jinghan; Yang, Haizhen; Wang, Feng

2014-04-01

Biodiesel from microalgae provides a promising alternative for biofuel production. Microalgae can be produced under three major cultivation modes, namely photoautotrophic cultivation, heterotrophic cultivation, and mixotrophic cultivation. Potentials and practices of biodiesel production from microalgae have been demonstrated mostly focusing on photoautotrophic cultivation; mixotrophic cultivation of microalgae for biodiesel production has rarely been reviewed. This paper summarizes the mechanisms and virtues of mixotrophic microalgae cultivation through comparison with other major cultivation modes. Influencing factors of microalgal biodiesel production under mixotrophic cultivation are presented, development of combining microalgal biodiesel production with wastewater treatment is especially reviewed, and bottlenecks and strategies for future commercial production are also identified.

Family-focused physical activity, diet and obesity interventions in African-American girls: a systematic review.

PubMed

Barr-Anderson, D J; Adams-Wynn, A W; DiSantis, K I; Kumanyika, S

2013-01-01

Obesity interventions that involve family members may be effective with racial/ethnic minority youth. This review assessed the nature and effectiveness of family involvement in obesity interventions among African-American girls aged 5-18 years, a population group with high rates of obesity. Twenty-six databases were searched between January 2011 and March 2012, yielding 27 obesity pilot or full-length prevention or treatment studies with some degree of family involvement and data specific to African-American girls. Interventions varied in type and level of family involvement, cultural adaptation, delivery format and behaviour change intervention strategies; most targeted parent-child dyads. Some similarities in approach based on family involvement were identified. The use of theoretical perspectives specific to African-American family dynamics was absent. Across all studies, effects on weight-related behaviours were generally promising but often non-significant. Similar conclusions were drawn for weight-related outcomes among the full-length randomized controlled trials. Many strategies appeared promising on face value, but available data did not permit inferences about whether or how best to involve family members in obesity prevention and treatment interventions with African-American girls. Study designs that directly compare different types and levels of family involvement and incorporate relevant theoretical elements may be an important next step. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

Probiotics and gastrointestinal disease: successes, problems and future prospects

PubMed Central

2009-01-01

Gastrointestinal disease is a major cause of morbidity and mortality worldwide each year. Treatment of chronic inflammatory gastrointestinal conditions such as ulcerative colitis and Crohn's disease is difficult due to the ambiguity surrounding their precise aetiology. Infectious gastrointestinal diseases, such as various types of diarrheal disease are also becoming increasingly difficult to treat due to the increasing dissemination of antibiotic resistance among microorganisms and the emergence of the so-called 'superbugs'. Taking into consideration these problems, the need for novel therapeutics is essential. Although described for over a century probiotics have only been extensively researched in recent years. Their use in the treatment and prevention of disease, particularly gastrointestinal disease, has yielded many successful results, some of which we outline in this review. Although promising, many probiotics are hindered by inherent physiological and technological weaknesses and often the most clinically promising strains are unusable. Consequently we discuss various strategies whereby probiotics may be engineered to create designer probiotics. Such innovative approaches include; a receptor mimicry strategy to create probiotics that target specific pathogens and toxins, a patho-biotechnology approach using pathogen-derived genes to create more robust probiotic stains with increased host and processing-associated stress tolerance profiles and meta-biotechnology, whereby, functional metagenomics may be used to identify novel genes from diverse and vastly unexplored environments, such as the human gut, for use in biotechnology and medicine. PMID:19930635

Probiotics and gastrointestinal disease: successes, problems and future prospects.

PubMed

Culligan, Eamonn P; Hill, Colin; Sleator, Roy D

2009-11-23

Gastrointestinal disease is a major cause of morbidity and mortality worldwide each year. Treatment of chronic inflammatory gastrointestinal conditions such as ulcerative colitis and Crohn's disease is difficult due to the ambiguity surrounding their precise aetiology. Infectious gastrointestinal diseases, such as various types of diarrheal disease are also becoming increasingly difficult to treat due to the increasing dissemination of antibiotic resistance among microorganisms and the emergence of the so-called 'superbugs'. Taking into consideration these problems, the need for novel therapeutics is essential. Although described for over a century probiotics have only been extensively researched in recent years. Their use in the treatment and prevention of disease, particularly gastrointestinal disease, has yielded many successful results, some of which we outline in this review. Although promising, many probiotics are hindered by inherent physiological and technological weaknesses and often the most clinically promising strains are unusable. Consequently we discuss various strategies whereby probiotics may be engineered to create designer probiotics. Such innovative approaches include; a receptor mimicry strategy to create probiotics that target specific pathogens and toxins, a patho-biotechnology approach using pathogen-derived genes to create more robust probiotic stains with increased host and processing-associated stress tolerance profiles and meta-biotechnology, whereby, functional metagenomics may be used to identify novel genes from diverse and vastly unexplored environments, such as the human gut, for use in biotechnology and medicine.

Hunting for the function of orphan GPCRs – beyond the search for the endogenous ligand

PubMed Central

Ahmad, Raise; Wojciech, Stefanie; Jockers, Ralf

2015-01-01

Seven transmembrane-spanning proteins (7TM), also called GPCRs, are among the most versatile and evolutionary successful protein families. Out of the 400 non-odourant members identified in the human genome, approximately 100 remain orphans that have not been matched with an endogenous ligand. Apart from the classical deorphanization strategies, several alternative strategies provided recent new insights into the function of these proteins, which hold promise for high therapeutic potential. These alternative strategies consist of the phenotypical characterization of organisms silenced or overexpressing orphan 7TM proteins, the search for constitutive receptor activity and formation of protein complexes including 7TM proteins as well as the development of synthetic, surrogate ligands. Taken together, a variety of ligand-independent functions can be attributed to orphan 7TM proteins that range from constitutive activity to complex formation with other proteins and include ‘true’ orphans for which no ligand exist and ‘conditional’ orphans that behave like orphans in the absence of ligand and as non-orphans in the presence of ligand. PMID:25231237

[New perspectives on molecular and genic therapies in Down syndrome].

PubMed

Delabar, Jean Maurice

2010-04-01

Trisomy 21 was first described as a syndrome in the middle of the nineteenth century and associated to a chromosomic anomaly one hundred years later: the most salient feature of this syndrome is a mental retardation of variable intensity. Molecular mapping and DNA sequencing have allowed identifying the gene content of chromosome 21. Molecular quantitative analyses indicated that trisomy is inducing an overexpression for a large part of the triplicated genes and deregulates also pathways involving non HSA21 genes. Together with the physiological description of murine models overexpressing orthologous genes, these data have allowed to elaborate hypotheses on the cause of cognitive impairment. From these hypotheses and using murine models it is now possible to assess the efficiency of various therapeutic strategies. This paper reviews these new perspectives starting from the strategies targeting the level of HSA21 RNAs or HSA21 proteins; then it describes methods targeting activities either of proteins involved in cell cycle pathways or of proteins controlling the synaptic plasticity. It is promising that strategies targeting specific genes or specific pathways are already giving positive results.

Selective BET bromodomain inhibition as an antifungal therapeutic strategy

PubMed Central

Mietton, Flore; Ferri, Elena; Champleboux, Morgane; Zala, Ninon; Maubon, Danièle; Zhou, Yingsheng; Harbut, Mike; Spittler, Didier; Garnaud, Cécile; Courçon, Marie; Chauvel, Murielle; d'Enfert, Christophe; Kashemirov, Boris A.; Hull, Mitchell; Cornet, Muriel; McKenna, Charles E.; Govin, Jérôme; Petosa, Carlo

2017-01-01

Invasive fungal infections cause significant morbidity and mortality among immunocompromised individuals, posing an urgent need for new antifungal therapeutic strategies. Here we investigate a chromatin-interacting module, the bromodomain (BD) from the BET family of proteins, as a potential antifungal target in Candida albicans, a major human fungal pathogen. We show that the BET protein Bdf1 is essential in C. albicans and that mutations inactivating its two BDs result in a loss of viability in vitro and decreased virulence in mice. We report small-molecule compounds that inhibit C. albicans Bdf1 with high selectivity over human BDs. Crystal structures of the Bdf1 BDs reveal binding modes for these inhibitors that are sterically incompatible with the human BET-binding pockets. Furthermore, we report a dibenzothiazepinone compound that phenocopies the effects of a Bdf1 BD-inactivating mutation on C. albicans viability. These findings establish BET inhibition as a promising antifungal therapeutic strategy and identify Bdf1 as an antifungal drug target that can be selectively inhibited without antagonizing human BET function. PMID:28516956

Fruit and vegetable environment, policy, and pricing workshop: introduction to the conference proceedings.

PubMed

Seymour, Jennifer D; Fenley, Mary Ann; Yaroch, Amy Lazarus; Khan, Laura Kettel; Serdula, Mary

2004-09-01

Americans' consumption of fruits and vegetables has increased slightly over the last 10 years, but most people still do not meet the Dietary Guidelines recommendation to consume 5 to 9 servings per day. New and innovative strategies are needed if we are to significantly increase the mean population intake of fruits and vegetables. To help formulate such strategies as well as to evaluate evidence and identify research gaps, the American Cancer Society and the Centers for Disease Control and Prevention convened the Fruit and Vegetable Environment, Policy, and Pricing Workshop, which brought together experts in how environmental change, policy, and pricing affect fruit and vegetable consumption. The papers in this supplement consist of a review of environmental interventions to improve nutrition and papers covering pricing and consumer value and how fruit and vegetable consumption can be promoted at worksites, restaurants, grocery stores and other community settings, and schools. Conclusions from the workshop were that existing intervention strategies need to be evaluated, promising example programs need to be disseminated, and new innovative interventions and programs need to be created and evaluated.

Volatile decision dynamics: experiments, stochastic description, intermittency control and traffic optimization

NASA Astrophysics Data System (ADS)

Helbing, Dirk; Schönhof, Martin; Kern, Daniel

2002-06-01

The coordinated and efficient distribution of limited resources by individual decisions is a fundamental, unsolved problem. When individuals compete for road capacities, time, space, money, goods, etc, they normally make decisions based on aggregate rather than complete information, such as TV news or stock market indices. In related experiments, we have observed a volatile decision dynamics and far-from-optimal payoff distributions. We have also identified methods of information presentation that can considerably improve the overall performance of the system. In order to determine optimal strategies of decision guidance by means of user-specific recommendations, a stochastic behavioural description is developed. These strategies manage to increase the adaptibility to changing conditions and to reduce the deviation from the time-dependent user equilibrium, thereby enhancing the average and individual payoffs. Hence, our guidance strategies can increase the performance of all users by reducing overreaction and stabilizing the decision dynamics. These results are highly significant for predicting decision behaviour, for reaching optimal behavioural distributions by decision support systems and for information service providers. One of the promising fields of application is traffic optimization.

Pre-clinical therapeutic development of a series of metalloporphyrins for Parkinson's disease

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

Liang, Li-Ping

Reactive oxygen species are a well-defined therapeutic target for Parkinson's disease (PD) and pharmacological agents that catalytically scavenge reactive species are promising neuroprotective strategies for treatment. Metalloporphyrins are synthetic catalytic antioxidants that mimic the body's own antioxidant enzymes i.e. superoxide dismutases and catalase. The goal of this study was to determine if newly designed metalloporphyrins have enhanced pharmacodynamics including oral bioavailability, longer plasma elimination half-lives, penetrate the blood brain barrier, and show promise for PD treatment. Three metalloporphyrins (AEOL 11216, AEOL 11203 and AEOL 11114) were identified in this study as potential candidates for further pre-clinical development. Each of thesemore » compounds demonstrated blood brain barrier permeability by the i.p. route and two of three compounds (AEOL 11203 and AEOL 11114) were orally bioavailable. All of these compounds protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, including dopamine depletion in the striatum, dopaminergic neuronal loss in the substantial nigra, and increased oxidative/nitrative stress indices (glutathione disulfide and 3-nitrotyrosine) in the ventral midbrain of the mice without inhibiting MPTP metabolism. Daily therapeutic dosing of these metalloporphyrins were well tolerated without accumulation of brain manganese levels or behavioral alterations assessed by open field and rotarod tests. The study identified two orally active metalloporphyrins and one injectable metalloporphyrin as clinical candidates for further development in PD. - Highlights: • A series of metalloporphyrins were optimized in a mouse model of parkinsonism. • Two novel orally active, brain permeable antioxidant metalloporphyrins were identified. • The identified metalloporphyrins were well tolerated.« less

Tobacco control approaches and inequity--how far have we come and where are we going?

PubMed

Purcell, Kate R; O'Rourke, Kerryn; Rivis, Maya

2015-09-01

Despite Australia's success in reducing smoking rates, substantial inequities persist--with high smoking prevalence among disadvantaged groups. This article uses Fair Foundations: The VicHealth framework for health equity to identify promising strategies for promoting equity within tobacco control policies and programmes. A rapid review of the Australian and international literature was conducted in March 2014 using Pubmed, ISI web of Science and Scopus, Cochrane library and Google Scholar. A search of the grey literature was conducted to identify promising policy interventions. Population health surveys suggest that tobacco-related inequities in Victoria are beginning to decline. Data from the Victorian Smoking Survey shows that the inequity gap is narrowing, and in recent years, the prevalence of regular smoking declined fastest among disadvantaged smokers. Future approaches to accelerate reductions in tobacco-related inequities include: (i) continue proven population-based tobacco control policies--especially increasing the price of tobacco (while remaining cognisant of the increased economic burden for those smokers who do not quit), and continuing mass media campaigns; (ii) strengthening social policies to promote equity in early child development; educational experiences; quality of local environments; employment and working conditions; (iii) identifying and investing in targeted approaches to influence social norms and more effectively identify and support disadvantaged smokers to quit; (iv) within tobacco control programmes, give greatest priority to interventions focused on adult smokers (including pregnant women and their partners). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Optimization of vascular-targeting drugs in a computational model of tumor growth

NASA Astrophysics Data System (ADS)

Gevertz, Jana

2012-04-01

A biophysical tool is introduced that seeks to provide a theoretical basis for helping drug design teams assess the most promising drug targets and design optimal treatment strategies. The tool is grounded in a previously validated computational model of the feedback that occurs between a growing tumor and the evolving vasculature. In this paper, the model is particularly used to explore the therapeutic effectiveness of two drugs that target the tumor vasculature: angiogenesis inhibitors (AIs) and vascular disrupting agents (VDAs). Using sensitivity analyses, the impact of VDA dosing parameters is explored, as is the effects of administering a VDA with an AI. Further, a stochastic optimization scheme is utilized to identify an optimal dosing schedule for treatment with an AI and a chemotherapeutic. The treatment regimen identified can successfully halt simulated tumor growth, even after the cessation of therapy.

Sniffer dogs as part of a bimodal bionic research approach to develop a lung cancer screening†

PubMed Central

Boedeker, Enole; Friedel, Godehard; Walles, Thorsten

2012-01-01

Lung cancer (LC) continues to represent a heavy burden for health care systems worldwide. Epidemiological studies predict that its role will increase in the near future. While patient prognosis is strongly associated with tumour stage and early detection of disease, no screening test exists so far. It has been suggested that electronic sensor devices, commonly referred to as ‘electronic noses’, may be applicable to identify cancer-specific volatile organic compounds in the breath of patients and therefore may represent promising screening technologies. However, three decades of research did not bring forward a clinically applicable device. Here, we propose a new research approach by involving specially trained sniffer dogs into research strategies by making use of their ability to identify LC in the breath sample of patients. PMID:22345057

The demonstration of a theory-based approach to the design of localized patient safety interventions

PubMed Central

2013-01-01

Background There is evidence of unsafe care in healthcare systems globally. Interventions to implement recommended practice often have modest and variable effects. Ideally, selecting and adapting interventions according to local contexts should enhance effects. However, the means by which this can happen is seldom systematic, based on theory, or made transparent. This work aimed to demonstrate the applicability, feasibility, and acceptability of a theoretical domains framework implementation (TDFI) approach for co-designing patient safety interventions. Methods We worked with three hospitals to support the implementation of evidence-based guidance to reduce the risk of feeding into misplaced nasogastric feeding tubes. Our stepped process, informed by the TDF and key principles from implementation literature, entailed: involving stakeholders; identifying target behaviors; identifying local factors (barriers and levers) affecting behavior change using a TDF-based questionnaire; working with stakeholders to generate specific local strategies to address key barriers; and supporting stakeholders to implement strategies. Exit interviews and audit data collection were undertaken to assess the feasibility and acceptability of this approach. Results Following audit and discussion, implementation teams for each Trust identified the process of checking the positioning of nasogastric tubes prior to feeding as the key behavior to target. Questionnaire results indicated differences in key barriers between organizations. Focus groups generated innovative, generalizable, and adaptable strategies for overcoming barriers, such as awareness events, screensavers, equipment modifications, and interactive learning resources. Exit interviews identified themes relating to the benefits, challenges, and sustainability of this approach. Time trend audit data were collected for 301 patients over an 18-month period for one Trust, suggesting clinically significant improved use of pH and documentation of practice following the intervention. Conclusions The TDF is a feasible and acceptable framework to guide the implementation of patient safety interventions. The stepped TDFI approach engages healthcare professionals and facilitates contextualization in identifying the target behavior, eliciting local barriers, and selecting strategies to address those barriers. This approach may be of use to implementation teams and policy makers, although our promising findings confirm the need for a more rigorous evaluation; a balanced block evaluation is currently underway. PMID:24131864

Mindfulness practice: A promising approach to reducing the effects of clinician implicit bias on patients.

PubMed

Burgess, Diana J; Beach, Mary Catherine; Saha, Somnath

2017-02-01

Like the population at large, health care providers hold implicit racial and ethnic biases that may contribute to health care disparities. Little progress has been made in identifying and implementing effective strategies to address these normal but potentially harmful unconscious cognitive processes. We propose that meditation training designed to increase healthcare providers' mindfulness skills is a promising and potentially sustainable way to address this problem. Emerging evidence suggests that mindfulness practice can reduce the provider contribution to healthcare disparities through several mechanisms including: reducing the likelihood that implicit biases will be activated in the mind, increasing providers' awareness of and ability to control responses to implicit biases once activated, increasing self-compassion and compassion toward patients, and reducing internal sources of cognitive load (e.g., stress, burnout, and compassion fatigue). Mindfulness training may also have advantages over current approaches to addressing implicit bias because it focuses on the development of skills through practice, promotes a nonjudgmental approach, can circumvent resistance some providers feel when directly confronted with evidence of racism, and constitutes a holistic approach to promoting providers' well-being. We close with suggestions for how a mindfulness approach can be practically implemented and identify potential challenges and research gaps to be addressed. Published by Elsevier B.V.

Emerging Targets and Novel Approaches to Ebola Virus Prophylaxis and Treatment

PubMed Central

Choi, Jin Huk; Croyle, Maria A.

2013-01-01

Ebola is a highly virulent pathogen causing severe hemorrhagic fever with a high case fatality rate in humans and non-human primates (NHPs). Although safe and effective vaccines or other medicinal agents to block Ebola infection are currently unavailable, a significant effort has been put forth to identify several promising candidates for the treatment and prevention of Ebola hemorrhagic fever. Among these, recombinant-virus based vectors have been identified as potent vaccine candidates with some affording both pre- and post-exposure protection from the virus. Recently, Investigational New Drug (IND) applications have been approved by the United States (U.S.) Food and Drug Administration (FDA) and Phase I clinical trials initiated for two small molecule therapeutics, 1) anti-sense phosphorodiamidate morphino oligomers (PMOs: AVI-6002, AVI-6003), and 2) lipid-nanoparticle/small interfering RNA (LNP/siRNA: TKM-Ebola). These potential alternatives to vector-based vaccines require multiple doses to achieve therapeutic efficacy which is not ideal with regard to patient compliance and outbreak scenarios. These concerns have fueled a quest for even better vaccination and treatment strategies. Here, we summarize recent advances in vaccines or post-exposure therapeutics for prevention of Ebola hemorrhagic fever. The utility of novel pharmaceutical approaches to refine and overcome barriers associated with the most promising therapeutic platforms will also be discussed. PMID:23813435

Cation-exchanged zeolites for the selective oxidation of methane to methanol

DOE PAGES

Kulkarni, Ambarish R.; Zhao, Zhi-Jian; Siahrostami, Samira; ...

2017-10-19

Motivated by the increasing availability of cheap natural gas resources, considerable experimental and computational research efforts have focused on identifying selective catalysts for the direct conversion of methane to methanol. One promising class of catalysts are cation-exchanged zeolites, which have steadily increased in popularity over the past decade. Here, in this article, we first present a broad overview of this field from a conceptual perspective, and highlight the role of theory in developing a molecular-level understanding of the reaction. Next, by performing and analyzing a large database of density functional theory (DFT) calculations for a wide range of transition metalmore » cations, zeolite topologies and active site motifs, we present a unifying picture of the methane activation process in terms of active site stability, C–H bond activation and methanol extraction. Based on the trade-offs of active site stability and reactivity, we propose a framework for identifying new, promising active site motifs in these systems. Further, we show that the high methanol selectivity arises due to the strong binding nature of the C–H activation products. Lastly, using the atomistic and mechanistic insight obtained from these analyses, we summarize the key challenges and future strategies for improving the performance of cation-exchanged zeolites for this industrially relevant conversion.« less

Certificates of Confidentiality: Protecting Human Subject Research Data in Law and Practice

PubMed Central

Patel, Mayank J.; Williams, Brett A.; Austin, Jeffrey L.; Dame, Lauren A.

2014-01-01

Researchers often require and collect sensitive information about individuals to answer important scientific questions that impact individual health and well-being and the public health. Researchers recognize they have a duty to maintain the confidentiality of the data they collect and typically make promises, which are documented in the consent form. The legal interests of others, however, can threaten researchers’ promises of confidentiality, if they seek access to the data through subpoena. Certificates of Confidentiality (Certificates), authorized by federal statute, are an important tool for protecting individually identifiable sensitive research data from compelled disclosure. However, questions persist in the research community about the strength of Certificate protections, and the evidence on which to judge the strength is scant. In this article, we address those questions through a careful examination of the legislation and regulations concerning Certificates and the reported and unreported cases we have identified through our legal research and interviews with legal counsel about their experiences with Certificates. We also analyze other statutes that protect research data to compare them to the Certificate’s protections, and we review other legal strategies available for protecting research data. Based on our analysis, we conclude with recommendations for how to strengthen protection of sensitive research data. PMID:25392705

Cation-exchanged zeolites for the selective oxidation of methane to methanol

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

Kulkarni, Ambarish R.; Zhao, Zhi-Jian; Siahrostami, Samira

Motivated by the increasing availability of cheap natural gas resources, considerable experimental and computational research efforts have focused on identifying selective catalysts for the direct conversion of methane to methanol. One promising class of catalysts are cation-exchanged zeolites, which have steadily increased in popularity over the past decade. Here, in this article, we first present a broad overview of this field from a conceptual perspective, and highlight the role of theory in developing a molecular-level understanding of the reaction. Next, by performing and analyzing a large database of density functional theory (DFT) calculations for a wide range of transition metalmore » cations, zeolite topologies and active site motifs, we present a unifying picture of the methane activation process in terms of active site stability, C–H bond activation and methanol extraction. Based on the trade-offs of active site stability and reactivity, we propose a framework for identifying new, promising active site motifs in these systems. Further, we show that the high methanol selectivity arises due to the strong binding nature of the C–H activation products. Lastly, using the atomistic and mechanistic insight obtained from these analyses, we summarize the key challenges and future strategies for improving the performance of cation-exchanged zeolites for this industrially relevant conversion.« less

A type 2 diacylglycerol acyltransferase accelerates the triacylglycerol biosynthesis in heterokont oleaginous microalga Nannochloropsis oceanica.

PubMed

Li, Da-Wei; Cen, Shi-Ying; Liu, Yu-Hong; Balamurugan, Srinivasan; Zheng, Xin-Yan; Alimujiang, Adili; Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye

2016-07-10

Oleaginous microalgae have received a considerable attention as potential biofuel feedstock. However, lack of industry-suitable strain with lipid rich biomass limits its commercial applications. Targeted engineering of lipogenic pathways represents a promising strategy to enhance the efficacy of microalgal oil production. In this study, a type 2 diacylglycerol acyltransferase (DGAT), a rate-limiting enzyme in triacylglycerol (TAG) biosynthesis, was identified and overexpressed in heterokont oleaginous microalga Nannochloropsis oceanica for the first time. Overexpression of DGAT2 in Nannochloropsis increased the relative transcript abundance by 3.48-fold in engineered microalgae cells. TAG biosynthesis was subsequently accelerated by DGAT2 overexpression and neutral lipid content was significantly elevated by 69% in engineered microalgae. The fatty acid profile determined by GC-MS revealed that fatty acid composition was altered in engineered microalgae. Saturated fatty acids and polyunsaturated fatty acids were found to be increased whereas monounsaturated fatty acids content decreased. Furthermore, DGAT2 overexpression did not show negative impact on algal growth parameters. The present investigation showed that the identified DGAT2 would be a potential candidate for enhancing TAG biosynthesis and might facilitate the development of promising oleaginous strains with industrial potential. Copyright © 2016 Elsevier B.V. All rights reserved.

Recent Advances in Nanostructured Thermoelectric Half-Heusler Compounds

PubMed Central

Xie, Wenjie; Weidenkaff, Anke; Tang, Xinfeng; Zhang, Qingjie; Poon, Joseph; Tritt, Terry M.

2012-01-01

Half-Heusler (HH) alloys have attracted considerable interest as promising thermoelectric (TE) materials in the temperature range around 700 K and above, which is close to the temperature range of most industrial waste heat sources. The past few years have seen nanostructuing play an important role in significantly enhancing the TE performance of several HH alloys. In this article, we briefly review the recent progress and advances in these HH nanocomposites. We begin by presenting the structure of HH alloys and the different strategies that have been utilized for improving the TE properties of HH alloys. Next, we review the details of HH nanocomposites as obtained by different techniques. Finally, the review closes by highlighting several promising strategies for further research directions in these very promising TE materials. PMID:28348315

Evolvable Mars Campaign Long Duration Habitation Strategies: Architectural Approaches to Enable Human Exploration Missions

NASA Technical Reports Server (NTRS)

Simon, Matthew A.; Toups, Larry; Howe, A. Scott; Wald, Samuel I.

2015-01-01

The Evolvable Mars Campaign (EMC) is the current NASA Mars mission planning effort which seeks to establish sustainable, realistic strategies to enable crewed Mars missions in the mid-2030s timeframe. The primary outcome of the Evolvable Mars Campaign is not to produce "The Plan" for sending humans to Mars, but instead its intent is to inform the Human Exploration and Operations Mission Directorate near-term key decisions and investment priorities to prepare for those types of missions. The FY'15 EMC effort focused upon analysis of integrated mission architectures to identify technically appealing transportation strategies, logistics build-up strategies, and vehicle designs for reaching and exploring Mars moons and Mars surface. As part of the development of this campaign, long duration habitats are required which are capable of supporting crew with limited resupply and crew abort during the Mars transit, Mars moons, and Mars surface segments of EMC missions. In particular, the EMC design team sought to design a single, affordable habitation system whose manufactured units could be outfitted uniquely for each of these missions and reused for multiple crewed missions. This habitat system must provide all of the functionality to safely support 4 crew for long durations while meeting mass and volume constraints for each of the mission segments set by the chosen transportation architecture and propulsion technologies. This paper describes several proposed long-duration habitation strategies to enable the Evolvable Mars Campaign through improvements in mass, cost, and reusability, and presents results of analysis to compare the options and identify promising solutions. The concepts investigated include several monolithic concepts: monolithic clean sheet designs, and concepts which leverage the co-manifested payload capability of NASA's Space Launch System (SLS) to deliver habitable elements within the Universal Payload Adaptor between the SLS upper stage and the Orion/Service module on the top of the vehicle. Multiple modular habitat options for Mars surface and in-space missions are also considered with various functionality and volume splits between modules to find the best balance of reducing the single largest mass which must be delivered to a destination and reducing the number of separate elements which must be launched. Analysis results presented for each of these concepts in this paper include mass/volume/power sizing using parametric sizing tools, identification of unique operational constraints, and limited comments on the additional impacts of reusability/dormancy on system design. Finally, recommendations will be made for promising solutions which will be carried forward for consideration in the Evolvable Mars Campaign work.

Computer Simulation in Tomorrow's Schools.

ERIC Educational Resources Information Center

Foster, David

1984-01-01

Suggests use of simulation as an educational strategy has promise for the school of the future; discusses specific advantages of simulations over alternative educational methods, role of microcomputers in educational simulation, and past obstacles and future promise of microcomputer simulations; and presents a literature review on effectiveness of…

Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review.

PubMed

Pasin, Daniel; Cawley, Adam; Bidny, Sergei; Fu, Shanlin

2017-10-01

The proliferation of new psychoactive substances (NPS) in recent years has resulted in the development of numerous analytical methods for the detection and identification of known and unknown NPS derivatives. High-resolution mass spectrometry (HRMS) has been identified as the method of choice for broad screening of NPS in a wide range of analytical contexts because of its ability to measure accurate masses using data-independent acquisition (DIA) techniques. Additionally, it has shown promise for non-targeted screening strategies that have been developed in order to detect and identify novel analogues without the need for certified reference materials (CRMs) or comprehensive mass spectral libraries. This paper reviews the applications of HRMS for the analysis of NPS in forensic drug chemistry and analytical toxicology. It provides an overview of the sample preparation procedures in addition to data acquisition, instrumental analysis, and data processing techniques. Furthermore, it gives an overview of the current state of non-targeted screening strategies with discussion on future directions and perspectives of this technique. Graphical Abstract Missing the bullseye - a graphical respresentation of non-targeted screening. Image courtesy of Christian Alonzo.

Mindfulness as a strategy for coping with cue-elicited cravings for alcohol: an experimental examination.

PubMed

Murphy, Cara M; MacKillop, James

2014-04-01

Mindfulness has been identified as a promising strategy for managing cravings for alcohol and other drugs, but little controlled experimental research has directly studied whether this approach is effective. The current study systematically examined the effects of an acute mindfulness manipulation on craving for alcohol during prolonged exposure to alcohol cues. Heavy drinkers (N = 84, 50% male) underwent a prolonged alcohol cue exposure paradigm in a simulated bar environment and received either a mindfulness-based strategy, a distraction (DST)-based strategy (active control), or no strategy (passive control) to cope with alcohol cravings and discomfort associated with craving. No baseline differences were present between conditions. Manipulation checks revealed that participants in the 2 active conditions reported using the recommended strategies. Across groups, the initial exposure to alcohol cues was associated with significant increases in craving, urge distress, and heart rate. Mixed analyses of variance on these indices following the experimental manipulation revealed significant differences based on condition over the course of the bar laboratory protocol. The DST strategy was significantly more effective at acutely reducing craving and urge distress than the other 2 conditions, which did not significantly differ from each other. Contrary to our prediction, these findings suggest that an acute DSTstrategy is beneficial for coping with alcohol cravings. The potential importance of protracted mindfulness training to detect significant effects on in vivo craving, additional implications, and methodological considerations are discussed. Copyright © 2013 by the Research Society on Alcoholism.

Current available strategies to mitigate greenhouse gas emissions in livestock systems: an animal welfare perspective.

PubMed

Llonch, P; Haskell, M J; Dewhurst, R J; Turner, S P

2017-02-01

Livestock production is a major contributor to greenhouse gas (GHG) emissions, so will play a significant role in the mitigation effort. Recent literature highlights different strategies to mitigate GHG emissions in the livestock sector. Animal welfare is a criterion of sustainability and any strategy designed to reduce the carbon footprint of livestock production should consider animal welfare amongst other sustainability metrics. We discuss and tabulate the likely relationships and trade-offs between the GHG mitigation potential of mitigation strategies and their welfare consequences, focusing on ruminant species and on cattle in particular. The major livestock GHG mitigation strategies were classified according to their mitigation approach as reducing total emissions (inhibiting methane production in the rumen), or reducing emissions intensity (Ei; reducing CH4 per output unit without directly targeting methanogenesis). Strategies classified as antimethanogenic included chemical inhibitors, electron acceptors (i.e. nitrates), ionophores (i.e. Monensin) and dietary lipids. Increasing diet digestibility, intensive housing, improving health and welfare, increasing reproductive efficiency and breeding for higher productivity were categorized as strategies that reduce Ei. Strategies that increase productivity are very promising ways to reduce the livestock carbon footprint, though in intensive systems this is likely to be achieved at the cost of welfare. Other strategies can effectively reduce GHG emissions whilst simultaneously improving animal welfare (e.g. feed supplementation or improving health). These win-win strategies should be strongly supported as they address both environmental and ethical sustainability. In order to identify the most cost-effective measures for improving environmental sustainability of livestock production, the consequences of current and future strategies for animal welfare must be scrutinized and contrasted against their effectiveness in mitigating climate change.

Marine Microbiological Enzymes: Studies with Multiple Strategies and Prospects.

PubMed

Wang, Yan; Song, Qinghao; Zhang, Xiao-Hua

2016-09-22

Marine microorganisms produce a series of promising enzymes that have been widely used or are potentially valuable for our daily life. Both classic and newly developed biochemistry technologies have been broadly used to study marine and terrestrial microbiological enzymes. In this brief review, we provide a research update and prospects regarding regulatory mechanisms and related strategies of acyl-homoserine lactones (AHL) lactonase, which is an important but largely unexplored enzyme. We also detail the status and catalytic mechanism of the main types of polysaccharide-degrading enzymes that broadly exist among marine microorganisms but have been poorly explored. In order to facilitate understanding, the regulatory and synthetic biology strategies of terrestrial microorganisms are also mentioned in comparison. We anticipate that this review will provide an outline of multiple strategies for promising marine microbial enzymes and open new avenues for the exploration, engineering and application of various enzymes.

Reaching Success through Involvement--Implementation Strategy for Creating and Maintaining Effective Schools.

ERIC Educational Resources Information Center

Furtwengler, Willis J.

The educational change strategy termed "reaching success through involvement" (RSI) has yielded promising results in creating school effectiveness. This paper analyzes the theoretical bases and practical applications of RSI strategy among 14 schools over an 8-year period. RSI theory assumes that educational organizations are dynamic social systems…

Educating Homeless Students: Promising Practices.

ERIC Educational Resources Information Center

Stronge, James H., Ed.; Reed-Victor, Evelyn, Ed.

This book is for educators who serve homeless students or students temporarily sharing houses with other families. It describes many promising strategies for working with these students. The chapters are: (1) "Educating Homeless Children and Youth: An Introduction" (James H. Stronge); (2) "Meeting the Developmental and Educational Needs of…

Exploring Alcohol Policy Approaches to Prevent Sexual Violence Perpetration

PubMed Central

Lippy, Caroline; DeGue, Sarah

2018-01-01

Sexual violence continues to be a significant public health problem worldwide with serious consequences for individuals and communities. The implementation of prevention strategies that address risk and protective factors for sexual violence at the community level are important components of a comprehensive approach, but few such strategies have been identified or evaluated. The current review explores one potential opportunity for preventing sexual violence perpetration at the community level: alcohol policy. Alcohol policy has the potential to impact sexual violence perpetration through the direct effects of excessive alcohol consumption on behavior or through the impact of alcohol and alcohol outlets on social organization within communities. Policies affecting alcohol pricing, sale time, outlet density, drinking environment, marketing, and college environment are reviewed to identify existing evidence of impact on rates of sexual violence or related outcomes, including risk factors and related health behaviors. Several policy areas with initial evidence of an association with sexual violence outcomes were identified, including policies affecting alcohol pricing, alcohol outlet density, barroom management, sexist content in alcohol marketing, and policies banning alcohol on campus and in substance-free dorms. We identify other policy areas with evidence of an impact on related outcomes and risk factors that may also hold potential as a preventative approach for sexual violence perpetration. Evidence from the current review suggests that alcohol policy may represent one promising avenue for the prevention of sexual violence perpetration at the community level, but additional research is needed to directly examine effects on sexual violence outcomes. PMID:25403447

Exploring Alcohol Policy Approaches to Prevent Sexual Violence Perpetration.

PubMed

Lippy, Caroline; DeGue, Sarah

2016-01-01

Sexual violence continues to be a significant public health problem worldwide with serious consequences for individuals and communities. The implementation of prevention strategies that address risk and protective factors for sexual violence at the community level are important components of a comprehensive approach, but few such strategies have been identified or evaluated. The current review explores one potential opportunity for preventing sexual violence perpetration at the community level: alcohol policy. Alcohol policy has the potential to impact sexual violence perpetration through the direct effects of excessive alcohol consumption on behavior or through the impact of alcohol and alcohol outlets on social organization within communities. Policies affecting alcohol pricing, sale time, outlet density, drinking environment, marketing, and college environment are reviewed to identify existing evidence of impact on rates of sexual violence or related outcomes, including risk factors and related health behaviors. Several policy areas with initial evidence of an association with sexual violence outcomes were identified, including policies affecting alcohol pricing, alcohol outlet density, barroom management, sexist content in alcohol marketing, and policies banning alcohol on campus and in substance-free dorms. We identify other policy areas with evidence of an impact on related outcomes and risk factors that may also hold potential as a preventative approach for sexual violence perpetration. Evidence from the current review suggests that alcohol policy may represent one promising avenue for the prevention of sexual violence perpetration at the community level, but additional research is needed to directly examine effects on sexual violence outcomes. © The Author(s) 2014.

Opportunities to protect instream flows and wetland uses of water in Florida

USGS Publications Warehouse

Burkardt, Nina

1990-01-01

This document combines the efforts of several individuals, agencies, and organizations toward a common objective: the identification, description, and preliminary evaluation of promising opportunities for protecting instream uses of water under existing laws in Florida. this report is intended for the use of State and Federal planning and management personnel who need an overview of potential opportunities for preserving instream flows. It is not intended to replace or challenge the advice of agency counsel, nor is it written to provide legal advice. Instead, it is designed as a guide for the person trying to find his way among sometimes bewildering State statutes and administrative practices. This report is not, and should not be taken as, official policy or prediction of future actions by any agency. It is simply a summary of some potential opportunities for protecting instream uses. Toward these objectives, the U.S. Fish and Wildlife Service, through its Water Resource Analysis Project, contracted in 1977 with R. Dewsnup and D. Jensen to identify available strategies under State and Federal laws, interstate compacts, and water quality laws. A second firm, Enviro Control, Inc., was contracted to evaluate the most promising strategies. The resulting documents reported instream flow strategies for 11 States. These reports have been revised, updated, and combined in a number of new monographs, and the Service has added more States to this service over the years. The discussion of instream flow programs and opportunities for each State is written so that each report can be read independently, with minimal cross-referencing from one State report to another. The opportunities for Florida are summarized in the table.

Impact of telemonitoring approaches on integrated HIV and TB diagnosis and treatment interventions in sub-Saharan Africa: a scoping review.

PubMed

Yah, Clarence S; Tambo, Ernest; Khayeka-Wandabwa, Christopher; Ngogang, Jeanne Y

2017-01-01

Background: This paper explores telemonitoring/mhealth approaches as a promising real time and contextual strategy in overhauling HIV and TB interventions quality access and uptake, retention,adherence and coverage impact in endemic and prone-epidemic prevention and control in sub-Sahara Africa. Methods: The scoping review method was applied in acknowledged journals indexing platforms including Medline, Embase, Global Health, PubMed, MeSH PsycInfo, Scopus and Google Scholar to identify relevant articles pertaining to telemonitoring as a proxy surrogate method in reinforcing sustainability of HIV/TB prevention/treatment interventions in sub-Saharan Africa. Full papers were assessed and those selected that fosters evidence on telemonitoring/mhealth diagnosis, treatment approaches and strategies in HIV and TB prevention and control were synthesized and analyzed. Results: We found telemonitoring/mhealth approach as a more efficient and sustained proxy in HIV and TB risk reduction strategies for early diagnosis and prompt quality clinical outcomes. It can significantly contribute to decreasing health systems/patients cost, long waiting time in clinics, hospital visits, travels and time off/on from work. Improved integrated HIV and TB telemonitoring systems sustainability hold great promise in health systems strengthening including patient centered early diagnosis and care delivery systems, uptake and retention to medications/services and improving patients' survival and quality of life. Conclusion: Telemonitoring/mhealth (electronic phone text/video/materials messaging)acceptability, access and uptake are crucial in monitoring and improving uptake, retention,adherence and coverage in both local and national integrated HIV and TB programs and interventions. Moreover, telemonitoring is crucial in patient-providers-health professional partnership, real-time quality care and service delivery, antiretroviral and anti-tuberculous drugs improvement, susceptibility monitoring and prescription choice, reinforcing cost effective HIV and TB integrated therapy model and survival rate.

Dentists United to Extinguish Tobacco (DUET): a study protocol for a cluster randomized, controlled trial for enhancing implementation of clinical practice guidelines for treating tobacco dependence in dental care settings.

PubMed

Ostroff, Jamie S; Li, Yuelin; Shelley, Donna R

2014-02-21

Although dental care settings provide an exceptional opportunity to reach smokers and provide brief cessation advice and treatment to reduce oral and other tobacco-related health conditions, dental care providers demonstrate limited adherence to evidence-based guidelines for treatment of tobacco use and dependence. Guided by a multi-level, conceptual framework that emphasizes changes in provider beliefs and organizational characteristics as drivers of improvement in tobacco treatment delivery, the current protocol will use a cluster, randomized design and multiple data sources (patient exit interviews, provider surveys, site observations, chart audits, and semi-structured provider interviews) to study the process of implementing clinical practice guidelines for treating tobacco dependence in 18 public dental care clinics in New York City. The specific aims of this comparative-effectiveness research trial are to: compare the effectiveness of three promising strategies for implementation of tobacco use treatment guidelines-staff training and current best practices (CBP), CBP + provider performance feedback (PF), and CBP + PF + provider reimbursement for delivery of tobacco cessation treatment (pay-for-performance, or P4P); examine potential theory-driven mechanisms hypothesized to explain the comparative effectiveness of three strategies for implementation; and identify baseline organizational factors that influence the implementation of evidence-based tobacco use treatment practices in dental clinics. The primary outcome is change in providers' tobacco treatment practices and the secondary outcomes are cost per quit, use of tobacco cessation treatments, quit attempts, and smoking abstinence. We hypothesize that the value of these promising implementation strategies is additive and that incorporating all three strategies (CBP, PF, and P4P) will be superior to CBP alone and CBP + PF in improving delivery of cessation assistance to smokers. The findings will improve knowledge pertinent to the implementation, dissemination, and sustained utilization of evidence-based tobacco use treatment in dental practices. NCT01615237.

LaAlO3:Mn4+ as Near-Infrared Emitting Persistent Luminescence Phosphor for Medical Imaging: A Charge Compensation Study

PubMed Central

De Clercq, Olivier Q.; Korthout, Katleen

2017-01-01

Mn4+-activated phosphors are emerging as a novel class of deep red/near-infrared emitting persistent luminescence materials for medical imaging as a promising alternative to Cr3+-doped nanomaterials. Currently, it remains a challenge to improve the afterglow and photoluminescence properties of these phosphors through a traditional high-temperature solid-state reaction method in air. Herein we propose a charge compensation strategy for enhancing the photoluminescence and afterglow performance of Mn4+-activated LaAlO3 phosphors. LaAlO3:Mn4+ (LAO:Mn4+) was synthesized by high-temperature solid-state reaction in air. The charge compensation strategies for LaAlO3:Mn4+ phosphors were systematically discussed. Interestingly, Cl−/Na+/Ca2+/Sr2+/Ba2+/Ge4+ co-dopants were all found to be beneficial for enhancing LaAlO3:Mn4+ luminescence and afterglow intensity. This strategy shows great promise and opens up new avenues for the exploration of more promising near-infrared emitting long persistent phosphors for medical imaging. PMID:29231901

Management of Myelofibrosis-Related Cytopenias.

PubMed

Bose, Prithviraj; Verstovsek, Srdan

2018-05-23

Cytopenias, particularly anemia, are frequently encountered in patients with myelofibrosis. Management of cytopenias in myelofibrosis can be very challenging because current therapeutic interventions are only of modest efficacy and ruxolitinib, the only approved drug for myelofibrosis, is myelosuppressive. Yet, dose optimization of ruxolitinib is important for its survival benefit in patients with advanced disease. We sought to summarize the data on treatments for cytopenias available at present and review promising agents in development and emerging strategies. The activin receptor ligand traps hold considerable promise for the treatment of anemia and could represent an attractive combination strategy with ruxolitinib. Low-dose thalidomide, which could offset both anemia and thrombocytopenia caused by ruxolitinib, represents another potential partner for ruxolitinib. The anti-fibrotic agent PRM-151 produced sustained improvements in cytopenias in some patients, and further data on this drug are eagerly awaited. Finally, several preclinical leads with translational potential are worthy of clinical investigation as strategies to halt/reverse bone marrow fibrosis and thereby improve cytopenias. Cytopenias remain a significant hurdle in myelofibrosis management, but several novel investigational agents hold considerable promise for the future.

Field testing a questionnaire assessing parental psychosocial factors related to consumption of calcium-rich foods by Hispanic, Asian, and Non-Hispanic white young adolescent children.

PubMed

Vyduna, Jennifer L; Boushey, Carol J; Bruhn, Christine M; Reicks, Marla; Auld, Garry W; Cluskey, Mary; Edlefsen, Miriam; Misner, Scottie; Olson, Beth; Schram, Jessica; Zaghloul, Sahar

2016-01-01

Intervention strategies to increase calcium intake of parents and young adolescent children could be improved by identifying psychosocial factors influencing intake. The objective was to develop a tool to assess factors related to calcium intake among parents and Hispanic, Asian, and non-Hispanic white young adolescent children (10-13 years) meeting acceptable standards for psychometric properties. A parent questionnaire was constructed from interviews conducted to identify factors. Parents (n = 166) in the United States completed the questionnaire, with seventy-one completing it twice. Two constructs (Attitudes/Preferences and Social/Environmental) were identified and described by eighteen subscales with Cronbach's alpha levels from .50 to .79. Test-retest coefficients ranged from .68 to .85 (p < .001). Several subscales were statistically significantly associated with parent characteristics consistent with theory and published literature. This tool shows promise as a valid and reliable measure of factors associated with calcium-rich food intake among parents and young adolescent children.

Identifying WIMP dark matter from particle and astroparticle data

NASA Astrophysics Data System (ADS)

Bertone, Gianfranco; Bozorgnia, Nassim; Kim, Jong Soo; Liem, Sebastian; McCabe, Christopher; Otten, Sydney; Ruiz de Austri, Roberto

2018-03-01

One of the most promising strategies to identify the nature of dark matter consists in the search for new particles at accelerators and with so-called direct detection experiments. Working within the framework of simplified models, and making use of machine learning tools to speed up statistical inference, we address the question of what we can learn about dark matter from a detection at the LHC and a forthcoming direct detection experiment. We show that with a combination of accelerator and direct detection data, it is possible to identify newly discovered particles as dark matter, by reconstructing their relic density assuming they are weakly interacting massive particles (WIMPs) thermally produced in the early Universe, and demonstrating that it is consistent with the measured dark matter abundance. An inconsistency between these two quantities would instead point either towards additional physics in the dark sector, or towards a non-standard cosmology, with a thermal history substantially different from that of the standard cosmological model.

The Promise and Potential Perils of Big Data for Advancing Symptom Management Research in Populations at Risk for Health Disparities.

PubMed

Bakken, Suzanne; Reame, Nancy

2016-01-01

Symptom management research is a core area of nursing science and one of the priorities for the National Institute of Nursing Research, which specifically focuses on understanding the biological and behavioral aspects of symptoms such as pain and fatigue, with the goal of developing new knowledge and new strategies for improving patient health and quality of life. The types and volume of data related to the symptom experience, symptom management strategies, and outcomes are increasingly accessible for research. Traditional data streams are now complemented by consumer-generated (i.e., quantified self) and "omic" data streams. Thus, the data available for symptom science can be considered big data. The purposes of this chapter are to (a) briefly summarize the current drivers for the use of big data in research; (b) describe the promise of big data and associated data science methods for advancing symptom management research; (c) explicate the potential perils of big data and data science from the perspective of the ethical principles of autonomy, beneficence, and justice; and (d) illustrate strategies for balancing the promise and the perils of big data through a case study of a community at high risk for health disparities. Big data and associated data science methods offer the promise of multidimensional data sources and new methods to address significant research gaps in symptom management. If nurse scientists wish to apply big data and data science methods to advance symptom management research and promote health equity, they must carefully consider both the promise and perils.

Community Schools as an Effective Strategy for Reform. Research Brief

ERIC Educational Resources Information Center

Daniel, Julia; Snyder, Jon David

2016-01-01

Research literature finds that community school models offering various agreed-upon features provide an excellent social return on investment and significant promise for providing opportunities for learning and promoting well-being in students and communities. Community schools show significant promise for addressing barriers to learning and…

Educating Emotionally Disturbed Children--Promising Practices. Journal within a Journal.

ERIC Educational Resources Information Center

Michael, Robert, Ed.

1987-01-01

Seven articles by educators with a variety of perspectives examine promising educational practices for use with children having emotional disturbances. Lee Bell offers strategies for using group activities in "All Together Now: Group Techniques for Teaching Students with Emotional Disturbances." Lyn Sarda and Rik Flynn discuss benefits…

Rapid Identification of Chemoresistance Mechanisms Using Yeast DNA Mismatch Repair Mutants

PubMed Central

Ojini, Irene; Gammie, Alison

2015-01-01

Resistance to cancer therapy is a major obstacle in the long-term treatment of cancer. A greater understanding of drug resistance mechanisms will ultimately lead to the development of effective therapeutic strategies to prevent resistance from occurring. Here, we exploit the mutator phenotype of mismatch repair defective yeast cells combined with whole genome sequencing to identify drug resistance mutations in key pathways involved in the development of chemoresistance. The utility of this approach was demonstrated via the identification of the known CAN1 and TOP1 resistance targets for two compounds, canavanine and camptothecin, respectively. We have also experimentally validated the plasma membrane transporter HNM1 as the primary drug resistance target of mechlorethamine. Furthermore, the sequencing of mitoxantrone-resistant strains identified inactivating mutations within IPT1, a gene encoding inositolphosphotransferase, an enzyme involved in sphingolipid biosynthesis. In the case of bactobolin, a promising anticancer drug, the endocytosis pathway was identified as the drug resistance target responsible for conferring resistance. Finally, we show that that rapamycin, an mTOR inhibitor previously shown to alter the fitness of the ipt1 mutant, can effectively prevent the formation of mitoxantrone resistance. The rapid and robust nature of these techniques, using Saccharomyces cerevisiae as a model organism, should accelerate the identification of drug resistance targets and guide the development of novel therapeutic combination strategies to prevent the development of chemoresistance in various cancers. PMID:26199284

Characterizing the syphilis epidemic among men who have sex with men in Lima, Peru to identify new treatment and control strategies

PubMed Central

2013-01-01

Background Syphilis is an important sexually transmitted infection (STI) with serious public health consequences. Among men who have sex with men (MSM) in Lima, the prevalence and incidence are extraordinarily high. Current syndromic approaches, however, fail to identify asymptomatic cases, and in settings where large proportions of individuals test positive again after treatment, it is frequently difficult to distinguish treatment failure from re-infection. Thus, new approaches are needed to improve treatment strategies and public health control efforts. Methods/Design Study participants will undergo baseline testing for syphilis infection along with a behavioral survey covering demographics, sexual behavior, drug and alcohol abuse and health-care seeking behavior. The cohort will be followed for 18 months at three-month intervals. Blood and earlobe scrapings will also be collected for T. pallidum DNA testing, to create molecular markers for subtyping. We will also perform cytokine testing on collected samples in order to create host immunologic profiles associated with recurrence, re-infection, treatment failure and success. Discussion Advances in social epidemiology, molecular typing and characterization of host immune responses will offer promise in developing new understandings of syphilis management. We will share our findings with the Peruvian Ministry of Health and other public health organizations, to identify new approaches of case detection and successful treatment. PMID:24016185

Feasibility study for early removal of HEU from CPP-651-Phase II

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

Smith, C.V.; Henry, R.; Milligan, C.

1997-09-01

A two-phase feasibility study was initiated in late 1996 to identify a way to expedite the removal of SNM from the CPP-651 vault. The first phase of this study provided preliminary information that appeared promising, but needed additional detailed planning and evaluate to validate the concepts and conclusions. The focus of Phase 2 was to provide the validation via resource-loaded schedules and more detailed cost estimates. Section 1 describes the purpose and objectives of the Phase 2 tasks and the programmatic drivers that influence related CPP-651 high-enriched uranium (HEU) management issues. Section 2 identifies the evaluation criteria and methodology andmore » the transfer issues and barriers preventing shipment. Section 3 provides site-specific background information for the CPP-651 facility and the Idaho National Engineering and Environmental Laboratory (INEEL) and describes the development of the basic material removal schedule, the proposed base case plan for removal of SNM, and the proposed HEU material management/shipping issues and strategies. Section 4 identifies the proposed options for accelerated removal of SNM and how they were evaluated via detailed scheduling, resource histograms, and cost analysis. Section 5 summarizes principal tasks for implementing this plan and other related HEU CPP-651 management issues that require continued planning efforts to assure successful implementation of this proposed early removal strategy.« less

Considerations in the Design of Clinical Trials for Cognitive Aging

PubMed Central

Brinton, Roberta Diaz; Katz, Russell; Petersen, Ronald C.; Negash, Selam; Mungas, Dan; Aisen, Paul S.

2012-01-01

What will it take to develop interventions for the treatment of age-related cognitive decline? Session V of the Summit provided perspectives on the design of clinical trials to evaluate promising but unproven interventions, and some of the steps needed to accelerate the discovery and evaluation of promising treatments. It considered strategies to further characterize the biological and cognitive changes associated with normal aging and their translation into the development of new treatments. It provided regulatory, scientific, and clinical perspectives about neurocognitive aging treatments, their potential benefits and risks, and the strategies and endpoints needed to evaluate them in the most rapid, rigorous, and clinically meaningful way. It considered lessons learned from the study of Alzheimer's disease, the promising roles of biomarkers in neurocognitive aging research, and ways to help galvanize the scientific study and treatment of neurocognitive aging. PMID:22573913

Considerations in the design of clinical trials for cognitive aging.

PubMed

Reiman, Eric M; Brinton, Roberta Diaz; Katz, Russell; Petersen, Ronald C; Negash, Selam; Mungas, Dan; Aisen, Paul S

2012-06-01

What will it take to develop interventions for the treatment of age-related cognitive decline? Session V of the Summit provided perspectives on the design of clinical trials to evaluate promising but unproven interventions, and some of the steps needed to accelerate the discovery and evaluation of promising treatments. It considered strategies to further characterize the biological and cognitive changes associated with normal aging and their translation into the development of new treatments. It provided regulatory, scientific, and clinical perspectives about neurocognitive aging treatments, their potential benefits and risks, and the strategies and endpoints needed to evaluate them in the most rapid, rigorous, and clinically meaningful way. It considered lessons learned from the study of Alzheimer's disease, the promising roles of biomarkers in neurocognitive aging research, and ways to help galvanize the scientific study and treatment of neurocognitive aging.

A randomised controlled trial of an active telephone-based recruitment strategy to increase childcare-service staff attendance at a physical activity and nutrition training workshop.

PubMed

Yoong, Sze Lin; Wolfenden, Luke; Finch, Meghan; Williams, Amanda; Dodds, Pennie; Gillham, Karen; Wyse, Rebecca

2013-12-01

Centre-based childcare services represent a promising setting to target the prevention of excessive weight gain in preschool-aged children. Staff training is a key component of multi-strategy interventions to improve implementation of effective physical activity and nutrition promoting practices for obesity prevention in childcare services. This randomised controlled trial aimed to examine whether an active telephone-based strategy to invite childcare-service staff to attend a training workshop was effective in increasing the proportion of services with staff attending training, compared with a passive strategy. Services were randomised to an active telephone-based or a passive-recruitment strategy. Those in the active arm received an email invitation and one to three follow-up phone calls, whereas services in the passive arm were informed of the availability of training only via newsletters. The proportion of services with staff attending the training workshop was compared between the two arms. One hundred and twenty-eight services were included in this study. A significantly larger proportion (52%) of services in the active arm compared with those in the passive-strategy arm (3.1%) attended training (d.f.=1, χ2=34.3; P<0.001). An active, telephone-based recruitment strategy significantly increased the proportion of childcare services with staff attending training. Further strategies to improve staff attendance at training need to be identified and implemented. SO WHAT?: Active-recruitment strategies including follow-up telephone calls should be utilised to invite staff to participate in training, in order to maximise the use of training as an implementation strategy for obesity prevention in childcare services.

A novel quantification-driven proteomic strategy identifies an endogenous peptide of pleiotrophin as a new biomarker of Alzheimer's disease.

PubMed

Skillbäck, Tobias; Mattsson, Niklas; Hansson, Karl; Mirgorodskaya, Ekaterina; Dahlén, Rahil; van der Flier, Wiesje; Scheltens, Philip; Duits, Floor; Hansson, Oskar; Teunissen, Charlotte; Blennow, Kaj; Zetterberg, Henrik; Gobom, Johan

2017-10-17

We present a new, quantification-driven proteomic approach to identifying biomarkers. In contrast to the identification-driven approach, limited in scope to peptides that are identified by database searching in the first step, all MS data are considered to select biomarker candidates. The endopeptidome of cerebrospinal fluid from 40 Alzheimer's disease (AD) patients, 40 subjects with mild cognitive impairment, and 40 controls with subjective cognitive decline was analyzed using multiplex isobaric labeling. Spectral clustering was used to match MS/MS spectra. The top biomarker candidate cluster (215% higher in AD compared to controls, area under ROC curve = 0.96) was identified as a fragment of pleiotrophin located near the protein's C-terminus. Analysis of another cohort (n = 60 over four clinical groups) verified that the biomarker was increased in AD patients while no change in controls, Parkinson's disease or progressive supranuclear palsy was observed. The identification of the novel biomarker pleiotrophin 151-166 demonstrates that our quantification-driven proteomic approach is a promising method for biomarker discovery, which may be universally applicable in clinical proteomics.

Cost-effectiveness of alternative colonoscopy surveillance strategies to mitigate metachronous colorectal cancer incidence.

PubMed

Erenay, Fatih Safa; Alagoz, Oguzhan; Banerjee, Ritesh; Said, Adnan; Cima, Robert R

2016-08-15

The incidence of metachronous colorectal cancer (MCRC) among colorectal cancer (CRC) survivors varies significantly, and the optimal colonoscopy surveillance practice for mitigating MCRC incidence is unknown. A cost-effectiveness analysis was used to compare the performances of the US Multi-Society Task Force guideline and all clinically reasonable colonoscopy surveillance strategies for 50- to 79-year-old posttreatment CRC patients with a computer simulation model. The US guideline [(1,3,5)] recommends the first colonoscopy 1 year after treatment, whereas the second and third colonoscopies are to be repeated at 3- and 5-year intervals. Some promising alternative cost-effective strategies were identified. In comparison with the US guideline, under various scenarios for a 20-year period, 1) reducing the surveillance interval of the guideline after the first colonoscopy by 1 year [(1,2,5)] would save up to 78 discounted life-years (LYs) and prevent 23 MCRCs per 1000 patients (incremental cost-effectiveness ratio [ICER] ≤ $23,270/LY), 2) reducing the intervals after the first and second negative colonoscopies by 1 year [(1,2,4)] would save/prevent up to 109 discounted LYs and 36 MCRCs (ICER ≤ $52,155/LY), and 3) reducing the surveillance intervals after the first and second negative colonoscopy by 1 and 2 years [(1,2,3)] would save/prevent up to 141 discounted LYs and 50 MCRCs (ICER ≤ $63,822/LY). These strategies would require up to 1100 additional colonoscopies per 1000 patients. Although the US guideline might not be cost-effective in comparison with a less intensive oncology guideline [(3,3,5); the ICER could be as high as $140,000/LY], the promising strategies would be cost-effective in comparison with such less intensive guidelines unless the cumulative MCRC incidence were very low. The US guideline might be improved by a slight increase in the surveillance intensity at the expense of moderately increased cost. More research is warranted to explore the benefits/harms of such practices. Cancer 2016;122:2560-70. © 2016 American Cancer Society. © 2016 American Cancer Society.

Binge-eating disorder diagnosis and treatment: a recap in front of DSM-5.

PubMed

Amianto, Federico; Ottone, Luisa; Abbate Daga, Giovanni; Fassino, Secondo

2015-04-03

Binge Eating Disorders is a clinical syndrome recently coded as an autonomous diagnosis in DSM-5. Individuals affected by Binge Eating Disorder (BED) show significantly lower quality of life and perceived health and higher psychological distress compared to the non-BED obese population. BED treatment is complex due to clinical and psychological reasons but also to high drop-out and poor stability of achieved goals. The purpose of this review is to explore the available data on this topic, outlining the state-of-the-art on both diagnostic issues and most effective treatment strategies. We identified studies published in the last 6 years searching the MeSH Term "binge eating disorder", with specific regard to classification, diagnosis and treatment, in major computerized literature databases including: Medline, PubMed, PsychINFO and Science Direct. A total of 233 studies were found and, among them, 71 were selected and included in the review. Although Binge Eating Disorder diagnostic criteria showed empirical consistency, core psychopathology traits should be taken into account to address treatment strategies. The available body of evidence shows psychological treatments as first line interventions, even if their efficacy on weight loss needs further exploration. Behavioral and self-help interventions evidenced some efficacy in patients with lower psychopathological features. Pharmacological treatment plays an important role, but data are still limited by small samples and short follow-up times. The role of bariatric surgery, a recommended treatment for obesity that is often required also by patients with Binge Eating Disorder, deserves more specific studies. Combining different interventions at the same time does not add significant advantages, planning sequential treatments, with more specific interventions for non-responders, seems to be a more promising strategy. Despite its recent inclusion in DSM-5 as an autonomous disease, BED diagnosis and treatment strategies deserve further deepening. A multidisciplinary and stepped-care treatment appears as a promising management strategy. Longer and more structured follow-up studies are required, in order to enlighten long term outcomes and to overcome the high dropout rates affecting current studies.

Prediction of Chemical Respiratory Sensitizers Using GARD, a Novel In Vitro Assay Based on a Genomic Biomarker Signature

PubMed Central

Albrekt, Ann-Sofie; Borrebaeck, Carl A. K.; Lindstedt, Malin

2015-01-01

Background Repeated exposure to certain low molecular weight (LMW) chemical compounds may result in development of allergic reactions in the skin or in the respiratory tract. In most cases, a certain LMW compound selectively sensitize the skin, giving rise to allergic contact dermatitis (ACD), or the respiratory tract, giving rise to occupational asthma (OA). To limit occurrence of allergic diseases, efforts are currently being made to develop predictive assays that accurately identify chemicals capable of inducing such reactions. However, while a few promising methods for prediction of skin sensitization have been described, to date no validated method, in vitro or in vivo, exists that is able to accurately classify chemicals as respiratory sensitizers. Results Recently, we presented the in vitro based Genomic Allergen Rapid Detection (GARD) assay as a novel testing strategy for classification of skin sensitizing chemicals based on measurement of a genomic biomarker signature. We have expanded the applicability domain of the GARD assay to classify also respiratory sensitizers by identifying a separate biomarker signature containing 389 differentially regulated genes for respiratory sensitizers in comparison to non-respiratory sensitizers. By using an independent data set in combination with supervised machine learning, we validated the assay, showing that the identified genomic biomarker is able to accurately classify respiratory sensitizers. Conclusions We have identified a genomic biomarker signature for classification of respiratory sensitizers. Combining this newly identified biomarker signature with our previously identified biomarker signature for classification of skin sensitizers, we have developed a novel in vitro testing strategy with a potent ability to predict both skin and respiratory sensitization in the same sample. PMID:25760038

Monitoring positive mental health and its determinants in Canada: the development of the Positive Mental Health Surveillance Indicator Framework

PubMed Central

Orpana, H.; Vachon, J.; Dykxhoorn, J.; McRae, L.; Jayaraman, G.

2016-01-01

Abstract Introduction: The Mental Health Strategy for Canada identified a need to enhance the collection of data on mental health in Canada. While surveillance systems on mental illness have been established, a data gap for monitoring positive mental health and its determinants was identified. The goal of this project was to develop a Positive Mental Health Surveillance Indicator Framework, to provide a picture of the state of positive mental health and its determinants in Canada. Data from this surveillance framework will be used to inform programs and policies to improve the mental health of Canadians. Methods: A literature review and environmental scan were conducted to provide the theoretical base for the framework, and to identify potential positive mental health outcomes and risk and protective factors. The Public Health Agency of Canada’s definition of positive mental health was adopted as the conceptual basis for the outcomes of this framework. After identifying a comprehensive list of risk and protective factors, mental health experts, other governmental partners and non-governmental stakeholders were consulted to prioritize these indicators. Subsequently, these groups were consulted to identify the most promising measurement approaches for each indicator. Results: A conceptual framework for surveillance of positive mental health and its determinants has been developed to contain 5 outcome indicators and 25 determinant indicators organized within 4 domains at the individual, family, community and societal level. This indicator framework addresses a data gap identified in Canada’s strategy for mental health and will be used to inform programs and policies to improve the mental health status of Canadians throughout the life course. PMID:26789022

Strategies to circumvent the T315I gatekeeper mutation in the Bcr-Abl tyrosine kinase

PubMed Central

Bose, Prithviraj; Park, Haeseong; Al-Khafaji, Jawad; Grant, Steven

2013-01-01

Despite the remarkable success of imatinib against Bcr-Abl, development of secondary resistance, most often due to point mutations in the Bcr-Abl tyrosine kinase (TK) domain, is quite common. Of these, the T315I “gatekeeper” mutation is resistant to all currently registered Bcr-Abl TK inhibitors (TKIs) with the notable exception of ponatinib (Iclusig™), which was very recently approved by the United States Food and Drug Administration (FDA). Besides ponatinib, numerous strategies have been developed to circumvent this problem. These include the protein synthesis inhibitor omacetaxine (Synribo®), and “switch-control” inhibitors. Dual Bcr-Abl and aurora kinase inhibitors represent another promising strategy. Finally, several promising synergistic combinations, such as TKIs with histone deacetylase inhibitors (HDACIs), warrant attention. PMID:23977454

Diffusion and dissemination of evidence-based dietary strategies for the prevention of cancer.

PubMed

Ciliska, Donna; Robinson, Paula; Armour, Tanya; Ellis, Peter; Brouwers, Melissa; Gauld, Mary; Baldassarre, Fulvia; Raina, Parminder

2005-04-08

The purpose was to determine what strategies have been evaluated to disseminate cancer control interventions that promote the uptake of adult healthy diet? A systematic review was conducted. Studies were identified by searching MEDLINE, PREMEDLINE, Cancer LIT, EMBASE/Excerpta Medica, PsycINFO, CINAHL, the Cochrane Database of Systematic Reviews, and reference lists and by contacting technical experts. English-language primary studies were selected if they evaluated the dissemination of healthy diet interventions in individuals, healthcare providers, or institutions. Studies of children or adolescents only were excluded. One hundred one articles were retrieved for full text screening. Nine reports of seven distinct studies were included; four were randomized trials, one was a cohort design and three were descriptive studies. Six studies were rated as methodologically weak, and one was rated as moderate. Studies were not meta-analyzed because of heterogeneity, low methodological quality, and incomplete data reporting. No beneficial dissemination strategies were found except one that looks promising, the use of peer educators in the worksite, which led to a short-term increase in fruit and vegetable intake. Overall, the quality of the evidence is not strong and is primarily descriptive rather than evaluative. No clear conclusions can be drawn from these data. Controlled studies are needed to evaluate dissemination strategies, and to compare dissemination and diffusion strategies with different messages and different target audiences.

Identification of Strategies for Penetrating the 19-to-23-Year-Old Recruiting Market.

DTIC Science & Technology

1982-04-01

which the program might form the basis of an experimental marketing strategy . Information was also gathered on the Recruiting Resource Allocation Study...further examination of the potential relationship between these programs and Navy recruiting indicated that a marketing strategy built on this...as a marketing strategy for further development for the same reasons that CETA and Employment Service programs were not considered promising. 10 . .1w

On the sensitivity of geospatial low impact development locations to the centralized sewer network.

PubMed

Zischg, Jonatan; Zeisl, Peter; Winkler, Daniel; Rauch, Wolfgang; Sitzenfrei, Robert

2018-04-01

In the future, infrastructure systems will have to become smarter, more sustainable, and more resilient requiring new methods of urban infrastructure design. In the field of urban drainage, green infrastructure is a promising design concept with proven benefits to runoff reduction, stormwater retention, pollution removal, and/or the creation of attractive living spaces. Such 'near-nature' concepts are usually distributed over the catchment area in small scale units. In many cases, these above-ground structures interact with the existing underground pipe infrastructure, resulting in hybrid solutions. In this work, we investigate the effect of different placement strategies for low impact development (LID) structures on hydraulic network performance of existing drainage networks. Based on a sensitivity analysis, geo-referenced maps are created which identify the most effective LID positions within the city framework (e.g. to improve network resilience). The methodology is applied to a case study to test the effectiveness of the approach and compare different placement strategies. The results show that with a simple targeted LID placement strategy, the flood performance is improved by an additional 34% as compared to a random placement strategy. The developed map is easy to communicate and can be rapidly applied by decision makers when deciding on stormwater policies.

Clinical and Mechanistic Insights into the Genetics of Cardiomyopathy

PubMed Central

Burke, Michael A.; Cook, Stuart A.; Seidman, Jonathan G.; Seidman, Christine E.

2018-01-01

Over the last quarter-century, there has been tremendous progress in genetics research that has defined molecular causes for cardiomyopathies. More than a thousand mutations have been identified in many genes with varying ontologies, therein indicating the diverse molecules and pathways that cause hypertrophic, dilated, restrictive, and arrhythmogenic cardiomyopathies. Translation of this research to the clinic via genetic testing can precisely group affected patients according to molecular etiology, and identify individuals without evidence of disease who are at high risk for developing cardiomyopathy. These advances provide insights into the earliest manifestations of cardiomyopathy and help to define the molecular pathophysiological basis for cardiac remodeling. Although these efforts remain incomplete, new genomic technologies and analytic strategies provide unparalleled opportunities to fully explore the genetic architecture of cardiomyopathies. Such data hold the promise that mutation-specific pathophysiology will uncover novel therapeutic targets, and herald the beginning of precision therapy for cardiomyopathy patients. PMID:28007147

Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulation.

PubMed

Yang, Zijiang; Concannon, John; Ng, Kelvin S; Seyb, Kathleen; Mortensen, Luke J; Ranganath, Sudhir; Gu, Fangqi; Levy, Oren; Tong, Zhixiang; Martyn, Keir; Zhao, Weian; Lin, Charles P; Glicksman, Marcie A; Karp, Jeffrey M

2016-07-26

Pre-treatment or priming of mesenchymal stem cells (MSC) prior to transplantation can significantly augment the immunosuppressive effect of MSC-based therapies. In this study, we screened a library of 1402 FDA-approved bioactive compounds to prime MSC. We identified tetrandrine as a potential hit that activates the secretion of prostaglandin E2 (PGE2), a potent immunosuppressive agent, by MSC. Tetrandrine increased MSC PGE2 secretion through the NF-κB/COX-2 signaling pathway. When co-cultured with mouse macrophages (RAW264.7), tetrandrine-primed MSC attenuated the level of TNF-α secreted by RAW264.7. Furthermore, systemic transplantation of primed MSC into a mouse ear skin inflammation model significantly reduced the level of TNF-α in the inflamed ear, compared to unprimed cells. Screening of small molecules to pre-condition cells prior to transplantation represents a promising strategy to boost the therapeutic potential of cell therapy.

Electricity market design for the prosumer era

NASA Astrophysics Data System (ADS)

Parag, Yael; Sovacool, Benjamin K.

2016-04-01

Prosumers are agents that both consume and produce energy. With the growth in small and medium-sized agents using solar photovoltaic panels, smart meters, vehicle-to-grid electric automobiles, home batteries and other ‘smart’ devices, prosuming offers the potential for consumers and vehicle owners to re-evaluate their energy practices. As the number of prosumers increases, the electric utility sector of today is likely to undergo significant changes over the coming decades, offering possibilities for greening of the system, but also bringing many unknowns and risks that need to be identified and managed. To develop strategies for the future, policymakers and planners need knowledge of how prosumers could be integrated effectively and efficiently into competitive electricity markets. Here we identify and discuss three promising potential prosumer markets related to prosumer grid integration, peer-to-peer models and prosumer community groups. We also caution against optimism by laying out a series of caveats and complexities.

CEACAM1: Expression and Role in Melanocyte Transformation

PubMed Central

Turcu, Gabriela; Ion, Daniela Adriana; Brînzea, Alice; Cioplea, Mirela Daniela; Jilaveanu, Lucia Beatrice

2016-01-01

Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination. PMID:27642217

A screen to identify drug resistant variants to target-directed anti-cancer agents

PubMed Central

Azam, Mohammad; Raz, Tal; Nardi, Valentina; Opitz, Sarah L.

2003-01-01

The discovery of oncogenes and signal transduction pathways important for mitogenesis has triggered the development of target-specific small molecule anti-cancer compounds. As exemplified by imatinib (Gleevec), a specific inhibitor of the Chronic Myeloid Leukemia (CML)-associated Bcr-Abl kinase, these agents promise impressive activity in clinical trials, with low levels of clinical toxicity. However, such therapy is susceptible to the emergence of drug resistance due to amino acid substitutions in the target protein. Defining the spectrum of such mutations is important for patient monitoring and the design of next-generation inhibitors. Using imatinib and BCR/ABL as a paradigm for a drug-target pair, we recently reported a retroviral vector-based screening strategy to identify the spectrum of resistance-conferring mutations. Here we provide a detailed methodology for the screen, which can be generally applied to any drug-target pair. PMID:14615817

Dietary, food service, and mealtime interventions to promote food intake in acute care adult patients.

PubMed

Cheung, Grace; Pizzola, Lisa; Keller, Heather

2013-01-01

Malnutrition is common in acute care hospitals. During hospitalization, poor appetite, medical interventions, and food access issues can impair food intake leading to iatrogenic malnutrition. Nutritional support is a common intervention with demonstrated effectiveness. "Food first" approaches have also been developed and evaluated. This scoping review identified and summarized 35 studies (41 citations) that described and/or evaluated dietary, foodservice, or mealtime interventions with a food first focus. There were few randomized control trials. Individualized dietary treatment leads to improved food intake and other positive outcomes. Foodservices that promote point-of-care food selection are promising, but further research with food intake and nutritional outcomes is needed. Protected mealtimes have had insufficient implementation, leading to mixed results, while mealtime assistance, particularly provided by volunteers or dietary staff, appears to promote food intake. A few innovative strategies were identified but further research to develop and evaluate food first approaches is needed.

Communication technologies to improve HPV vaccination initiation and completion: A systematic review.

PubMed

Francis, Diane B; Cates, Joan R; Wagner, Kyla P Garrett; Zola, Tracey; Fitter, Jenny E; Coyne-Beasley, Tamera

2017-07-01

This systematic review examines the effectiveness of communication technology interventions on HPV vaccination initiation and completion. A comprehensive search strategy was used to identify existing randomized controlled trials testing the impact of computer-, mobile- or internet-based interventions on receipt of any dose of the HPV vaccine. Twelve relevant studies were identified with a total of 38,945 participants. The interventions were delivered using several different methods, including electronic health record (i.e. recall/reminder) prompts, text messaging, automated phone calls, interactive computer videos, and email. Vaccine initiation and completion was greater for technology-based studies relative to their control conditions. There is evidence that interventions utilizing communication technologies as their sole or primary mode for HPV vaccination intervention delivery may increase vaccination coverage. Communication technologies hold much promise for the future of HPV vaccination efforts, especially initiatives in practice-based settings. Copyright © 2017 Elsevier B.V. All rights reserved.

Discovery of potent and selective rhodanine type IKKβ inhibitors by hit-to-lead strategy.

PubMed

Song, Hyeseung; Lee, Yun Suk; Roh, Eun Joo; Seo, Jae Hong; Oh, Kwang-Seok; Lee, Byung Ho; Han, Hogyu; Shin, Kye Jung

2012-09-01

Regulation of NF-κB activation through the inhibition of IKKβ has been identified as a promising target for the treatment of inflammatory and autoimmune disease such as rheumatoid arthritis. In order to develop novel IKKβ inhibitors, we performed high throughput screening toward around 8000 library compounds, and identified a hit compound containing rhodanine moiety. We modified the structure of hit compound to obtain potent and selective IKKβ inhibitors. Throughout hit-to-lead studies, we have discovered optimized compounds which possess blocking effect toward NF-κB activation and TNFα production in cell as well as inhibition activity against IKKβ. Among them, compound 3q showed the potent inhibitory activity against IKKβ, and excellent selectivity over other kinases such as p38α, p38β, JNK1, JNK2, and JNK3 as well as IKKα. Copyright © 2012 Elsevier Ltd. All rights reserved.

Are we ready to use biomarkers for staging, prognosis and treatment selection in early-stage non-small-cell lung cancer?

PubMed

Massuti, Bartomeu; Sanchez, Jose Miguel; Hernando-Trancho, Florentino; Karachaliou, Niki; Rosell, Rafael

2013-06-01

Lung cancer accounts for the majority of cancer-related deaths worldwide. At present, platinum-based therapy represents the standard of care in fit stage II and IIIA non-small cell lung cancer (NSCLC) patients following surgical resection. In advanced disease, personalized chemotherapy and targeted biologic therapy based on histological and molecular tumor profiling have already shown promise in terms of optimizing treatment efficacy. While disease stage is associated with outcome and is commonly used to determine adjuvant treatment eligibility, it is known that a subset of patients with early stage disease experience shorter survival than others with the same clinicopathological characteristics. Improved methods for identifying these individuals, at or near the time of initial diagnosis, may inform the decision to pursue adjuvant therapy options. Among the numerous candidate molecular biomarkers, only few gene-expression profiling signatures provide clinically relevant information, while real-time quantitative polymerase-chain reaction (RT-qPCR) strategy involving relatively small numbers of genes offers a practical alternative with high cross-platform performance. mRNA and/or protein expression levels of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M subunit 1 (RRM1) and breast cancer susceptibility gene 1 (BRCA1) are among the most promising potential biomarkers for early disease and their clinical utility is currently being evaluated in randomized phase II and III clinical trials. This review describes the most promising clinicopathological and molecular biomarkers with predictive and prognostic significance in lung cancer that have been identified through advanced research and which could influence adjuvant and neoadjuvant chemotherapy decisions for operable NSCLC in routine clinical practice.

Genome-wide linkage scan for submaximal exercise heart rate in the HERITAGE family study.

PubMed

Spielmann, Nadine; Leon, Arthur S; Rao, D C; Rice, Treva; Skinner, James S; Rankinen, Tuomo; Bouchard, Claude

2007-12-01

The purpose of this study was to identify regions of the human genome linked to submaximal exercise heart rates in the sedentary state and in response to a standardized 20-wk endurance training program in blacks and whites of the HERITAGE Family Study. A total of 701 polymorphic markers covering the 22 autosomes were used in the genome-wide linkage scan, with 328 sibling pairs from 99 white nuclear families and 102 pairs from 115 black family units. Steady-state heart rates were measured at the relative intensity of 60% maximal oxygen uptake (HR60) and at the absolute intensity of 50 W (HR50). Baseline phenotypes were adjusted for age, sex, and baseline body mass index (BMI) and training responses (posttraining minus baseline, Delta) were adjusted for age, sex, baseline BMI, and baseline value of the phenotype. Two analytic strategies were used, a multipoint variance components and a regression-based multipoint linkage analysis. In whites, promising linkages (LOD > 1.75) were identified on 18q21-q22 for baseline HR50 (LOD = 2.64; P = 0.0002) and DeltaHR60 (LOD = 2.10; P = 0.0009) and on chromosome 2q33.3 for DeltaHR50 (LOD = 2.13; P = 0.0009). In blacks, evidence of promising linkage for baseline HR50 was detected with several markers within the chromosomal region 10q24-q25.3 (peak LOD = 2.43, P = 0.0004 with D10S597). The most promising regions for fine mapping in the HERITAGE Family Study were found on 2q33 for HR50 training response in whites, on 10q25-26 for baseline HR60 in blacks, and on 18q21-22 for both baseline HR50 and DeltaHR60 in whites.

Innovative Opioid Peptides and Biased Agonism: Novel Avenues for More Effective and Safer Analgesics to Treat Chronic Pain.

PubMed

Bedini, Andrea; Spampinato, Santi Mario

2017-02-15

Chronic pain is a clinically relevant and yet unsolved conditions that is poorly treated with the currently available drugs, thus highlighting the urgent need of innovative analgesics. Although opiates are not very effective in the treatment of inflammatory and neuropathic pain, developing novel opioid receptor peptide agonists, as well as modulating the opioid receptor-mediated responses in a ligand-specific fashion, may represent an innovative and promising strategy to identify more efficacious and safer antalgic drugs. In this review, novel analogues of endomorphin 1 (a mu opioid receptor selective agonist able to induce analgesia in different animal models of pain - including neuropathic pain) and dermorphin (one of the most potent opioid peptide existing in nature) will be discussed as they are emerging as a promising starting point to develop novel opioid agonists: endomorphin 1 analogues, in fact, may determine antinociception in different models of neuropathic pain with reduced side effects as compared to classic opiates as morphine; dermorphin analogues may elicit analgesia in animal models of both inflammatory and neuropathic pain and with less severe adverse effects. Furthermore, such opioid peptides may allow to explore unprecedented modalities of ligand-receptor interactions, helping to characterize biased agonism at opioid receptors: exploiting functional selectivity at opioid receptor may lead to identify innovative analgesic with improved pharmacological responses and optimized side effects. Thus, innovative opioid peptides, as those outlined in this review, are promising candidates to develop more effective opioid analgesics to be employed as medications for chronic pain states, as inflammatory or neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hombres Sanos: Evaluation of a Social Marketing Campaign for Heterosexually Identified Latino Men Who Have Sex With Men and Women

PubMed Central

Zellner, Jennifer A.; Sañudo, Fernando; Fernandez-Cerdeño, Araceli; Hovell, Melbourne F.; Sipan, Carol L.; Engelberg, Moshe; Carrillo, Hector

2010-01-01

Objectives. We evaluated the effectiveness of Hombres Sanos [Healthy Men] a social marketing campaign to increase condom use and HIV testing among heterosexually identified Latino men, especially among heterosexually identified Latino men who have sex with men and women (MSMW). Methods. Hombres Sanos was implemented in northern San Diego County, California, from June 2006 through December 2006. Every other month we conducted cross-sectional surveys with independent samples of heterosexually identified Latino men before (n = 626), during (n = 752), and after (n = 385) the campaign. Respondents were randomly selected from 12 targeted community venues to complete an anonymous, self-administered survey on sexual practices and testing for HIV and other sexually transmitted infections. About 5.6% of respondents (n = 98) were heterosexually identified Latino MSMW. Results. The intervention was associated with reduced rates of recent unprotected sex with both females and males among heterosexually identified Latino MSMW. The campaign was also associated with increases in perception of HIV risk, knowledge of testing locations, and condom carrying among heterosexual Latinos. Conclusions. Social marketing represents a promising approach for abating HIV transmission among heterosexually identified Latinos, particularly for heterosexually identified Latino MSMW. Given the scarcity of evidence-based HIV prevention interventions for these populations, this prevention strategy warrants further investigation. PMID:21068423

Hombres Sanos: evaluation of a social marketing campaign for heterosexually identified Latino men who have sex with men and women.

PubMed

Martínez-Donate, Ana P; Zellner, Jennifer A; Sañudo, Fernando; Fernandez-Cerdeño, Araceli; Hovell, Melbourne F; Sipan, Carol L; Engelberg, Moshe; Carrillo, Hector

2010-12-01

We evaluated the effectiveness of Hombres Sanos [Healthy Men] a social marketing campaign to increase condom use and HIV testing among heterosexually identified Latino men, especially among heterosexually identified Latino men who have sex with men and women (MSMW). Hombres Sanos was implemented in northern San Diego County, California, from June 2006 through December 2006. Every other month we conducted cross-sectional surveys with independent samples of heterosexually identified Latino men before (n = 626), during (n = 752), and after (n = 385) the campaign. Respondents were randomly selected from 12 targeted community venues to complete an anonymous, self-administered survey on sexual practices and testing for HIV and other sexually transmitted infections. About 5.6% of respondents (n = 98) were heterosexually identified Latino MSMW. The intervention was associated with reduced rates of recent unprotected sex with both females and males among heterosexually identified Latino MSMW. The campaign was also associated with increases in perception of HIV risk, knowledge of testing locations, and condom carrying among heterosexual Latinos. Social marketing represents a promising approach for abating HIV transmission among heterosexually identified Latinos, particularly for heterosexually identified Latino MSMW. Given the scarcity of evidence-based HIV prevention interventions for these populations, this prevention strategy warrants further investigation.

Real-World Strategies to Engage and Retain Racial-Ethnic Minority Young Men Who Have Sex with Men in HIV Prevention Services.

PubMed

Freese, Thomas E; Padwa, Howard; Oeser, Brandy T; Rutkowski, Beth A; Schulte, Marya T

2017-06-01

Racial/ethnic minority young men who have sex with men (YMSM)-particularly African Americans and Hispanics/Latinos-are at particularly high risk for HIV infection. Devising strategies to improve engagement and retention in HIV prevention services among minority YMSM is critical if the United States is going to achieve the National HIV/AIDS Strategy goal of reducing HIV health-related disparities. This article presents findings from a national summit on racial/ethnic YMSM services convened by the Substance Abuse and Mental Health Services Administration-funded Center of Excellence on Racial and Ethnic Minority Young Men Who Have Sex with Men and Other Lesbian, Gay, Bisexual, and Transgender Populations (YMSM + LGBT CoE) in September 2015. The summit included (1) subgroup discussions focused on issues related to treatment access, outreach/engagement/retention, continuing care/recovery support, and health literacy for minority YMSM; and (2) a ranking process, where the NIATx Nominal Group Technique was used to identify the strategies and approaches that summit participants believed to be most promising for engaging and retaining minority YMSM in HIV prevention services. Analyses of results from summit activities highlight four key cross-cutting strategies-utilizing peers, providing holistic care, making services fun, and utilizing technology-as critical for engaging minority YMSM in HIV prevention care. Examples of programs that utilize these strategies and implications of these findings for policy and practice are discussed.

Educational interventions to empower nursing home residents: a systematic literature review.

PubMed

Schoberer, Daniela; Leino-Kilpi, Helena; Breimaier, Helga E; Halfens, Ruud Jg; Lohrmann, Christa

2016-01-01

Health education is essential to improve health care behavior and self-management. However, educating frail, older nursing home residents about their health is challenging. Focusing on empowerment may be the key to educating nursing home residents effectively. This paper examines educational interventions that can be used to empower nursing home residents. A systematic literature search was performed of the databases PubMed, CINAHL, CENTRAL, PsycINFO, and Embase, screening for clinical trials that dealt with resident education and outcomes in terms of their ability to empower residents. An additional, manual search of the reference lists and searches with SIGLE and Google Scholar were conducted to identify gray literature. Two authors independently appraised the quality of the studies found and assigned levels to the evidence reported. The results of the studies were grouped according to their main empowering outcomes and described narratively. Out of 427 identified articles, ten intervention studies that addressed the research question were identified. The main educational interventions used were group education sessions, motivational and encouragement strategies, goal setting with residents, and the development of plans to meet defined goals. Significant effects on self-efficacy and self-care behavior were reported as a result of the interventions, which included group education and individual counseling based on resident needs and preferences. In addition, self-care behavior was observed to significantly increase in response to function-focused care and reasoning exercises. Perceptions and expectations were not improved by using educational interventions with older nursing home residents. Individually tailored, interactive, continuously applied, and structured educational strategies, including motivational and encouraging techniques, are promising interventions that can help nursing home residents become more empowered. Empowering strategies used by nurses can support residents in their growth and facilitate their self-determination. Further research on the empowerment of residents using empowerment scales is needed.

Navigating the currents of seascape genomics: how spatial analyses can augment population genomic studies

PubMed Central

Crandall, Eric D.; Liggins, Libby; Bongaerts, Pim; Treml, Eric A.

2016-01-01

Population genomic approaches are making rapid inroads in the study of non-model organisms, including marine taxa. To date, these marine studies have predominantly focused on rudimentary metrics describing the spatial and environmental context of their study region (e.g., geographical distance, average sea surface temperature, average salinity). We contend that a more nuanced and considered approach to quantifying seascape dynamics and patterns can strengthen population genomic investigations and help identify spatial, temporal, and environmental factors associated with differing selective regimes or demographic histories. Nevertheless, approaches for quantifying marine landscapes are complicated. Characteristic features of the marine environment, including pelagic living in flowing water (experienced by most marine taxa at some point in their life cycle), require a well-designed spatial-temporal sampling strategy and analysis. Many genetic summary statistics used to describe populations may be inappropriate for marine species with large population sizes, large species ranges, stochastic recruitment, and asymmetrical gene flow. Finally, statistical approaches for testing associations between seascapes and population genomic patterns are still maturing with no single approach able to capture all relevant considerations. None of these issues are completely unique to marine systems and therefore similar issues and solutions will be shared for many organisms regardless of habitat. Here, we outline goals and spatial approaches for landscape genomics with an emphasis on marine systems and review the growing empirical literature on seascape genomics. We review established tools and approaches and highlight promising new strategies to overcome select issues including a strategy to spatially optimize sampling. Despite the many challenges, we argue that marine systems may be especially well suited for identifying candidate genomic regions under environmentally mediated selection and that seascape genomic approaches are especially useful for identifying robust locus-by-environment associations. PMID:29491947

Navigating the currents of seascape genomics: how spatial analyses can augment population genomic studies.

PubMed

Riginos, Cynthia; Crandall, Eric D; Liggins, Libby; Bongaerts, Pim; Treml, Eric A

2016-12-01

Population genomic approaches are making rapid inroads in the study of non-model organisms, including marine taxa. To date, these marine studies have predominantly focused on rudimentary metrics describing the spatial and environmental context of their study region (e.g., geographical distance, average sea surface temperature, average salinity). We contend that a more nuanced and considered approach to quantifying seascape dynamics and patterns can strengthen population genomic investigations and help identify spatial, temporal, and environmental factors associated with differing selective regimes or demographic histories. Nevertheless, approaches for quantifying marine landscapes are complicated. Characteristic features of the marine environment, including pelagic living in flowing water (experienced by most marine taxa at some point in their life cycle), require a well-designed spatial-temporal sampling strategy and analysis. Many genetic summary statistics used to describe populations may be inappropriate for marine species with large population sizes, large species ranges, stochastic recruitment, and asymmetrical gene flow. Finally, statistical approaches for testing associations between seascapes and population genomic patterns are still maturing with no single approach able to capture all relevant considerations. None of these issues are completely unique to marine systems and therefore similar issues and solutions will be shared for many organisms regardless of habitat. Here, we outline goals and spatial approaches for landscape genomics with an emphasis on marine systems and review the growing empirical literature on seascape genomics. We review established tools and approaches and highlight promising new strategies to overcome select issues including a strategy to spatially optimize sampling. Despite the many challenges, we argue that marine systems may be especially well suited for identifying candidate genomic regions under environmentally mediated selection and that seascape genomic approaches are especially useful for identifying robust locus-by-environment associations.

Using Functional Signatures to Identify Repositioned Drugs for Breast, Myelogenous Leukemia and Prostate Cancer

PubMed Central

Shigemizu, Daichi; Hu, Zhenjun; Hung, Jui-Hung; Huang, Chia-Ling; Wang, Yajie; DeLisi, Charles

2012-01-01

The cost and time to develop a drug continues to be a major barrier to widespread distribution of medication. Although the genomic revolution appears to have had little impact on this problem, and might even have exacerbated it because of the flood of additional and usually ineffective leads, the emergence of high throughput resources promises the possibility of rapid, reliable and systematic identification of approved drugs for originally unintended uses. In this paper we develop and apply a method for identifying such repositioned drug candidates against breast cancer, myelogenous leukemia and prostate cancer by looking for inverse correlations between the most perturbed gene expression levels in human cancer tissue and the most perturbed expression levels induced by bioactive compounds. The method uses variable gene signatures to identify bioactive compounds that modulate a given disease. This is in contrast to previous methods that use small and fixed signatures. This strategy is based on the observation that diseases stem from failed/modified cellular functions, irrespective of the particular genes that contribute to the function, i.e., this strategy targets the functional signatures for a given cancer. This function-based strategy broadens the search space for the effective drugs with an impressive hit rate. Among the 79, 94 and 88 candidate drugs for breast cancer, myelogenous leukemia and prostate cancer, 32%, 13% and 17% respectively are either FDA-approved/in-clinical-trial drugs, or drugs with suggestive literature evidences, with an FDR of 0.01. These findings indicate that the method presented here could lead to a substantial increase in efficiency in drug discovery and development, and has potential application for the personalized medicine. PMID:22346740

Status of molten carbonate fuel cell technology development

NASA Astrophysics Data System (ADS)

Parsons, E. L., Jr.; Williams, M. C.; George, T. J.

The MCFC technology has been identified by the DOE as a promising product for commercialization. Development of the MCFC technology supports the National Energy Strategy. Review of the status of the MCFC technology indicates that the MCFC technology developers are making rapid and significant progress. Manufacturing facility development and extensive testing is occurring. Improvements in performance (power density), lower costs, improved packaging, and scale up to full height are planned. MCFC developers need to continue to be responsive to end-users in potential markets. It will be market demands for the correct product definition which will ultimately determine the character of MCFC power plants. There is a need for continued MCFC product improvement and multiple product development tests.

Advances in HIV Microbicide Development

PubMed Central

Olsen, Joanna S.; Easterhoff, David; Dewhurst, Stephen

2014-01-01

There is an urgent need for a way to control the spread of the global HIV pandemic. A microbicide, or topical drug applied to the mucosal environment to block transmission, is a promising HIV prevention strategy. The development of a safe and efficacious microbicide requires a thorough understanding of the mucosal environment and it's role in HIV transmission. Knowledge of the key events in viral infection identifies points at which the virus might be most effectively targeted by a microbicide. The cervicovaginal and rectal mucosa play an important role in the innate defense against HIV, and microbicides must not interfere with these functions. In this review we discuss the current research on HIV microbicide development. PMID:22098355

Animal models of traumatic brain injury

PubMed Central

Xiong, Ye; Mahmood, Asim; Chopp, Michael

2014-01-01

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in both civilian life and the battlefield worldwide. Survivors of TBI frequently experience long-term disabling changes in cognition, sensorimotor function and personality. Over the past three decades, animal models have been developed to replicate the various aspects of human TBI, to better understand the underlying pathophysiology and to explore potential treatments. Nevertheless, promising neuroprotective drugs, which were identified to be effective in animal TBI models, have all failed in phase II or phase III clinical trials. This failure in clinical translation of preclinical studies highlights a compelling need to revisit the current status of animal models of TBI and therapeutic strategies. PMID:23329160

Maintaining Sustainability for Green Schools

ERIC Educational Resources Information Center

Kennedy, Mike

2011-01-01

The promise of sustainably designed school facilities is that they will operate more efficiently and last longer than buildings constructed in more traditional ways. But that promise comes with a big if. The payoff is delivered only if the facility managers operate and maintain the buildings in ways that adhere to sustainable strategies called for…

Strategies for Success: Promising Ideas in Adult College Completion. Policy Exchanges

ERIC Educational Resources Information Center

Lane, Patrick

2012-01-01

This publication is the first of a series focusing on promising new ideas and innovative practices developed through the Adult College Completion Network. The brief addresses five topics of importance to those working to improve adult college completion: (1) Data availability particular to the returning adult population; (2) Partnerships between…

Pharmacophore Hybridization To Discover Novel Topoisomerase II Poisons with Promising Antiproliferative Activity.

PubMed

Ortega, Jose Antonio; Riccardi, Laura; Minniti, Elirosa; Borgogno, Marco; Arencibia, Jose M; Greco, Maria L; Minarini, Anna; Sissi, Claudia; De Vivo, Marco

2018-02-08

We used a pharmacophore hybridization strategy to combine key structural elements of merbarone and etoposide and generated new type II topoisomerase (topoII) poisons. This first set of hybrid topoII poisons shows promising antiproliferative activity on human cancer cells, endorsing their further exploration for anticancer drug discovery.

Improving medication adherence among kidney transplant recipients: Findings from other industries, patient engagement, and behavioral economics—A scoping review

PubMed Central

Oberlin, Shelley R; Parente, Stephen T; Pruett, Timothy L

2016-01-01

The immune system is a powerful barrier to successful organ transplantation, but one that has been routinely thwarted through modern pharmacotherapeutics. Despite the benefits of immunosuppressive therapy, medication non-adherence leads to an increased risk of graft rejection, higher hospital utilization and costs, and poor outcomes. We conduct a scoping review following Arksey and O’Malley’s five-stage framework methodology to identify established or novel interventions that could be applied to kidney transplant recipients to improve medication adherence. As the desired outcome is a behavior (taking a pill), we assess three areas: behavioral-focused interventions in other industries, patient engagement theories, and behavioral economic principles. Search strategies included mining business, social sciences, and medical literature with additional guidance from six consultative interviews. Our review suggests that no intervention stands out as superior or likely to be more effective than any other intervention; yet promising strategies and interventions were identified across all three areas examined. Based on our findings, we believe there are five strategies that transplant centers and other organizations can implement to improve medication adherence: (1) Build a foundation of trust; (2) Employ multiple interventions; (3) Stratify the population; (4) Develop collaborative partnerships; and (5) Embed medication adherence into the organization’s culture. The effectiveness of these interventions will need to be investigated further, but we believe they are a step in the right direction for organizations to consider in their efforts to improve medication adherence. PMID:26835016

Targeting BTK through microRNA in chronic lymphocytic leukemia

PubMed Central

Bottoni, Arianna; Rizzotto, Lara; Lai, Tzung-Huei; Liu, Chaomei; Smith, Lisa L.; Mantel, Rose; Reiff, Sean; El-Gamal, Dalia; Larkin, Karilyn; Johnson, Amy J.; Lapalombella, Rosa; Lehman, Amy; Plunkett, William; Byrd, John C.; Blachly, James S.; Woyach, Jennifer A.

2016-01-01

Bruton’s tyrosine kinase (BTK) is a critical mediator of survival in B-cell neoplasms. Although BTK inhibitors have transformed therapy in chronic lymphocytic leukemia (CLL), patients with high-risk genetics are at risk for relapse and have a poor prognosis. Identification of novel therapeutic strategies for this group of patients is an urgent unmet clinical need, and therapies that target BTK via alternative mechanisms may fill this niche. Herein, we identify a set of microRNAs (miRs) that target BTK in primary CLL cells and show that the histone deacetylase (HDAC) repressor complex is recruited to these miR promoters to silence their expression. Targeting the HDACs by using either RNA interference against HDAC1 in CLL or a small molecule inhibitor (HDACi) in CLL and mantle cell lymphoma restored the expression of the BTK-targeting miRs with loss of BTK protein and downstream signaling and consequent cell death. We have also made the novel and clinically relevant discovery that inhibition of HDAC induces the BTK-targeting miRs in ibrutinib-sensitive and resistant CLL to effectively reduce both wild-type and C481S-mutant BTK. This finding identifies a novel strategy that may be promising as a therapeutic modality to eliminate the C481S-mutant BTK clone that drives resistance to ibrutinib and provides the rationale for a combination strategy that includes ibrutinib to dually target BTK to suppress its prosurvival signaling. PMID:27756747

Targeting BTK through microRNA in chronic lymphocytic leukemia.

PubMed

Bottoni, Arianna; Rizzotto, Lara; Lai, Tzung-Huei; Liu, Chaomei; Smith, Lisa L; Mantel, Rose; Reiff, Sean; El-Gamal, Dalia; Larkin, Karilyn; Johnson, Amy J; Lapalombella, Rosa; Lehman, Amy; Plunkett, William; Byrd, John C; Blachly, James S; Woyach, Jennifer A; Sampath, Deepa

2016-12-29

Bruton's tyrosine kinase (BTK) is a critical mediator of survival in B-cell neoplasms. Although BTK inhibitors have transformed therapy in chronic lymphocytic leukemia (CLL), patients with high-risk genetics are at risk for relapse and have a poor prognosis. Identification of novel therapeutic strategies for this group of patients is an urgent unmet clinical need, and therapies that target BTK via alternative mechanisms may fill this niche. Herein, we identify a set of microRNAs (miRs) that target BTK in primary CLL cells and show that the histone deacetylase (HDAC) repressor complex is recruited to these miR promoters to silence their expression. Targeting the HDACs by using either RNA interference against HDAC1 in CLL or a small molecule inhibitor (HDACi) in CLL and mantle cell lymphoma restored the expression of the BTK-targeting miRs with loss of BTK protein and downstream signaling and consequent cell death. We have also made the novel and clinically relevant discovery that inhibition of HDAC induces the BTK-targeting miRs in ibrutinib-sensitive and resistant CLL to effectively reduce both wild-type and C481S-mutant BTK. This finding identifies a novel strategy that may be promising as a therapeutic modality to eliminate the C481S-mutant BTK clone that drives resistance to ibrutinib and provides the rationale for a combination strategy that includes ibrutinib to dually target BTK to suppress its prosurvival signaling. © 2016 by The American Society of Hematology.

Animal use replacement, reduction, and refinement: development of an integrated testing strategy for bioconcentration of chemicals in fish.

PubMed

de Wolf, Watze; Comber, Mike; Douben, Peter; Gimeno, Sylvia; Holt, Martin; Léonard, Marc; Lillicrap, Adam; Sijm, Dick; van Egmond, Roger; Weisbrod, Anne; Whale, Graham

2007-01-01

When addressing the use of fish for the environmental safety of chemicals and effluents, there are many opportunities for applying the principles of the 3Rs: Reduce, Refine, and Replace. The current environmental regulatory testing strategy for bioconcentration and secondary poisoning has been reviewed, and alternative approaches that provide useful information are described. Several approaches can be used to reduce the number of fish used in the Organization for Economic Cooperation and Development (OECD) Test Guideline 305, including alternative in vivo test methods such as the dietary accumulation test and the static exposure approach. The best replacement approach would seem to use read-across, chemical grouping, and quantitative structure-activity relationships with an assessment of the key processes in bioconcentration: Adsorption, distribution, metabolism, and excretion. Biomimetic extraction has particular usefulness in addressing bioavailable chemicals and is in some circumstances capable of predicting uptake. Use of alternative organisms such as invertebrates should also be considered. A single cut-off value for molecular weight and size beyond which no absorption will take place cannot be identified. Recommendations for their use in bioaccumulative (B) categorization schemes are provided. Assessment of biotransformation with in vitro assays and in silico approaches holds significant promise. Further research is needed to identify their variability and confidence limits and the ways to use this as a basis to estimate bioconcentration factors. A tiered bioconcentration testing strategy has been developed taking account of the alternatives discussed.

Barriers to medication adherence in asthma: the importance of culture and context.

PubMed

McQuaid, Elizabeth L

2018-03-23

Significant disparities exist in asthma outcomes. Racial and ethnic minorities have lower controller medication adherence, which may contribute to differences in asthma morbidity between minority and non-minority groups. The objective of this review is to identify individual, patient-provider communication, and systems issues that contribute to this pattern of medication underuse and to discuss potential strategies for intervention. Data were gathered from numerous sources, including reports of pharmacy and medical records, observational studies, and trials. Studies analyzed factors contributing to patterns of asthma medication adherence that differ by race and ethnicity. There is clear evidence of underuse of asthma controller medications among racial and ethnic minorities in prescription receipt, prescription initiation, and medication use once obtained. Individual factors such as medication beliefs and depressive symptoms play a role. Provider communication is also relevant, including limited discussion of Complementary and Alternative Medicine (CAM) use, difficulties communicating with patients and caregivers with limited English proficiency (LEP), and implicit biases regarding cultural differences. Systems issues (e.g., insurance status, cost) and social context factors (e.g. exposure to violence) also present challenges. Culturally-informed strategies that capitalize on patient strengths and training providers in culturally-informed communication strategies hold promise as intervention approaches. Disparities in controller medication use are pervasive. Identifying the sources of these disparities is a critical step toward generating intervention approaches to enhance disease management among the groups that bear the greatest asthma burden. Copyright © 2018. Published by Elsevier Inc.

Improving medication adherence among kidney transplant recipients: Findings from other industries, patient engagement, and behavioral economics-A scoping review.

PubMed

Oberlin, Shelley R; Parente, Stephen T; Pruett, Timothy L

2016-01-01

The immune system is a powerful barrier to successful organ transplantation, but one that has been routinely thwarted through modern pharmacotherapeutics. Despite the benefits of immunosuppressive therapy, medication non-adherence leads to an increased risk of graft rejection, higher hospital utilization and costs, and poor outcomes. We conduct a scoping review following Arksey and O'Malley's five-stage framework methodology to identify established or novel interventions that could be applied to kidney transplant recipients to improve medication adherence. As the desired outcome is a behavior (taking a pill), we assess three areas: behavioral-focused interventions in other industries, patient engagement theories, and behavioral economic principles. Search strategies included mining business, social sciences, and medical literature with additional guidance from six consultative interviews. Our review suggests that no intervention stands out as superior or likely to be more effective than any other intervention; yet promising strategies and interventions were identified across all three areas examined. Based on our findings, we believe there are five strategies that transplant centers and other organizations can implement to improve medication adherence: (1) Build a foundation of trust; (2) Employ multiple interventions; (3) Stratify the population; (4) Develop collaborative partnerships; and (5) Embed medication adherence into the organization's culture. The effectiveness of these interventions will need to be investigated further, but we believe they are a step in the right direction for organizations to consider in their efforts to improve medication adherence.

The motivation of health professionals to explore research evidence in their practice: An intervention study.

PubMed

Henderson, Amanda; Winch, Sarah; Holzhauser, Kerri; De Vries, Sue

2006-12-01

To assess the impact of multifaceted clinically focused educational strategies that concentrated on introducing dementia care research evidence on health professionals' awareness and inclination to use research findings in their future practice. The promise of evidence-based practice is slow to materialize with the limitations of adopting research findings in practice readily identifiable. A pre- and post-test quasi experimental design. The study involved the administration of: a pretest (baseline), an intervention phase, and a post-test survey, the same research utilization survey. TOOL: The Edmonton Research Orientation Survey (EROS), a self-report tool that asks participants about their attitudes toward research and about their potential to use research findings, was used to determine health professionals' orientation to research. The introduction of dementia care research evidence through multifaceted clinically focused educational strategies to improve practice. This was achieved through a resource team comprising a Clinical Nurse Consultant, as a leader and resource of localized evidence-based knowledge in aged care; an experienced Registered Nurse to support the introduction of strategies and a further experienced educator and clinician to reinforce the importance of evidence in change. Across all the four subscales that are measured in the Edmonton Research Orientation Survey, statistical analysis by independent samples t-test identified that there was no significant change between the before and after measurements. Successful integration of changes based on evidence does not necessarily mean that staff become more aware or are more inclined to use research findings in future to address problems.

Gliptins in managing diabetes - Reviewing computational strategy.

PubMed

Sneha, P; Doss, C George Priya

2016-12-01

The pace of anti-diabetic drug discovery is very slow in spite of increasing rate of prevalence of Type 2 Diabetes which remains a major public health concern. Though extensive research steps are taken in the past decade, yet craves for better new treatment strategies to overcome the current scenario. One such general finding is the evolution of gliptins which discriminately inhibits DPP4 (Dipeptidyl peptidase-4) enzyme. Although the mechanism of action of gliptin is highly target oriented and accurate, still its long-term use stands unknown. This step calls for a fast, flexible, and cost-effective strategies to meet the demands of producing arrays of high-content lead compounds with improved efficiency for better clinical success. The present review highlights the available gliptins in the market and also other naturally occurring DPP4 enzyme inhibitors. Along with describing the known inhibitors and their origin in this review, we attempted to identify a probable new lead compounds using advanced computational techniques. In this context, computational methods that integrate the knowledge of proteins and drug responses were utilized in prioritizing targets and designing drugs towards clinical trials with better efficacy. The compounds obtained as a result of virtual screening were compared with the commercially available gliptin in the market to have better efficiency in the identification and validation of the potential DPP4 inhibitors. The combinatorial computational methods used in the present study identified Compound 1: 25022354 as promising inhibitor. Copyright © 2016 Elsevier Inc. All rights reserved.

Mixed-linker strategy for the construction of multifunctional metal–organic frameworks

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

Qin, Jun-Sheng; Yuan, Shuai; Wang, Qi

2017-01-01

Mixed-linker strategy is a promising way to construct multifunctional metal–organic frameworks (MOFs). In this review, we demonstrate the recent developments, discussions and challenges related to the preparation and applications of four types of mixed-linker MOF materials.

"Turnaround" as Shock Therapy: Race, Neoliberalism, and School Reform

ERIC Educational Resources Information Center

Johnson, Amanda Walker

2013-01-01

"Turnaround" strategies of educational reform promise that school closure, reconstitution, privatizing, and reopening them will bring miraculous results. Questioning the implications, this article situates "turnaround" strategies locally, following the closure of a predominantly minority high school in 2008, in Austin, Texas.…

Prevention and treatment of low back pain: evidence, challenges, and promising directions.

PubMed

Foster, Nadine E; Anema, Johannes R; Cherkin, Dan; Chou, Roger; Cohen, Steven P; Gross, Douglas P; Ferreira, Paulo H; Fritz, Julie M; Koes, Bart W; Peul, Wilco; Turner, Judith A; Maher, Chris G

2018-06-09

Many clinical practice guidelines recommend similar approaches for the assessment and management of low back pain. Recommendations include use of a biopsychosocial framework to guide management with initial non-pharmacological treatment, including education that supports self-management and resumption of normal activities and exercise, and psychological programmes for those with persistent symptoms. Guidelines recommend prudent use of medication, imaging, and surgery. The recommendations are based on trials almost exclusively from high-income countries, focused mainly on treatments rather than on prevention, with limited data for cost-effectiveness. However, globally, gaps between evidence and practice exist, with limited use of recommended first-line treatments and inappropriately high use of imaging, rest, opioids, spinal injections, and surgery. Doing more of the same will not reduce back-related disability or its long-term consequences. The advances with the greatest potential are arguably those that align practice with the evidence, reduce the focus on spinal abnormalities, and ensure promotion of activity and function, including work participation. We have identified effective, promising, or emerging solutions that could offer new directions, but that need greater attention and further research to determine if they are appropriate for large-scale implementation. These potential solutions include focused strategies to implement best practice, the redesign of clinical pathways, integrated health and occupational interventions to reduce work disability, changes in compensation and disability claims policies, and public health and prevention strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gellan gum-based hydrogels for intervertebral disc tissue-engineering applications.

PubMed

Silva-Correia, J; Oliveira, J M; Caridade, S G; Oliveira, J T; Sousa, R A; Mano, J F; Reis, R L

2011-06-01

Intervertebral disc (IVD) degeneration is a challenging clinical problem that urgently demands viable nucleus pulposus (NP) implant materials. The best suited biomaterial for NP regeneration has yet to be identified, but it is believed that biodegradable hydrogel-based materials are promising candidates. In this work, we have developed ionic- and photo-crosslinked methacrylated gellan gum (GG-MA) hydrogels to be used in acellular and cellular tissue-engineering strategies for the regeneration of IVDs. The physicochemical properties of the developed hydrogels were investigated by Fourier-transform infrared spectroscopy, (1) H nuclear magnetic resonance and differential scanning calorimetry. The swelling ability and degradation rate of hydrogels were also analysed in phosphate-buffered saline solution at physiological pH for a period of 30 days. Additionally, the morphology and mechanical properties of the hydrogels were assessed under a scanning electron microscope and dynamic compression, respectively. An in vitro study was carried out to screen possible cytotoxicity of the gellan gum-based hydrogels by culturing rat lung fibroblasts (L929 cells) with hydrogel leachables up to 7 days. The results demonstrated that gellan gum was successfully methacrylated. We observed that the produced GG-MA hydrogels possess improved mechanical properties and lower water uptake ability and degradation rate as compared to gellan gum. This work also revealed that GG-MA hydrogels are non-cytotoxic in vitro, thus being promising biomaterials to be used in IVD tissue-engineering strategies. Copyright © 2010 John Wiley & Sons, Ltd.

PARP Inhibitors in Ovarian Cancer.

PubMed

Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Genta, Sofia; Aglietta, Massimo; Sapino, Anna; Valabrega, Giorgio

2018-03-05

Treatment of Epithelial Ovarian Cancer (EOC), historically based on surgery and platinum doublet chemotherapy, is associated with high risk of relapse and poor prognosis for recurrent disease. In this landscape, the innovative treatment with PARP inhibitors (PARPis) demonstrated an outstanding activity in EOC, and is currently changing clinical practice in BRCA mutant patients. To highlight the mechanism of action, pharmacokinetics, clinical activity, indications and current strategies of development of Olaparib, Niraparib, Rucaparib, Talazoparib and Veliparib, the 5 most relevant PARPis. We performed a review on Pubmed using 'ovarian cancer' and the name of each PARPi (PARP inhibitor) discussed in the review as Medical Subject Headings (MeSH) keywords. The same search was performed on "clinicaltrial.gov" to identify ongoing clinical trials and on "google.com/patents" and "uspto.gov" for recent patents exploring PARPIs in ovarian cancer. Olaparib, Niraparib and Rucaparib are already approved for treatment of recurrent EOC and their indications are partially overlapping. Talazoparib and Veliparib are promising PARPis, but currently under investigation in early phase trials. Several studies are evaluating PARPis in monotherapy or in associations, in a wide range of settings (i.e. first line, neoadjuvant, platinum-sensitive and resistant disease). PARPis are valuable options in patients with recurrent ovarian cancer with promising activity in different stages of this disease. Further studies are required to better define optimal clinical settings, predictors of response beyond BRCA mutations and strategies to overcome secondary resistance of PARPis therapy in EOC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A bird's-eye view of cell therapy and tissue engineering for cardiac regeneration.

PubMed

Soler-Botija, Carolina; Bagó, Juli R; Bayes-Genis, Antoni

2012-04-01

Complete recovery of ischemic cardiac muscle after myocardial infarction is still an unresolved concern. In recent years, intensive research efforts have focused on mimicking the physical and biological properties of myocardium for cardiac repair. Here we show how heart regeneration approaches have evolved from cell therapy to refined tissue engineering. Despite progressive improvements, the best cell type and delivery strategy are not well established. Our group has identified a new population of cardiac adipose tissue-derived progenitor cells with inherent cardiac and angiogenic potential that is a promising candidate for cell therapy to restore ischemic myocardium. We also describe results from three strategies for cell delivery into a murine model of myocardial infarction: intramyocardial injection, implantation of a fibrin patch loaded with cells, and an engineered bioimplant (a combination of chemically designed scaffold, peptide hydrogel, and cells); dual-labeling noninvasive bioluminescence imaging enables in vivo monitoring of cardiac-specific markers and cell survival. © 2012 New York Academy of Sciences.

Personalising exercise recommendations for brain health: considerations and future directions.

PubMed

Barha, Cindy K; Galea, Liisa A; Nagamatsu, Lindsay S; Erickson, Kirk I; Liu-Ambrose, Teresa

2017-04-01

The societal value of strategies that delay the onset and progression of dementia cannot be overstated. Physical activity-unstructured and structured-is a promising, cost-effective strategy for the promotion of brain health. However, a large degree of variation exists in its efficacy. Therefore, to increase its utility as 'medication' for healthy cognitive ageing, it is imperative to identify key moderators and mediators of the positive effects of targeted exercise training on brain health. In this commentary, we focus on the type of targeted exercise training, the determinants of individual variation, including biological sex and genotypic factors, and the mechanisms by which exercise exerts its influence on the brain. We argue that a better understanding of these factors will allow for evidence-based, personalised, tailored exercise recommendations that go beyond the one-size-fits-all approach to successfully combat dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Realizing the Promise of Chemical Glycobiology.

PubMed

Wang, Lai-Xi; Davis, Benjamin G

2013-09-01

Chemical glycobiology is emerging as one of the most uniquely powerful sub-disciplines of chemical biology. The previous scarcity of chemical strategies and the unparalleled structural diversity have created a uniquely fertile ground that is both rich in challenges and potentially very profound in implications. Glycans (oligosaccharides, polysaccharides, and glycoconjugates) are everywhere in biological systems and yet remain disproportionately neglected - reviews highlighting this 'Cinderella status' abound. Yet, the last two decades have witnessed tremendous progress, notably in chemical and chemoenzymatic synthesis, 'sequencing' and arraying, metabolic engineering and imaging. These vital steps serve to highlight not only the great potential but just how much more remains to be done. The vast chemical and functional space of glycans remains to be truly explored. Top-down full-scale glycomic and glycoproteomic studies coupled with hypothesis-driven, bottom-up innovative chemical strategies will be required to properly realize the potential impact of glycoscience on human health, energy, and economy. In this review, we cherry-pick far-sighted advances and use these to identify possible challenges, opportunities and avenues in chemical glycobiology.

The role of thioredoxin reductase 1 in melanoma metabolism and metastasis.

PubMed

Cassidy, Pamela B; Honeggar, Matthew; Poerschke, Robyn L; White, Karen; Florell, Scott R; Andtbacka, Robert H I; Tross, Joycelyn; Anderson, Madeleine; Leachman, Sancy A; Moos, Philip J

2015-11-01

Although significant progress has been made in targeted and immunologic therapeutics for melanoma, many tumors fail to respond, and most eventually progress when treated with the most efficacious targeted combination therapies thus far identified. Therefore, alternative approaches that exploit distinct melanoma phenotypes are necessary to develop new approaches for therapeutic intervention. Tissue microarrays containing human nevi and melanomas were used to evaluate levels of the antioxidant protein thioredoxin reductase 1 (TR1), which was found to increase as a function of disease progression. Melanoma cell lines revealed metabolic differences that correlated with TR1 levels. We used this new insight to design a model treatment strategy that creates a synthetic lethal interaction wherein targeting TR1 sensitizes melanoma to inhibition of glycolytic metabolism, resulting in a decrease in metastases in vivo. This approach holds the promise of a new clinical therapeutic strategy, distinct from oncoprotein inhibition. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A combined drama-based and CBT approach to working with self-reported anger aggression.

PubMed

Blacker, Janine; Watson, Andy; Beech, Anthony R

2008-01-01

A drama-based programme, called 'Insult to Injury', was designed to explore the processes of anger, aggression and violence. The aim of the programme was to enable offenders to identify and generate strategies and skills for dealing with potentially volatile situations, and to provide a safe and supportive environment in which to practice and evaluate these strategies. AIMS An active drama-based approach combined with cognitive-behavioural techniques was used to explore issues such as masculinity, power and control, pride and shame and victim awareness. Reductions in anger were hypothesized. METHOD A single group pre/post design assessed the levels of anger before and after the course. RESULTS Sixty-two adult male offenders from six prison establishments in the UK took part in the nine-day course. As hypothesised, significant reductions in anger were found in pre- to post-course assessment. These results suggest that a drama-based approach may be a promising adjunct to traditional anger management programmes for violent offenders.

Thinking outside the box - novel antibacterials to tackle the resistance crisis.

PubMed

Lakemeyer, Markus; Zhao, Weining; Mandl, Franziska A; Hammann, Peter; Sieber, Stephan Axel

2018-06-25

The public view on antibiotics as reliable medicine has changed when reports about "resistant superbugs" shattered the news. While reasons for this development are easily spotted, solutions for re-establishing effective antibiotics are still in their infancy. This review encompasses several aspects of the antibiotic development pipeline from very early strategies to mature drugs. We provide an interdisciplinary overview of methods suitable for mining novel antibiotics and discuss strategies to unravel their modes of action. Select examples of antibiotics recently identified using these platforms not only illustrate the efficiency of these measures, but also highlight promising clinical candidates with therapeutic potential. Furthermore, the concept of molecules that disarm pathogens by addressing gatekeepers of virulence will be covered. We conclude with an evaluation of antibacterials currently in clinical development. Overall, this review aims to connect select innovative antimicrobial approaches to stimulate interdisciplinary partnerships between chemists from academia and industry. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Repurposing the Saccharomyces cerevisiae peroxisome for compartmentalizing multi-enzyme pathways

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

DeLoache, William; Russ, Zachary; Samson, Jennifer

The peroxisome of Saccharomyces cerevisiae was targeted for repurposing in order to create a synthetic organelle that provides a generalizable compartment for engineered metabolic pathways. Compartmentalization of enzymes into organelles is a promising strategy for limiting metabolic crosstalk, improving pathway efficiency, and ultimately modifying the chemical environment to be distinct from that of the cytoplasm. We focused on the Saccharomyces cerevisiae peroxisome, as this organelle is not required for viability when grown on conventional media. We identified an enhanced peroxisomal targeting signal type 1 (PTS1) for rapidly importing non-native cargo proteins. Additionally, we performed the first systematic in vivo measurementsmore » of nonspecific metabolite permeability across the peroxisomal membrane using a polymer exclusion assay and characterized the size dependency of metabolite trafficking. Finally, we applied these new insights to compartmentalize a two-enzyme pathway in the peroxisome and characterize the expression regimes where compartmentalization leads to improved product titer. This work builds a foundation for using the peroxisome as a synthetic organelle, highlighting both promise and future challenges on the way to realizing this goal.« less

Advances in immunotherapy for the treatment of glioblastoma.

PubMed

Tivnan, Amanda; Heilinger, Tatjana; Lavelle, Ed C; Prehn, Jochen H M

2017-01-01

Glioblastoma (GBM) is an aggressive brain tumour, associated with extremely poor prognosis and although there have been therapeutic advances, treatment options remain limited. This review focuses on the use of immunotherapy, harnessing the power of the host's immune system to reject cancer cells. Key challenges in glioma specific immunotherapy as with many other cancers are the limited immunogenicity of the cancer cells and the immunosuppressive environment of the tumour. Although specific antigens have been identified in several cancers; brain tumours, such as GBM, are considered poorly immunogenic. However, as detailed in this review, strategies aimed at circumventing these challenges are showing promise for GBM treatment; including identification of glioma specific antigens and endogenous immune cell activation in an attempt to overcome the immunosuppressive environment which is associated with GBM tumours. An up-to-date summary of current Phase I/II and ongoing Phase III GBM immunotherapy clinical trials is provided in addition to insights into promising preclinical approaches which are focused predominantly on increased induction of Type 1 helper T cell (T h 1) immune responses within patients.

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

PubMed Central

Kao, Amy H.; Manzi, Susan; Ahearn, Joseph M.

2013-01-01

The search for lupus biomarkers to diagnose, monitor, stratify, and predict individual response to therapy is currently more intense than ever before. This effort is essential for several reasons. First, epidemic overdiagnosis and underdiagnosis of lupus, even by certified rheumatologists, leads to errors in therapy with concomitant side effects which may be more serious than the disease itself. Second, identification of lupus flares remains as much an art as it is a science. Third, the capacity to stratify patients so as to predict those who will develop specific patterns of organ involvement is not currently possible but would potentially lead to preventive therapeutic strategies. Fourth, only one new drug for the treatment of lupus has been approved by the US Food and Drug Administration in over 50 years. A major obstacle in this pipeline is the dearth of biomarkers available to prove a patient has responded to an experimental therapeutic intervention. This review will summarize the challenges faced in the discovery and validation of lupus biomarkers, the most promising lupus biomarkers identified to date, and the promise of future directions. PMID:23904865

Enhancement of Biomass and Lipid Productivities of Water Surface-Floating Microalgae by Chemical Mutagenesis

PubMed Central

Nojima, Daisuke; Ishizuka, Yuki; Muto, Masaki; Ujiro, Asuka; Kodama, Fumito; Yoshino, Tomoko; Maeda, Yoshiaki; Matsunaga, Tadashi; Tanaka, Tsuyoshi

2017-01-01

Water surface-floating microalgae have great potential for biofuel applications due to the ease of the harvesting process, which is one of the most problematic steps in conventional microalgal biofuel production. We have collected promising water surface-floating microalgae and characterized their capacity for biomass and lipid production. In this study, we performed chemical mutagenesis of two water surface-floating microalgae to elevate productivity. Floating microalgal strains AVFF007 and FFG039 (tentatively identified as Botryosphaerella sp. and Chlorococcum sp., respectively) were exposed to ethyl methane sulfonate (EMS) or 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), and pale green mutants (PMs) were obtained. The most promising FFG039 PM formed robust biofilms on the surface of the culture medium, similar to those formed by wild type strains, and it exhibited 1.7-fold and 1.9-fold higher biomass and lipid productivities than those of the wild type. This study indicates that the chemical mutation strategy improves the lipid productivity of water surface-floating microalgae without inhibiting biofilm formation and floating ability. PMID:28555001

Enhancement of Biomass and Lipid Productivities of Water Surface-Floating Microalgae by Chemical Mutagenesis.

PubMed

Nojima, Daisuke; Ishizuka, Yuki; Muto, Masaki; Ujiro, Asuka; Kodama, Fumito; Yoshino, Tomoko; Maeda, Yoshiaki; Matsunaga, Tadashi; Tanaka, Tsuyoshi

2017-05-27

Water surface-floating microalgae have great potential for biofuel applications due to the ease of the harvesting process, which is one of the most problematic steps in conventional microalgal biofuel production. We have collected promising water surface-floating microalgae and characterized their capacity for biomass and lipid production. In this study, we performed chemical mutagenesis of two water surface-floating microalgae to elevate productivity. Floating microalgal strains AVFF007 and FFG039 (tentatively identified as Botryosphaerella sp. and Chlorococcum sp., respectively) were exposed to ethyl methane sulfonate (EMS) or 1-methyl-3-nitro-1-nitrosoguanidine (MNNG), and pale green mutants (PMs) were obtained. The most promising FFG039 PM formed robust biofilms on the surface of the culture medium, similar to those formed by wild type strains, and it exhibited 1.7-fold and 1.9-fold higher biomass and lipid productivities than those of the wild type. This study indicates that the chemical mutation strategy improves the lipid productivity of water surface-floating microalgae without inhibiting biofilm formation and floating ability.

Anthropogenic Trace Compounds (ATCs) in aquatic habitats - research needs on sources, fate, detection and toxicity to ensure timely elimination strategies and risk management.

PubMed

Gerbersdorf, Sabine U; Cimatoribus, Carla; Class, Holger; Engesser, Karl-H; Helbich, Steffen; Hollert, Henner; Lange, Claudia; Kranert, Martin; Metzger, Jörg; Nowak, Wolfgang; Seiler, Thomas-Benjamin; Steger, Kristin; Steinmetz, Heidrun; Wieprecht, Silke

2015-06-01

Anthropogenic Trace Compounds (ATCs) that continuously grow in numbers and concentrations are an emerging issue for water quality in both natural and technical environments. The complex web of exposure pathways as well as the variety in the chemical structure and potency of ATCs represents immense challenges for future research and policy initiatives. This review summarizes current trends and identifies knowledge gaps in innovative, effective monitoring and management strategies while addressing the research questions concerning ATC occurrence, fate, detection and toxicity. We highlight the progressing sensitivity of chemical analytics and the challenges in harmonization of sampling protocols and methods, as well as the need for ATC indicator substances to enable cross-national valid monitoring routine. Secondly, the status quo in ecotoxicology is described to advocate for a better implementation of long-term tests, to address toxicity on community and environmental as well as on human-health levels, and to adapt various test levels and endpoints. Moreover, we discuss potential sources of ATCs and the current removal efficiency of wastewater treatment plants (WWTPs) to indicate the most effective places and elimination strategies. Knowledge gaps in transport and/or detainment of ATCs through their passage in surface waters and groundwaters are further emphasized in relation to their physico-chemical properties, abiotic conditions and biological interactions in order to highlight fundamental research needs. Finally, we demonstrate the importance and remaining challenges of an appropriate ATC risk assessment since this will greatly assist in identifying the most urgent calls for action, in selecting the most promising measures, and in evaluating the success of implemented management strategies. Copyright © 2015. Published by Elsevier Ltd.

Identification of Guanosine 5‧-diphosphate as Potential Iron Mobilizer: Preventing the Hepcidin-Ferroportin Interaction and Modulating the Interleukin-6/Stat-3 Pathway

NASA Astrophysics Data System (ADS)

Angmo, Stanzin; Tripathi, Neha; Abbat, Sheenu; Sharma, Shailesh; Singh, Shelley Sardul; Halder, Avishek; Yadav, Kamalendra; Shukla, Geeta; Sandhir, Rajat; Rishi, Vikas; Bharatam, Prasad V.; Yadav, Hariom; Singhal, Nitin Kumar

2017-01-01

Hepcidin, a peptide hormone, is a key regulator in mammalian iron homeostasis. Increased level of hepcidin due to inflammatory conditions stimulates the ferroportin (FPN) transporter internalization, impairing the iron absorption; clinically manifested as anemia of inflammation (AI). Inhibiting hepcidin-mediated FPN degradation is proposed as an important strategy to combat AI. A systematic approach involving in silico, in vitro, ex vivo and in vivo studies is employed to identify hepcidin-binding agents. The virtual screening of 68,752 natural compounds via molecular docking resulted into identification of guanosine 5‧-diphosphate (GDP) as a promising hepcidin-binding agent. The molecular dynamics simulations helped to identify the important hepcidin residues involved in stabilization of hepcidin-GDP complex. The results gave a preliminary indication that GDP may possibly inhibit the hepcidin-FPN interactions. The in vitro studies revealed that GDP caused FPN stabilization (FPN-GFP cell lines) and increased the FPN-mediated cellular iron efflux (HepG2 and Caco-2 cells). Interestingly, the co-administration of GDP and ferrous sulphate (FeSO4) ameliorated the turpentine-induced AI in mice (indicated by increased haemoglobin level, serum iron, FPN expression and decreased ferritin level). These results suggest that GDP a promising natural small-molecule inhibitor that targets Hepcidin-FPN complex may be incorporated with iron supplement regimens to ameliorate AI.

Hot-spot analysis to dissect the functional protein-protein interface of a tRNA-modifying enzyme.

PubMed

Jakobi, Stephan; Nguyen, Tran Xuan Phong; Debaene, François; Metz, Alexander; Sanglier-Cianférani, Sarah; Reuter, Klaus; Klebe, Gerhard

2014-10-01

Interference with protein-protein interactions of interfaces larger than 1500 Ų by small drug-like molecules is notoriously difficult, particularly if targeting homodimers. The tRNA modifying enzyme Tgt is only functionally active as a homodimer. Thus, blocking Tgt dimerization is a promising strategy for drug therapy as this protein is key to the development of Shigellosis. Our goal was to identify hot-spot residues which, upon mutation, result in a predominantly monomeric state of Tgt. The detailed understanding of the spatial location and stability contribution of the individual interaction hot-spot residues and the plasticity of motifs involved in the interface formation is a crucial prerequisite for the rational identification of drug-like inhibitors addressing the respective dimerization interface. Using computational analyses, we identified hot-spot residues that contribute particularly to dimer stability: a cluster of hydrophobic and aromatic residues as well as several salt bridges. This in silico prediction led to the identification of a promising double mutant, which was validated experimentally. Native nano-ESI mass spectrometry showed that the dimerization of the suggested mutant is largely prevented resulting in a predominantly monomeric state. Crystal structure analysis and enzyme kinetics of the mutant variant further support the evidence for enhanced monomerization and provide first insights into the structural consequences of the dimer destabilization. © 2014 Wiley Periodicals, Inc.

Identification of Guanosine 5′-diphosphate as Potential Iron Mobilizer: Preventing the Hepcidin-Ferroportin Interaction and Modulating the Interleukin-6/Stat-3 Pathway

PubMed Central

Angmo, Stanzin; Tripathi, Neha; Abbat, Sheenu; Sharma, Shailesh; Singh, Shelley Sardul; Halder, Avishek; Yadav, Kamalendra; Shukla, Geeta; Sandhir, Rajat; Rishi, Vikas; Bharatam, Prasad V.; Yadav, Hariom; Singhal, Nitin Kumar

2017-01-01

Hepcidin, a peptide hormone, is a key regulator in mammalian iron homeostasis. Increased level of hepcidin due to inflammatory conditions stimulates the ferroportin (FPN) transporter internalization, impairing the iron absorption; clinically manifested as anemia of inflammation (AI). Inhibiting hepcidin-mediated FPN degradation is proposed as an important strategy to combat AI. A systematic approach involving in silico, in vitro, ex vivo and in vivo studies is employed to identify hepcidin-binding agents. The virtual screening of 68,752 natural compounds via molecular docking resulted into identification of guanosine 5′-diphosphate (GDP) as a promising hepcidin-binding agent. The molecular dynamics simulations helped to identify the important hepcidin residues involved in stabilization of hepcidin-GDP complex. The results gave a preliminary indication that GDP may possibly inhibit the hepcidin-FPN interactions. The in vitro studies revealed that GDP caused FPN stabilization (FPN-GFP cell lines) and increased the FPN-mediated cellular iron efflux (HepG2 and Caco-2 cells). Interestingly, the co-administration of GDP and ferrous sulphate (FeSO4) ameliorated the turpentine-induced AI in mice (indicated by increased haemoglobin level, serum iron, FPN expression and decreased ferritin level). These results suggest that GDP a promising natural small-molecule inhibitor that targets Hepcidin-FPN complex may be incorporated with iron supplement regimens to ameliorate AI. PMID:28054602

An Assessment of the Oral Bioavailability of Three Ca-Channel Blockers Using a Cassette-Microdose Study: A New Strategy for Streamlining Oral Drug Development.

PubMed

Yamashita, Shinji; Kataoka, Makoto; Suzaki, Yuki; Imai, Hiromitsu; Morimoto, Takuya; Ohashi, Kyoichi; Inano, Akihiro; Togashi, Kazutaka; Mutaguchi, Kuninori; Sugiyama, Yuichi

2015-09-01

A cassette-microdose (MD) clinical study was performed to demonstrate its usefulness for identifying the most promising compound for oral use. Three Ca-channel blockers (nifedipine, nicardipine, and diltiazem) were chosen as model drugs. In the MD clinical study, a cassette-dose method was employed in which three model drugs were administered simultaneously. Both intravenous (i.v.) and oral (p.o.) administration studies were conducted to calculate the oral bioavailability (BA). For comparison, p.o. studies with therapeutic dose (ThD) levels were also performed. In all studies, blood concentrations of each drug were successfully determined using liquid chromatography-mass spectrometry with the lower limit of quantification of 0.2-2.0 pg/mL. Oral BA of nifedipine in the MD study was approximately 50% and in the same range with that obtained in the ThD study, whereas other two drugs showed significantly lower BA in the MD study, indicating a dose-dependent absorption. In addition, compared with the ThD study, absorption of nicardipine was delayed in the MD study. As a result, nifedipine was considered to be most promising for oral use. In conclusion, a cassette-MD clinical study is of advantage for oral drug development that enables to identify the candidate having desired properties for oral use. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Salmonella Growth and Deposition Inside Eggs: Implications for Refrigeration as a Control Strategy

USDA-ARS?s Scientific Manuscript database

A recent risk assessment for Salmonella Enteritidis contamination of eggs concluded that prompt refrigeration of freshly laid eggs was among the most promising disease mitigation strategies. ARS research has provided detailed information about the deposition, movement, and multiplication of Salmonel...

What are the most promising strategies for the therapeutic immunomodulation of allergic diseases?

PubMed

Tokura, Y; Röcken, M; Clark, R A; Haliasos, E; Takigawa, M; Sinha, A A

2001-04-01

Specific immunotherapy and other immunomodulatory strategies have long been a stronghold in the management of allergic diseases. In particular, "immunodeviation-therapy" or "vaccination for allergies", i.e. the redirection of Th2-type immune responses towards a Th1-response pattern, has become an ever more popular concept. The present feature of CONTROVERSIES complements our previous discussion of atopy (Röcken et al., Exp Dermatol 7: 97--104, 1998), and is dedicated to a critical analysis of the general problems and limitations one faces with the main immunomodulatory strategies traditionally considered in this context. We also explore alternative approaches that appear promising in order to achieve both a more effective and/or a more specific immunotherapy of allergic diseases. Given that the mast cell remains a key protagonist in the pathogenesis of allergic diseases finally, this feature examines how innovative, more selectively mast cell-targeted strategies may be developed for the management of allergic diseases.

Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”

PubMed Central

Gomes, Nelson G. M.; Dasari, Ramesh; Chandra, Sunena; Kiss, Robert; Kornienko, Alexander

2016-01-01

Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors’ opinion should be pursued due to their most promising anticancer activities. PMID:27213412

Porous AgPt@Pt Nanooctahedra as an Efficient Catalyst toward Formic Acid Oxidation with Predominant Dehydrogenation Pathway.

PubMed

Jiang, Xian; Yan, Xiaoxiao; Ren, Wangyu; Jia, Yufeng; Chen, Jianian; Sun, Dongmei; Xu, Lin; Tang, Yawen

2016-11-16

For direct formic acid fuel cells (DFAFCs), the dehydrogenation pathway is a desired reaction pathway, to boost the overall cell efficiency. Elaborate composition tuning and nanostructure engineering provide two promising strategies to design efficient electrocatalysts for DFAFCs. Herein, we present a facile synthesis of porous AgPt bimetallic nanooctahedra with enriched Pt surface (denoted as AgPt@Pt nanooctahedra) by a selective etching strategy. The smart integration of geometric and electronic effect confers a substantial enhancement of desired dehydrogenation pathway as well as electro-oxidation activity for the formic acid oxidation reaction (FAOR). We anticipate that the obtained nanocatalyst may hold great promises in fuel cell devices, and furthermore, the facile synthetic strategy demonstrated here can be extendable for the fabrication of other multicomponent nanoalloys with desirable morphologies and enhanced electrocatalytic performances.

Late-life suicide prevention strategies: current status and future directions.

PubMed

Van Orden, Kim; Deming, Charlene

2017-09-08

Late life suicide prevention differs from suicide prevention for other age groups: first, the number of older adults worldwide is on the rise; second, late-life suicide receives much less attention in all societal spheres, from the media, to federal funding agencies, to healthcare initiatives. Recent findings indicate an association between internalized ageist stereotypes and reduced will to live. Recent research also addresses the role of cognitive control as a contributor to risk and as an intervention target (e.g., through psychotherapies such as problem solving therapy) as well as firearm safety as a promising, though a politicized and challenging strategy to implement. Another strategy that may prove feasible is an approach on upstream prevention strategies in healthcare. One strategy we believe holds great promise is the promotion of high quality geriatric medicine. Geriatricians are trained to work with patients to prioritize the promotion of physical and cognitive functioning (rather than solely absence of disease) and to focus on well-being as a goal. Thus, geriatricians routinely target numerous late-life suicide risk factors-physical illness, functioning, pain, and (dis)satisfaction with life. However, efficacious strategies will not prevent suicide deaths if they are not implemented-addressing ageism as a universal prevention strategy is essential. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of designed site-directed pseudopeptide-peptido-mimetic immunogens as novel minimal subunit-vaccine candidates for malaria.

PubMed

Lozano, José Manuel; Lesmes, Liliana P; Carreño, Luisa F; Gallego, Gina M; Patarroyo, Manuel Elkin

2010-12-06

Synthetic vaccines constitute the most promising tools for controlling and preventing infectious diseases. When synthetic immunogens are designed from the pathogen native sequences, these are normally poorly immunogenic and do not induce protection, as demonstrated in our research. After attempting many synthetic strategies for improving the immunogenicity properties of these sequences, the approach consisting of identifying high binding motifs present in those, and then performing specific changes on amino-acids belonging to such motifs, has proven to be a workable strategy. In addition, other strategies consisting of chemically introducing non-natural constraints to the backbone topology of the molecule and modifying the α-carbon asymmetry are becoming valuable tools to be considered in this pursuit. Non-natural structural constraints to the peptide backbone can be achieved by introducing peptide bond isosters such as reduced amides, partially retro or retro-inverso modifications or even including urea motifs. The second can be obtained by strategically replacing L-amino-acids with their enantiomeric forms for obtaining both structurally site-directed designed immunogens as potential vaccine candidates and their Ig structural molecular images, both having immuno-therapeutic effects for preventing and controlling malaria.

Disclosure, Apology, and Offer Programs: Stakeholders' Views of Barriers to and Strategies for Broad Implementation

PubMed Central

Bell, Sigall K; Smulowitz, Peter B; Woodward, Alan C; Mello, Michelle M; Duva, Anjali Mitter; Boothman, Richard C; Sands, Kenneth

2012-01-01

Context The Disclosure, Apology, and Offer (DA&O) model, a response to patient injuries caused by medical care, is an innovative approach receiving national attention for its early success as an alternative to the existing inherently adversarial, inefficient, and inequitable medical liability system. Examples of DA&O programs, however, are few. Methods Through key informant interviews, we investigated the potential for more widespread implementation of this model by provider organizations and liability insurers, defining barriers to implementation and strategies for overcoming them. Our study focused on Massachusetts, but we also explored themes that are broadly generalizable to other states. Findings We found strong support for the DA&O model among key stakeholders, who cited its benefits for both the liability system and patient safety. The respondents did not perceive any insurmountable barriers to broad implementation, and they identified strategies that could be pursued relatively quickly. Such solutions would permit a range of organizations to implement the model without legislative hurdles. Conclusions Although more data are needed about the outcomes of DA&O programs, the model holds considerable promise for transforming the current approach to medical liability and patient safety. PMID:23216427

Stem cells in sepsis and acute lung injury.

PubMed

Cribbs, Sushma K; Matthay, Michael A; Martin, Greg S

2010-12-01

Sepsis and acute lung injury continue to be major causes of morbidity and mortality worldwide despite advances in our understanding of pathophysiology and the discovery of new management strategies. Recent investigations show that stem cells may be beneficial as prognostic biomarkers and novel therapeutic strategies in these syndromes. This article reviews the potential use of endogenous adult tissue-derived stem cells in sepsis and acute lung injury as prognostic markers and also as exogenous cell-based therapy. A directed systematic search of the medical literature using PubMed and OVID, with particular emphasis on the time period after 2002, was done to evaluate topics related to 1) the epidemiology and pathophysiology of sepsis and acute lung injury; and 2) the definition, characterization, and potential use of stem cells in these diseases. DATA SYNTHESIS AND FINDINGS: When available, preferential consideration was given to prospective nonrandomized clinical and preclinical studies. Stem cells have shown significant promise in the field of critical care both for 1) prognostic value and 2) treatment strategies. Although several recent studies have identified the potential benefit of stem cells in sepsis and acute lung injury, further investigations are needed to more completely understand stem cells and their potential prognostic and therapeutic value.

Disclosure, apology, and offer programs: stakeholders' views of barriers to and strategies for broad implementation.

PubMed

Bell, Sigall K; Smulowitz, Peter B; Woodward, Alan C; Mello, Michelle M; Duva, Anjali Mitter; Boothman, Richard C; Sands, Kenneth

2012-12-01

The Disclosure, Apology, and Offer (DA&O) model, a response to patient injuries caused by medical care, is an innovative approach receiving national attention for its early success as an alternative to the existing inherently adversarial, inefficient, and inequitable medical liability system. Examples of DA&O programs, however, are few. Through key informant interviews, we investigated the potential for more widespread implementation of this model by provider organizations and liability insurers, defining barriers to implementation and strategies for overcoming them. Our study focused on Massachusetts, but we also explored themes that are broadly generalizable to other states. We found strong support for the DA&O model among key stakeholders, who cited its benefits for both the liability system and patient safety. The respondents did not perceive any insurmountable barriers to broad implementation, and they identified strategies that could be pursued relatively quickly. Such solutions would permit a range of organizations to implement the model without legislative hurdles. Although more data are needed about the outcomes of DA&O programs, the model holds considerable promise for transforming the current approach to medical liability and patient safety. © 2012 Milbank Memorial Fund.

Novel dual small-molecule HIV inhibitors: scaffolds and discovery strategies.

PubMed

Song, Anran; Yu, Haiqing; Wang, Changyuan; Zhu, Xingqi; Liu, Kexin; Ma, Xiaodong

2015-01-01

Searching for safe and effective treatments for HIV infection is still a great challenge worldwide in spite of the 27 marketed anti-HIV drugs and the powerful highly active antiretroviral therapy (HAART). As a promising prospect for generation of new HIV therapy drugs, multiple ligands (MDLs) were greatly focused on recently due to their lower toxicity, simplified dosing and patient adherence than single-target drugs. Till now, by disrupting two active sites or steps of HIV replications, a number of HIV dual inhibitors, such as CD4-gssucap120 inhibitors, CXCR4-gp20 inhibitors, RT-CXCR4 inhibitors, RT-protease inhibitors, RT-integrase inhibitors, and RTassociated functions inhibitors have been identified. Generally, these dual inhibitors were discovered mainly through screening approaches and design strategies. Of these compounds, the molecules bearing small skeletons exhibited strong anti-HIV activity and aroused great attention recently. Reviewing the progress of the dual small-molecule HIV inhibitors from the point of view of their scaffolds and discovery strategies will provide valuable information for producing more effective anti-HIV drugs. In this regard, novel dual small-molecule HIV inhibitors were illustrated, and their discovery paradigms as the major contents were also summarized in this manuscript.

A Qualitative Meta-Synthesis of Interpersonal Violence Prevention Programs Focused on Males.

PubMed

Taliep, Naiema; Lazarus, Sandy; Naidoo, Anthony V

2017-12-01

Exceptionally high levels of interpersonal violence have triggered a call by many experts for the need to determine effective ways to address the onset and effects of exposure to interpersonal violence. The specific aim of this study was to identify and draw on existing promising practices to make a more informed decision on strategies to develop a contextually relevant intervention that focused on the promotion of positive forms of masculinity to create safety and peace. This study used a qualitative meta-synthesis (QMS) technique to integrate and interpret findings from various intervention studies that focused on males and/or gender. An in-depth literature search yielded a total of 827 papers that met the search criteria. After removal of duplicates, abstract review, and review of the full texts, the subsequent sample for this meta-synthesis included 12 intervention programs and 23 studies. This QMS revealed the value of a comprehensive approach, using multiple strategies, employing participatory and interactive methods, and promoting social mobilization to address interpersonal violence. The promotion of positive forms of masculinity as an interpersonal violence prevention strategy is a much-needed, relatively untapped approach to generating safety and peace for both males and females.

The promise and challenge of practice-research collaborations: Guiding principles and strategies for initiating, designing, and implementing program evaluation research.

PubMed

Secret, Mary; Abell, Melissa L; Berlin, Trey

2011-01-01

The authors present a set of guiding principles and strategies to facilitate the collaborative efforts of social work researchers and practitioners as they initiate, design, and implement outcome evaluations of human service interventions and programs. Beginning with an exploration of the interpersonal barriers to practice-research collaborations, and building on their experiences in successfully completing a community-based research evaluation, the authors identify specific relationship-focused principles and strategies and illustrate how these approaches can guide practice-research teams through the various sequential activities of the evaluation research process. In particular, it is suggested that practice-research collaborations can be formed, strengthened, and sustained by emphasis on a spirit of discovery and shared leadership at the start of the relationship, use of a comprehensive evaluation model to clarify and frame the evaluation and program goals, beginning where the client is when selecting research methodology and measurement tools, commitment to keeping the program first and recording everything during the implementation and data-collection stages, discussion of emerging findings and presentation of findings in graphic format at the data-analysis stage, and a total team approach at the dissemination stage.

The elite young athlete: strategies to ensure physical and emotional health

PubMed Central

Sabato, Todd M; Walch, Tanis J; Caine, Dennis J

2016-01-01

This article presents a current review of the risk of physical and psychological injury associated with participation in elite youth sport, and suggests strategies to ensure the physical and emotional health of these young athletes. Although there is lack of epidemiological data, especially with regard to psychological injury, preliminary data suggest that the risk of injury is high in this population. While there is lack of incident and follow-up data, there is also concern regarding burnout, disordered eating, and the long-term consequences of injury. Modifiable injury risk factors identified include postural control, competition anxiety, life events, previous injury, and volume of training. There are presently no studies designed to determine the effectiveness of injury prevention measures in elite youth sports. However, there is adequate evidence arising from injury prevention studies of youth sports participants – including neuromuscular training, protective equipment, mental training to enhance self-esteem, and sport rules modification – to prevent injuries in elite youth sports settings. Although not tested, psychosocial prevention strategies such as adoption of task-oriented coping mechanisms, autonomous support from parents, and a proactive organizational approach also show promise in injury prevention. PMID:27621677

From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins.

PubMed

Verdes, Aida; Anand, Prachi; Gorson, Juliette; Jannetti, Stephen; Kelly, Patrick; Leffler, Abba; Simpson, Danny; Ramrattan, Girish; Holford, Mandë

2016-04-19

Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics methodologies, including genomics, transcriptomics, and proteomics; (3) chemical and recombinant synthesis of promising peptide toxins; (4) structural characterization through experimental and computational methods; (5) determination of teretoxin bioactivity and molecular function through biological assays and computational modeling; (6) optimization of peptide toxin affinity and selectivity to molecular target; and (7) development of strategies for effective delivery of venom peptide therapeutics. While our research focuses on terebrids, the venomics approach outlined here can be applied to the discovery and characterization of peptide toxins from any venomous taxa.

Understanding the effectiveness of the entertainment-education strategy: an investigation of how audience involvement, message processing, and message design influence health information recall.

PubMed

Quintero Johnson, Jessie M; Harrison, Kristen; Quick, Brian L

2013-01-01

A growing body of evidence suggests that entertainment-education (EE) is a promising health communication strategy. The purpose of this study was to identify some of the factors that facilitate and hinder audience involvement with EE messages. Using confirmatory factor analysis, the authors introduce a construct they call experiential involvement, which describes the experience of being cognitively and emotionally involved with EE messages and is a product of transportation into an EE text and identification with EE characters. Using an experimental design, the authors also investigated how reports of experiential involvement and health information recall varied depending on the degree to which the educational content was well integrated with the narrative content in EE messages. Findings indicated that integration significantly influenced health information recall. Results indicated that experiential involvement and the perception that the health topic in EE messages was personally relevant predicted participants' systematic processing of the information in EE messages. Contrary to expectation, personal relevance did not predict experiential involvement, and systematic message processing was negatively related to health information recall. Implications for the construction of EE messages and the study of the EE strategy are discussed.

Lighting and vegetation for energy-efficient and safe roadway travel.

DOT National Transportation Integrated Search

2009-04-01

The objective of the present study was to identify and evaluate promising approaches to incorporating : lighting and vegetation along roadways with the purpose of identifying the most promising application that : could be incorporated into a demonstr...

CONVERGENT TRANSCRIPTOMICS AND PROTEOMICS OF ENVIRONMENTAL ENRICHMENT AND COCAINE IDENTIFIES NOVEL THERAPEUTIC STRATEGIES FOR ADDICTION

PubMed Central

ZHANG, YAFANG; CROFTON, ELIZABETH J.; FAN, XIUZHEN; LI, DINGGE; KONG, FANPING; SINHA, MALA; LUXON, BRUCE A.; SPRATT, HEIDI M.; LICHTI, CHERYL F.; GREEN, THOMAS A.

2016-01-01

Transcriptomic and proteomic approaches have separately proven effective at identifying novel mechanisms affecting addiction-related behavior; however, it is difficult to prioritize the many promising leads from each approach. A convergent secondary analysis of proteomic and transcriptomic results can glean additional information to help prioritize promising leads. The current study is a secondary analysis of the convergence of recently published separate transcriptomic and proteomic analyses of nucleus accumbens (NAc) tissue from rats subjected to environmental enrichment vs. isolation and cocaine self-administration vs. saline. Multiple bioinformatics approaches (e.g. Gene Ontology (GO) analysis, Ingenuity Pathway Analysis (IPA), and Gene Set Enrichment Analysis (GSEA)) were used to interrogate these rich data sets. Although there was little correspondence between mRNA vs. protein at the individual target level, good correspondence was found at the level of gene/protein sets, particularly for the environmental enrichment manipulation. These data identify gene sets where there is a positive relationship between changes in mRNA and protein (e.g. glycolysis, ATP synthesis, translation elongation factor activity, etc.) and gene sets where there is an inverse relationship (e.g. ribosomes, Rho GTPase signaling, protein ubiquitination, etc.). Overall environmental enrichment produced better correspondence than cocaine self-administration. The individual targets contributing to mRNA and protein effects were largely not overlapping. As a whole, these results confirm that robust transcriptomic and proteomic data sets can provide similar results at the gene/protein set level even when there is little correspondence at the individual target level and little overlap in the targets contributing to the effects. PMID:27717806

PROspective Multicenter Imaging Study for Evaluation of chest pain: rationale and design of the PROMISE trial.

PubMed

Douglas, Pamela S; Hoffmann, Udo; Lee, Kerry L; Mark, Daniel B; Al-Khalidi, Hussein R; Anstrom, Kevin; Dolor, Rowena J; Kosinski, Andrzej; Krucoff, Mitchell W; Mudrick, Daniel W; Patel, Manesh R; Picard, Michael H; Udelson, James E; Velazquez, Eric J; Cooper, Lawton

2014-06-01

Suspected coronary artery disease (CAD) is one of the most common, potentially life-threatening diagnostic problems clinicians encounter. However, no large outcome-based randomized trials have been performed to guide the selection of diagnostic strategies for these patients. The PROMISE study is a prospective, randomized trial comparing the effectiveness of 2 initial diagnostic strategies in patients with symptoms suspicious for CAD. Patients are randomized to either (1) functional testing (exercise electrocardiogram, stress nuclear imaging, or stress echocardiogram) or (2) anatomical testing with ≥64-slice multidetector coronary computed tomographic angiography. Tests are interpreted locally in real time by subspecialty certified physicians, and all subsequent care decisions are made by the clinical care team. Sites are provided results of central core laboratory quality and completeness assessment. All subjects are followed up for ≥1 year. The primary end point is the time to occurrence of the composite of death, myocardial infarction, major procedural complications (stroke, major bleeding, anaphylaxis, and renal failure), or hospitalization for unstable angina. More than 10,000 symptomatic subjects were randomized in 3.2 years at 193 US and Canadian cardiology, radiology, primary care, urgent care, and anesthesiology sites. Multispecialty community practice enrollment into a large pragmatic trial of diagnostic testing strategies is both feasible and efficient. The PROMISE trial will compare the clinical effectiveness of an initial strategy of functional testing against an initial strategy of anatomical testing in symptomatic patients with suspected CAD. Quality of life, resource use, cost-effectiveness, and radiation exposure will be assessed. Copyright © 2014 Mosby, Inc. All rights reserved.

Promising Practices in Young Adult Employment: Hands-On Multidisciplinary Career Exploration and Mentorships

ERIC Educational Resources Information Center

Wagner, Stacey

2015-01-01

The National Fund for Workforce Solution's Young Adult Initiatives aim to test and implement new strategies for targeting America's young adults and share this information so that employers and workforce development can join forces in investing in the millions of young adults across the nation. This case study focuses on promising findings from…

Promising Practices in Young Adult Employment: Lessons Learned from Manufacturing and Automotive Career Pathway Programs

ERIC Educational Resources Information Center

Wagner, Stacey

2015-01-01

The National Fund's Young Adult Initiatives aim to test and implement new strategies for targeting America's young adults and share this information so that employers and workforce development can join forces in investing in the millions of young adults across the nation. This case study focuses on promising findings from automotive and…

Different Routes for Conifer- and Sinapaldehyde and Higher Saccharification upon Deficiency in the Dehydrogenase CAD1.

PubMed

Van Acker, Rebecca; Déjardin, Annabelle; Desmet, Sandrien; Hoengenaert, Lennart; Vanholme, Ruben; Morreel, Kris; Laurans, Françoise; Kim, Hoon; Santoro, Nicholas; Foster, Cliff; Goeminne, Geert; Légée, Frédéric; Lapierre, Catherine; Pilate, Gilles; Ralph, John; Boerjan, Wout

2017-11-01

In the search for renewable energy sources, genetic engineering is a promising strategy to improve plant cell wall composition for biofuel and bioproducts generation. Lignin is a major factor determining saccharification efficiency and, therefore, is a prime target to engineer. Here, lignin content and composition were modified in poplar ( Populus tremula × Populus alba ) by specifically down-regulating CINNAMYL ALCOHOL DEHYDROGENASE1 ( CAD1 ) by a hairpin-RNA-mediated silencing approach, which resulted in only 5% residual CAD1 transcript abundance. These transgenic lines showed no biomass penalty despite a 10% reduction in Klason lignin content and severe shifts in lignin composition. Nuclear magnetic resonance spectroscopy and thioacidolysis revealed a strong increase (up to 20-fold) in sinapaldehyde incorporation into lignin, whereas coniferaldehyde was not increased markedly. Accordingly, ultra-high-performance liquid chromatography-mass spectrometry-based phenolic profiling revealed a more than 24,000-fold accumulation of a newly identified compound made from 8-8 coupling of two sinapaldehyde radicals. However, no additional cinnamaldehyde coupling products could be detected in the CAD1-deficient poplars. Instead, the transgenic lines accumulated a range of hydroxycinnamate-derived metabolites, of which the most prominent accumulation (over 8,500-fold) was observed for a compound that was identified by purification and nuclear magnetic resonance as syringyl lactic acid hexoside. Our data suggest that, upon down-regulation of CAD1 , coniferaldehyde is converted into ferulic acid and derivatives, whereas sinapaldehyde is either oxidatively coupled into S'(8-8)S' and lignin or converted to sinapic acid and derivatives. The most prominent sink of the increased flux to hydroxycinnamates is syringyl lactic acid hexoside. Furthermore, low-extent saccharification assays, under different pretreatment conditions, showed strongly increased glucose (up to +81%) and xylose (up to +153%) release, suggesting that down-regulating CAD1 is a promising strategy for improving lignocellulosic biomass for the sugar platform industry. © 2017 American Society of Plant Biologists. All Rights Reserved.

Different Routes for Conifer- and Sinapaldehyde and Higher Saccharification upon Deficiency in the Dehydrogenase CAD11[OPEN

PubMed Central

Laurans, Françoise; Foster, Cliff; Légée, Frédéric

2017-01-01

In the search for renewable energy sources, genetic engineering is a promising strategy to improve plant cell wall composition for biofuel and bioproducts generation. Lignin is a major factor determining saccharification efficiency and, therefore, is a prime target to engineer. Here, lignin content and composition were modified in poplar (Populus tremula × Populus alba) by specifically down-regulating CINNAMYL ALCOHOL DEHYDROGENASE1 (CAD1) by a hairpin-RNA-mediated silencing approach, which resulted in only 5% residual CAD1 transcript abundance. These transgenic lines showed no biomass penalty despite a 10% reduction in Klason lignin content and severe shifts in lignin composition. Nuclear magnetic resonance spectroscopy and thioacidolysis revealed a strong increase (up to 20-fold) in sinapaldehyde incorporation into lignin, whereas coniferaldehyde was not increased markedly. Accordingly, ultra-high-performance liquid chromatography-mass spectrometry-based phenolic profiling revealed a more than 24,000-fold accumulation of a newly identified compound made from 8-8 coupling of two sinapaldehyde radicals. However, no additional cinnamaldehyde coupling products could be detected in the CAD1-deficient poplars. Instead, the transgenic lines accumulated a range of hydroxycinnamate-derived metabolites, of which the most prominent accumulation (over 8,500-fold) was observed for a compound that was identified by purification and nuclear magnetic resonance as syringyl lactic acid hexoside. Our data suggest that, upon down-regulation of CAD1, coniferaldehyde is converted into ferulic acid and derivatives, whereas sinapaldehyde is either oxidatively coupled into S′(8-8)S′ and lignin or converted to sinapic acid and derivatives. The most prominent sink of the increased flux to hydroxycinnamates is syringyl lactic acid hexoside. Furthermore, low-extent saccharification assays, under different pretreatment conditions, showed strongly increased glucose (up to +81%) and xylose (up to +153%) release, suggesting that down-regulating CAD1 is a promising strategy for improving lignocellulosic biomass for the sugar platform industry. PMID:28878036

Self-monitoring Lifestyle Behavior in Overweight and Obese Pregnant Women: Qualitative Findings.

PubMed

Shieh, Carol; Draucker, Claire Burke

Excessive maternal gestational weight gain increases pregnancy and infant complications. Self-monitoring has been shown to be an effective strategy in weight management. Literature, however, is limited in describing pregnant women's engagement in self-monitoring. This qualitative study explored the experiences of overweight and obese pregnant women who self-monitored their eating, walking, and weight as participants in an intervention for excessive gestational weight gain prevention. Thirteen overweight and obese pregnant women participated in semistructured interviews. Reflexive iteration data analysis was conducted. Five themes were identified: making self-monitoring a habit, strategies for self-monitoring, barriers to self-monitoring, benefits of self-monitoring, and drawbacks of self-monitoring. The women viewed self-monitoring as a "habit" that could foster a sense of self-control and mindfulness. Visual or tracing aids were used to maintain the self-monitoring habit. Forgetting, defective tracking aids, complexities of food monitoring, and life events could impede self-monitoring. Being unable to keep up with self-monitoring or to achieve goals created stress. Self-monitoring is a promising approach to weight management for overweight and obese pregnant women. However, healthcare providers should be aware that, although women may identify several benefits to self-monitoring, for some women, consistently trying to track their behaviors is stressful.

Emerging biomarkers in anaplastic oligodendroglioma: implications for clinical investigation and patient management.

PubMed

Sahebjam, Solmaz; McNamara, Mairéad G; Mason, Warren P

2013-07-01

Oligodendrogliomas are heterogeneous tumors with a variable response to treatment. This clinical variability underlines the urgent need for markers that can reliably aid diagnosis and guide clinical decision-making. Long-term follow-up data from the EORTC 26951 and RTOG 9402 clinical trials in newly diagnosed anaplastic oligodendroglioma have established chromosome 1p19q codeletion as a predictive marker of response to procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendrogliomas. In addition, MGMT promoter hypermethylation has been strongly associated with glioma CpG island hypermethylation phenotype (G-CIMP+) status, this has been suggested as an epiphenomenon of genome-wide methylation, conferring a more favorable prognosis. Molecular profiling of these tumors has identified several other markers with potential clinical significance: mutations of IDH, CIC, FUBP1 and CDKN2A require further validation before they can be implemented as clinical decision-making tools. Additionally, recent data on the clinical significance of intrinsic glioma subtyping appears promising. Indeed, existing evidence suggests that comprehensive analyses such as intrinsic glioma subtyping or G-CIMP status are superior to single molecular markers. Clearly, with evolving treatment strategies and in the era of individualized therapy, broader omics-based molecular evaluations are required to improve outcome prediction and to identify patients who will benefit from specific treatment strategies.

What roles do middle managers play in implementation of innovative practices?

PubMed Central

Engle, Ryann L.; Lopez, Emily R.; Gormley, Katelyn E.; Chan, Jeffrey A.; Charns, Martin P.; Lukas, Carol VanDeusen

2017-01-01

Background: Middle managers play key roles in hospitals as the bridge between senior leaders and frontline staff. Yet relatively little research has focused on their role in implementing new practices. Purpose: The aim of this study was to expand the understanding of middle managers’ influence in organizations by looking at their activities through the lens of two complementary conceptual frameworks. Methodology/Approach: We analyzed qualitative data from 17 Veterans Affairs Medical Centers with high and low potential to change organizational practices. We analyzed 98 interviews with staff ranging from senior leaders to frontline staff to identify themes within an a priori framework reflecting middle manager activities. Findings: Analyses yielded 14 emergent themes that allowed us to classify specific expressions of middle manager commitment to implementation of innovative practices (e.g., facilitate improvement innovation, garner staff buy-in). In comparing middle manager behaviors in high and low change potential sites, we found that most emergent themes were present in both groups. However, the activities and interactions described differed between the groups. Practice Implications: Middle managers can use the promising strategies identified by our analyses to guide and improve their effectiveness in implementing new practices. These strategies can also inform senior leaders striving to guide middle managers in those efforts. PMID:26488239

Systematic approach identifies RHOA as a potential biomarker therapeutic target for Asian gastric cancer.

PubMed

Chang, Hae Ryung; Nam, Seungyoon; Lee, Jinhyuk; Kim, Jin-Hee; Jung, Hae Rim; Park, Hee Seo; Park, Sungjin; Ahn, Young Zoo; Huh, Iksoo; Balch, Curt; Ku, Ja-Lok; Powis, Garth; Park, Taesung; Jeong, Jin-Hyun; Kim, Yon Hui

2016-12-06

Gastric cancer (GC) is a highly heterogeneous disease, in dire need of specific, biomarker-driven cancer therapies. While the accumulation of cancer "Big Data" has propelled the search for novel molecular targets for GC, its specific subpathway and cellular functions vary from patient to patient. In particular, mutations in the small GTPase gene RHOA have been identified in recent genome-wide sequencing of GC tumors. Moreover, protein overexpression of RHOA was reported in Chinese populations, while RHOA mutations were found in Caucasian GC tumors. To develop evidence-based precision medicine for heterogeneous cancers, we established a systematic approach to integrate transcriptomic and genomic data. Predicted signaling subpathways were then laboratory-validated both in vitro and in vivo, resulting in the identification of new candidate therapeutic targets. Here, we show: i) differences in RHOA expression patterns, and its pathway activity, between Asian and Caucasian GC tumors; ii) in vitro and in vivo perturbed RHOA expression inhibits GC cell growth in high RHOA-expressing cell lines; iii) inverse correlation between RHOA and RHOB expression; and iv) an innovative small molecule design strategy for RHOA inhibitors. In summary, RHOA, and its oncogenic signaling pathway, represent a strong biomarker-driven therapeutic target for Asian GC. This comprehensive strategy represents a promising approach for the development of "hit" compounds.

Targeting cancer stem-like cells in glioblastoma and colorectal cancer through metabolic pathways.

PubMed

Kahlert, U D; Mooney, S M; Natsumeda, M; Steiger, H-J; Maciaczyk, J

2017-01-01

Cancer stem-like cells (CSCs) are thought to be the main cause of tumor occurrence, progression and therapeutic resistance. Strong research efforts in the last decade have led to the development of several tailored approaches to target CSCs with some very promising clinical trials underway; however, until now no anti-CSC therapy has been approved for clinical use. Given the recent improvement in our understanding of how onco-proteins can manipulate cellular metabolic networks to promote tumorigenesis, cancer metabolism research may well lead to innovative strategies to identify novel regulators and downstream mediators of CSC maintenance. Interfering with distinct stages of CSC-associated metabolics may elucidate novel, more efficient strategies to target this highly malignant cell population. Here recent discoveries regarding the metabolic properties attributed to CSCs in glioblastoma (GBM) and malignant colorectal cancer (CRC) were summarized. The association between stem cell markers, the response to hypoxia and other environmental stresses including therapeutic insults as well as developmentally conserved signaling pathways with alterations in cellular bioenergetic networks were also discussed. The recent developments in metabolic imaging to identify CSCs were also summarized. This summary should comprehensively update basic and clinical scientists on the metabolic traits of CSCs in GBM and malignant CRC. © 2016 UICC.

Optimising the combination dosing strategy of abemaciclib and vemurafenib in BRAF-mutated melanoma xenograft tumours.

PubMed

Tate, Sonya C; Burke, Teresa F; Hartman, Daisy; Kulanthaivel, Palaniappan; Beckmann, Richard P; Cronier, Damien M

2016-03-15

Resistance to BRAF inhibition is a major cause of treatment failure for BRAF-mutated metastatic melanoma patients. Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, overcomes this resistance in xenograft tumours and offers a promising drug combination. The present work aims to characterise the quantitative pharmacology of the abemaciclib/vemurafenib combination using a semimechanistic pharmacokinetic/pharmacodynamic modelling approach and to identify an optimum dosing regimen for potential clinical evaluation. A PK/biomarker model was developed to connect abemaciclib/vemurafenib concentrations to changes in MAPK and cell cycle pathway biomarkers in A375 BRAF-mutated melanoma xenografts. Resultant tumour growth inhibition was described by relating (i) MAPK pathway inhibition to apoptosis, (ii) mitotic cell density to tumour growth and, under resistant conditions, (iii) retinoblastoma protein inhibition to cell survival. The model successfully described vemurafenib/abemaciclib-mediated changes in MAPK pathway and cell cycle biomarkers. Initial tumour shrinkage by vemurafenib, acquisition of resistance and subsequent abemaciclib-mediated efficacy were successfully captured and externally validated. Model simulations illustrate the benefit of intermittent vemurafenib therapy over continuous treatment, and indicate that continuous abemaciclib in combination with intermittent vemurafenib offers the potential for considerable tumour regression. The quantitative pharmacology of the abemaciclib/vemurafenib combination was successfully characterised and an optimised, clinically-relevant dosing strategy was identified.

Highly Efficient Oxygen-Storage Material with Intrinsic Coke Resistance for Chemical Looping Combustion-Based CO2 Capture.

PubMed

Imtiaz, Qasim; Kurlov, Alexey; Rupp, Jennifer Lilia Marguerite; Müller, Christoph Rüdiger

2015-06-22

Chemical looping combustion (CLC) and chemical looping with oxygen uncoupling (CLOU) are emerging thermochemical CO2 capture cycles that allow the capture of CO2 with a small energy penalty. Here, the development of suitable oxygen carrier materials is a key aspect to transfer these promising concepts to practical installations. CuO is an attractive material for CLC and CLOU because of its high oxygen-storage capacity (20 wt %), fast reaction kinetics, and high equilibrium partial pressure of oxygen at typical operating temperatures (850-1000 °C). However, despite its promising characteristics, its low Tammann temperature requires the development of new strategies to phase-stabilize CuO-based oxygen carriers. In this work, we report a strategy based on stabilization by co-precipitated ceria (CeO2-x ), which allowed us to increase the oxygen capacity, coke resistance, and redox stability of CuO-based oxygen carriers substantially. The performance of the new oxygen carriers was evaluated in detail and compared to the current state-of-the-art materials, that is, Al2 O3 -stabilized CuO with similar CuO loadings. We also demonstrate that the higher intrinsic oxygen uptake, release, and mobility in CeO2-x -stabilized CuO leads to a three times higher carbon deposition resistance compared to that of Al2 O3 -stabilized CuO. Moreover, we report a high cyclic stability without phase intermixing for CeO2-x -supported CuO. This was accompanied by a lower reduction temperature compared to state-of-the-art Al2 O3 -supported CuO. As a result of its high resistance towards carbon deposition and fast oxygen uncoupling kinetics, CeO2-x -stabilized CuO is identified as a very promising material for CLC- and CLOU-based CO2 capture architectures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PS2-10: The CRN Cancer Communication Research Center

PubMed Central

Madrid, Sarah D; Dearing, James W; Glasgow, Russell E; Rabin, Borsika A; Mazor, Kathleen; Wagner, Edward H

2010-01-01

We propose an integrated set of three, large posters that will describe the main components of a new research center that bridges HMORN institutions. Background: The CRN Cancer Communication Research Center (CCRC) was established in September 2008 at Kaiser Colorado Institute for Health Research. Objectives: The CCRC’s objectives are to discover the most promising practice-based approaches to cancer communication and care coordination, and to disseminate those approaches. Integrated care delivery systems represent promising opportunities to study these approaches, and the CRN CCRC, with its embedded organizational focus will take advantage of the CRN as a virtual laboratory. Specific Aims: The CRN CCRC 1) leverages the existing infrastructure of the CRN to support both the discovery and dissemination of practice-based communication strategies and organizational resources; 2) supports four investigator-initiated research projects to advance communication theory and to evaluate strategies informed by theory; and 3) provides administrative, financial, and scientific support to new investigators, including clinicians, in the development of pilot projects, and assists in submission of broader, investigator-initiated proposals to be submitted for extramural funding. Methods: Two R01-scale investigator initiated research projects will advance and test communication theory. The first will: characterize patients’ and providers’ experiences communicating about errors in cancer care; investigate the health system factors that promote or inhibit effective communication; and develop, disseminate, and evaluate provider training materials and patient informational materials. The second will develop and test an intervention to decrease patient uncertainty and improve psychosocial and communicative outcomes during the period from suspicion of cancer through diagnosis and plan of care. The Center’s research projects will be augmented and supported by Shared Resource Cores. The Discovery Core will identify the most promising practicebased innovations and approaches; the Dissemination Core will focus on data harmonization and applying dissemination science to effective interventions.

Diversification strategy and performance: implications for health services research.

PubMed

Rivers, P A; Glover, S H; Munchus, G

1999-01-01

Health care represents a promising area of research due to its uniqueness. In recent years, considerable progress has been made in diversification strategy and performance research but not the study of health services strategy research. This article reviews diversification strategy and performance in health services domains. Adopting Datta, Rajagopalan, and Rasheed's (1991) framework, the authors evaluate the theoretical and empirical contributions of this research. The limitations and theoretical implications of these efforts are also explored.

America Promises to Come Back: Our New National Security Strategy

DTIC Science & Technology

1991-10-23

Captain Larry Seaquist, U.S. Navy, Office of the Principal Deputy Under Secretary of Defense (Strategy and Resources); Vice Admiral James Service...to be primarily based on U.S. forces in being. Under the new national security strategy, deterrence of the Soviet threat will largely be based upon a...Cheney’s IISS remarks were followed by I. Lewis "Scooter" Libby, Principal Deputy Under Secretary of Defense (Strategy and Resources), who provided

Rural Cross-Sector Collaboration: A Social Frontier Analysis

ERIC Educational Resources Information Center

Miller, Peter M.; Scanlan, Martin K.; Phillippo, Kate

2017-01-01

Schools throughout the United States apply comprehensive community partnership strategies to address students' in- and out-of-school needs. Drawing from models like the Harlem Children's Zone, Promise Neighborhoods, and full-service community schools, such strategies call for diverse professionals to reach beyond their own organizations to…

Deficit irrigation effects on yield and yield components of grain sorghum

USDA-ARS?s Scientific Manuscript database

Development of sustainable and efficient irrigation strategies is a priority for producers faced with water shortages. A promising management strategy for improving water use efficiency (WUE) is managed deficit irrigation (MDI), which attempts to optimize yield and WUE by synchronizing crop water u...

Web conferencing in online classrooms.

PubMed

Hart, Leigh

2014-01-01

Web conferencing is a promising tool for online education. A well-developed teaching strategy can lead to effective use of this technology to create a sense of community, engage students, and promote academic integrity in online courses. This article presents strategies for integrating Web conferencing into online nursing courses.

78 FR 25277 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

...-related problems, obesity prevention has become a public health priority. Physical activity and dietary... physically active. Thus, one promising strategy to address nutrition and physical activity is through policy... improve nutrition and physical activity. CDC and others have recommended strategies to decrease sedentary...

Precision Therapy of Head and Neck Squamous Cell Carcinoma.

PubMed

Polverini, P J; D'Silva, N J; Lei, Y L

2018-06-01

Precision medicine is an approach to disease prevention and treatment that takes into account genetic variability and environmental and lifestyle influences that are unique to each patient. It facilitates stratification of patient populations that vary in their susceptibility to disease and response to therapy. Shared databases and the implementation of new technology systems designed to advance the integration of this information will enable health care providers to more accurately predict and customize prevention and treatment strategies for patients. Although precision medicine has had a limited impact in most areas of medicine, it has been shown to be an increasingly successful approach to cancer therapy. Despite early promising results targeting aberrant signaling pathways or inhibitors designed to block tumor-driven processes such as angiogenesis, limited success emphasizes the need to discover new biomarkers and treatment targets that are more reliable in predicting response to therapy and result in better health outcomes. Recent successes in the use of immunity-inducing antibodies have stimulated increased interest in the use of precision immunotherapy of head and neck squamous cell carcinoma. Using next-generation sequencing, the precise profiling of tumor-infiltrating lymphocytes has great promise to identify hypoimmunogenic cancer that would benefit from a rationally designed combinatorial approach. Continued interrogation of tumors will reveal new actionable targets with increasing therapeutic efficacy and fulfill the promise of precision therapy of head and neck cancer.

Electrical Stimulation of Afferent Pathways for the Suppression of Pathological Tremor

PubMed Central

Dideriksen, Jakob L.; Laine, Christopher M.; Dosen, Strahinja; Muceli, Silvia; Rocon, Eduardo; Pons, José L.; Benito-Leon, Julian; Farina, Dario

2017-01-01

Pathological tremors are involuntary oscillatory movements which cannot be fully attenuated using conventional treatments. For this reason, several studies have investigated the use of neuromuscular electrical stimulation for tremor suppression. In a recent study, however, we found that electrical stimulation below the motor threshold also suppressed tremor, indicating involvement of afferent pathways. In this study, we further explored this possibility by systematically investigating how tremor suppression by afferent stimulation depends on the stimulation settings. In this way, we aimed at identifying the optimal stimulation strategy, as well as to elucidate the underlying physiological mechanisms of tremor suppression. Stimulation strategies varying the stimulation intensity and pulse timing were tested in nine tremor patients using either intramuscular or surface stimulation. Significant tremor suppression was observed in six patients (tremor suppression > 75% was observed in three patients) and the average optimal suppression level observed across all subjects was 52%. The efficiency for each stimulation setting, however, varied substantially across patients and it was not possible to identify a single set of stimulation parameters that yielded positive results in all patients. For example, tremor suppression was achieved both with stimulation delivered in an out-of-phase pattern with respect to the tremor, and with random timing of the stimulation. Overall, these results indicate that low-current stimulation of afferent fibers is a promising approach for tremor suppression, but that further research is required to identify how the effect can be maximized in the individual patient. PMID:28420958

Identification of At-Risk Youth by Suicide Screening in a Pediatric Emergency Department.

PubMed

Ballard, Elizabeth D; Cwik, Mary; Van Eck, Kathryn; Goldstein, Mitchell; Alfes, Clarissa; Wilson, Mary Ellen; Virden, Jane M; Horowitz, Lisa M; Wilcox, Holly C

2017-02-01

The pediatric emergency department (ED) is a critical location for the identification of children and adolescents at risk for suicide. Screening instruments that can be easily incorporated into clinical practice in EDs to identify and intervene with patients at increased suicide risk is a promising suicide prevention strategy and patient safety objective. This study is a retrospective review of the implementation of a brief suicide screen for pediatric psychiatric ED patients as standard of care. The Ask Suicide Screening Questions (ASQ) was implemented in an urban pediatric ED for patients with psychiatric presenting complaints. Nursing compliance rates, identification of at-risk patients, and sensitivity for repeated ED visits were evaluated using medical records from 970 patients. The ASQ was implemented with a compliance rate of 79 %. Fifty-three percent of the patients who screened positive (237/448) did not present to the ED with suicide-related complaints. These identified patients were more likely to be male, African American, and have externalizing behavior diagnoses. The ASQ demonstrated a sensitivity of 93 % and specificity of 43 % to predict return ED visits with suicide-related presenting complaints within 6 months of the index visit. Brief suicide screening instruments can be incorporated into standard of care in pediatric ED settings. Such screens can identify patients who do not directly report suicide-related presenting complaints at triage and who may be at particular risk for future suicidal behavior. Results have the potential to inform suicide prevention strategies in pediatric EDs.

Microarray-assisted fine-mapping of quantitative trait loci for cold tolerance in rice.

PubMed

Liu, Fengxia; Xu, Wenying; Song, Qian; Tan, Lubin; Liu, Jiayong; Zhu, Zuofeng; Fu, Yongcai; Su, Zhen; Sun, Chuanqing

2013-05-01

Many important agronomic traits, including cold stress resistance, are complex and controlled by quantitative trait loci (QTLs). Isolation of these QTLs will greatly benefit the agricultural industry but it is a challenging task. This study explored an integrated strategy by combining microarray with QTL-mapping in order to identify cold-tolerant QTLs from a cold-tolerant variety IL112 at early-seedling stage. All the early seedlings of IL112 survived normally for 9 d at 4-5°C, while Guichao2 (GC2), an indica cultivar, died after 4 d under the same conditions. Using the F2:3 population derived from the progeny of GC2 and IL112, we identified seven QTLs for cold tolerance. Furthermore, we performed Affymetrix rice whole-genome array hybridization and obtained the expression profiles of IL112 and GC2 under both low-temperature and normal conditions. Four genes were selected as cold QTL-related candidates, based on microarray data mining and QTL-mapping. One candidate gene, LOC_Os07g22494, was shown to be highly associated with cold tolerance in a number of rice varieties and in the F2:3 population, and its overexpression transgenic rice plants displayed strong tolerance to low temperature at early-seedling stage. The results indicated that overexpression of this gene (LOC_Os07g22494) could increase cold tolerance in rice seedlings. Therefore, this study provides a promising strategy for identifying candidate genes in defined QTL regions.

Nudging consumers towards healthier choices: a systematic review of positional influences on food choice.

PubMed

Bucher, Tamara; Collins, Clare; Rollo, Megan E; McCaffrey, Tracy A; De Vlieger, Nienke; Van der Bend, Daphne; Truby, Helen; Perez-Cueto, Federico J A

2016-06-01

Nudging or 'choice architecture' refers to strategic changes in the environment that are anticipated to alter people's behaviour in a predictable way, without forbidding any options or significantly changing their economic incentives. Nudging strategies may be used to promote healthy eating behaviour. However, to date, the scientific evidence has not been systematically reviewed to enable practitioners and policymakers to implement, or argue for the implementation of, specific measures to support nudging strategies. This systematic review investigated the effect of positional changes of food placement on food choice. In total, seven scientific databases were searched using relevant keywords to identify interventions that manipulated food position (proximity or order) to generate a change in food selection, sales or consumption, among normal-weight or overweight individuals across any age group. From 2576 identified articles, fifteen articles comprising eighteen studies met our inclusion criteria. This review has identified that manipulation of food product order or proximity can influence food choice. Such approaches offer promise in terms of impacting on consumer behaviour. However, there is a need for high-quality studies that quantify the magnitude of positional effects on food choice in conjunction with measuring the impact on food intake, particularly in the longer term. Future studies should use outcome measures such as change in grams of food consumed or energy intake to quantify the impact on dietary intake and potential impacts on nutrition-related health. Research is also needed to evaluate potential compensatory behaviours secondary to such interventions.

Pre-K as School Turnaround Strategy

ERIC Educational Resources Information Center

Buenafe, Anthony Q.

2011-01-01

Both state and local school systems, recognizing the strong and growing evidence of pre-kindergarten's effectiveness in closing achievement gaps, are implementing early learning programs as part of their education reform efforts. In low-performing districts, pre-k has emerged as a promising turnaround strategy, reaching children before they become…

Policy, Systems, and Environmental Change in the Mississippi Delta: Considerations for Evaluation Design

ERIC Educational Resources Information Center

Kegler, Michelle C.; Honeycutt, Sally; Davis, Melvin; Dauria, Emily; Berg, Carla; Dove, Cassandra; Gamble, Abigail; Hawkins, Jackie

2015-01-01

Community-level policy, systems, and environmental (PSE) change strategies may offer an economical and sustainable approach to chronic disease prevention. The rapidly growing number of untested but promising PSE strategies currently underway offers an exciting opportunity to establish practice-based evidence for this approach. This article…

Strife and Progress: Portfolio Strategies for Managing Urban Schools

ERIC Educational Resources Information Center

Campbell, Christine; Gross, Betheny; Hill, Paul T.

2012-01-01

Deficient urban schooling remains one of America's most pressing--and stubborn--public policy problems. This important new book details and evaluates a radical and promising new approach to K-12 education reform. "Strife and Progress" explains for a broad audience the "portfolio strategy" for providing urban education--its…

Video Self-Modeling as an Intervention Strategy for Individuals with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Gelbar, Nicholas W.; Anderson, Candace; McCarthy, Scott; Buggey, Tom

2012-01-01

Video self-modeling demonstrates promise as an intervention strategy to improve outcomes in individuals with autism spectrum disorders. This article summarizes the empirical evidence supporting the use of video self-modeling with individuals with autism spectrum disorders to increase language and communication, increase social skills, modify…

Recruitment and Retention of Latino Children in a Lifestyle Intervention

ERIC Educational Resources Information Center

Guzman, Angelica; Richardson, Irma M.; Gesell, Sabina; Barkin, Shari L.

2009-01-01

Objective: To describe promising recruitment and retention strategies for transient Latino populations, assisting investigators who work with this population in their research design and implementation. Methods: Strategies in recruitment and retention from a year-long intervention in children and their families are described. Results: Of the 159…

Adaptive Treatment Strategies in Youth Mental Health: A Commentary on Advantages, Challenges, and Potential Directions.

PubMed

Sherrill, Joel T

2016-01-01

This commentary underscores the importance and potential of the research approaches and intervention strategies described in the JCCAP special issue on the Science of Adaptive Treatment Strategies in Child and Adolescent Mental Health for addressing the widely observed heterogeneity in response to even our most promising research-informed interventions. First, the commentary briefly summarizes the advantages of these approaches and highlights how these programs of research are responsive to widely agreed-upon calls for more personalized, prescriptive interventions. Next, the commentary briefly discusses key common challenges and gaps in our knowledge that might be addressed to advance the development, testing, and implementation of adaptive intervention strategies. For example, research to identify robust moderators that might serve as potential tailoring variables for initial assignment and sequencing of interventions, efforts to operationalize surrogate endpoints for early identification of individuals who are unlikely to respond to first-line interventions, and research that helps define what constitutes an adequate exposure (i.e., dose) or response threshold (e.g., response that suggests the need to intensify, switch, or augment interventions) would inform decision rules for adaptive algorithms. The commentary concludes with a discussion of potential strategies and current initiatives that might ultimately help facilitate research on more targeted, prescriptive approaches to intervening, including efforts to encourage investigators to use common data elements, to share and integrate data across trials, and to employ a more mechanism-based approach to intervention development and testing.

Therapeutic and prevention strategies against human enterovirus 71 infection

PubMed Central

Kok, Chee Choy

2015-01-01

Human enterovirus 71 (HEV71) is the cause of hand, foot and mouth disease and associated neurological complications in children under five years of age. There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade, and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved. PMID:25964873

Lighting and vegetation for energy-efficient and safe roadway travel : final report (1,015.15 KB)

DOT National Transportation Integrated Search

2009-05-01

The objective of the present study was to identify and evaluate promising approaches to incorporating : lighting and vegetation along roadways with the purpose of identifying the most promising application that : could be incorporated into a demonstr...

Deep-learning networks and the functional architecture of executive control.

PubMed

Cooper, Richard P

2017-01-01

Lake et al. underrate both the promise and the limitations of contemporary deep learning techniques. The promise lies in combining those techniques with broad multisensory training as experienced by infants and children. The limitations lie in the need for such systems to possess functional subsystems that generate, monitor, and switch goals and strategies in the absence of human intervention.

Recruiting Community Partners for Veggie Van: Strategies and Lessons Learned From a Mobile Market Intervention in North Carolina, 2012-2015.

PubMed

Tripicchio, Gina L; Grady Smith, Jacqueline; Armstrong-Brown, Janelle; McGuirt, Jared; Haynes-Maslow, Lindsey; Mardovich, Sarah; Ammerman, Alice S; Leone, Lucia

2017-04-27

Food access interventions are promising strategies for improving dietary intake, which is associated with better health. However, studies examining the relationship between food access and intake are limited to observational designs, indicating a need for more rigorous approaches. The Veggie Van (VV) program was a cluster-randomized intervention designed to address the gap between food access and intake. In this article, we aim to describe the approaches involved in recruiting community partners to participate in VV. The VV mobile market aimed to improve access to fresh fruits and vegetables by providing subsidized, high-quality, local produce in low-resource communities in North Carolina. This study describes the strategies and considerations involved in recruiting community partners and individual participants for participation in the VV program and evaluation. To recruit partners, we used various strategies, including a site screener to identify potential partners, interest forms to gauge future VV use and prioritize enrollment of a high-need population, marketing materials to promote VV, site liaisons to coordinate community outreach, and a memorandum of understanding between all invested parties. A total of 53 community organizations and 725 participants were approached for recruitment. Ultimately, 12 sites and 201 participants were enrolled. Enrollment took 38 months, but our approaches helped successfully recruit a low-income, low-access population. The process took longer than anticipated, and funding constraints prevented certain strategies from being implemented. Recruiting community partners and members for participation in a multi-level, community-based intervention was challenging. Strategies and lessons learned can inform future studies.

Turning great strategy into great performance.

PubMed

Mankins, Michael C; Steele, Richard

2005-01-01

Despite the enormous time and energy that goes into strategy development, many companies have little to show for their efforts. Indeed, research by the consultancy Marakon Associates suggests that companies on average deliver only 63% of the financial performance their strategies promise. In this article, Michael Mankins and Richard Steele of Marakon present the findings of this research. They draw on their experience with high-performing companies like Barclays, Cisco, Dow Chemical, 3M, and Roche to establish some basic rules for setting and delivering strategy: Keep it simple, make it concrete. Avoid long, drawn-out descriptions of lofty goals and instead stick to clear language describing what your company will and won't do. Debate assumptions, not forecasts. Create cross-functional teams drawn from strategy, marketing, and finance to ensure the assumptions underlying your long-term plans reflect both the real economics of your company's markets and its actual performance relative to competitors. Use a rigorous analytic framework. Ensure that the dialogue between the corporate center and the business units about market trends and assumptions is conducted within a rigorous framework, such as that of "profit pools". Discuss resource deployments early. Create more realistic forecasts and more executable plans by discussing up front the level and timing of critical deployments. Clearly identify priorities. Prioritize tactics so that employees have a clear sense of where to direct their efforts. Continuously monitor performance. Track resource deployment and results against plan, using continuous feedback to reset assumptions and reallocate resources. Reward and develop execution capabilities. Motivate and develop staff. Following these rules strictly can help narrow the strategy-to-performance gap.

Chemicals from Biomass: A Market Assessment of Bioproducts with Near-Term Potential

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

Biddy, Mary J.; Scarlata, Christopher; Kinchin, Christopher

Production of chemicals from biomass offers a promising opportunity to reduce U.S. dependence on imported oil, as well as to improve the overall economics and sustainability of an integrated biorefinery. Given the increasing momentum toward the deployment and scale-up of bioproducts, this report strives to: (1) summarize near-term potential opportunities for growth in biomass-derived products; (2) identify the production leaders who are actively scaling up these chemical production routes; (3) review the consumers and market champions who are supporting these efforts; (4) understand the key drivers and challenges to move biomass-derived chemicals to market; and (5) evaluate the impact thatmore » scale-up of chemical strategies will have on accelerating the production of biofuels.« less

[Targeted therapy: toward a clean and effective war against cancer].

PubMed

Castronovo, V; Waltregny, D; Detry, O; Coimbra Marques, C; De Roover, A; Honoré, P; De Pauw, E; Turtoi, A

2009-01-01

One promising avenue towards the development of more selective, better anticancer drugs consists in the targeted delivery of bioactive compounds to the tumor environment by means of binding molecules specific for tumor-associated biomarkers. Eligibility of such markers for therapeutic use implies ideally three criteria : (i) accessibility from the bloodstream, (ii) expression at sufficient level and (iii) no (or much lower) expression in normal tissues. Most current discovery strategies (such as biomarker searching into body fluids) provide no clue as to whether proteins of interest are accessible, in human tissues, to suitable high-affinity ligands, such as systemically delivered monoclonal antibodies. Innovative proteomic technologies are able to identify such accessible biomarkers and represent a key step in the clinical development of such target therapies.

miRNAs as therapeutic targets in ischemic heart disease.

PubMed

Frost, Robert J A; van Rooij, Eva

2010-06-01

Ischemic heart disease is a form of congestive heart failure that is caused by insufficient blood supply to the heart, resulting in a loss of viable tissue. In response to the injury, the non-ischemic myocardium displays signs of secondary remodeling, like interstitial fibrosis and hypertrophy of cardiac myocytes. This remodeling process further deteriorates pump function and increases susceptibility to arrhythmias. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression in a sequence-dependent manner. Recently, several groups identified miRNAs as crucial gene regulators in response to myocardial infarction (MI) and during post-MI remodeling. In this review, we discuss how modulation of these miRNAs represents a promising new therapeutic strategy to improve the clinical outcome in ischemic heart disease.

Comprehensive molecular tumor profiling in radiation oncology: How it could be used for precision medicine.

PubMed

Eke, Iris; Makinde, Adeola Y; Aryankalayil, Molykutty J; Ahmed, Mansoor M; Coleman, C Norman

2016-11-01

New technologies enabling the analysis of various molecules, including DNA, RNA, proteins and small metabolites, can aid in understanding the complex molecular processes in cancer cells. In particular, for the use of novel targeted therapeutics, elucidation of the mechanisms leading to cell death or survival is crucial to eliminate tumor resistance and optimize therapeutic efficacy. While some techniques, such as genomic analysis for identifying specific gene mutations or epigenetic testing of promoter methylation, are already in clinical use, other "omics-based" assays are still evolving. Here, we provide an overview of the current status of molecular profiling methods, including promising research strategies, as well as possible challenges, and their emerging role in radiation oncology. Published by Elsevier Ireland Ltd.

Encouraging consumption of water in school and child care settings: access, challenges, and strategies for improvement.

PubMed

Patel, Anisha I; Hampton, Karla E

2011-08-01

Children and adolescents are not consuming enough water, instead opting for sugar-sweetened beverages (sodas, sports and energy drinks, milks, coffees, and fruit-flavored drinks with added sugars), 100% fruit juice, and other beverages. Drinking sufficient amounts of water can lead to improved weight status, reduced dental caries, and improved cognition among children and adolescents. Because children spend most of their day at school and in child care, ensuring that safe, potable drinking water is available in these settings is a fundamental public health measure. We sought to identify challenges that limit access to drinking water; opportunities, including promising practices, to increase drinking water availability and consumption; and future research, policy efforts, and funding needed in this area.

Evolution of rational vaccine designs for genital herpes immunotherapy.

PubMed

Kaufmann, Johanna Katharina; Flechtner, Jessica Baker

2016-04-01

Immunotherapeutic vaccines have emerged as a novel treatment modality for genital herpes, a sexually transmitted disease mainly caused by herpes simplex virus type 2. The approaches to identify potential vaccine antigens have evolved from classic virus attenuation and characterization of antibody and T cell responses in exposed, but seronegative individuals, to systematic screens for novel T cell antigens. Combined with implementation of novel vaccine concepts revolving around immune evasion and local recruitment of immune effectors, the development of a safe and effective therapeutic vaccine is within reach. Here, we describe the vaccine approaches that currently show promise at clinical and pre-clinical stages and link them to the evolving scientific strategies that led to their identification. Copyright © 2016 Elsevier B.V. All rights reserved.

Targeting Cardiomyocyte Ca2+ Homeostasis in Heart Failure

PubMed Central

Røe, Åsmund T.; Frisk, Michael; Louch, William E.

2015-01-01

Improved treatments for heart failure patients will require the development of novel therapeutic strategies that target basal disease mechanisms. Disrupted cardiomyocyte Ca2+ homeostasis is recognized as a major contributor to the heart failure phenotype, as it plays a key role in systolic and diastolic dysfunction, arrhythmogenesis, and hypertrophy and apoptosis signaling. In this review, we outline existing knowledge of the involvement of Ca2+ homeostasis in these deficits, and identify four promising targets for therapeutic intervention: the sarcoplasmic reticulum Ca2+ ATPase, the Na+-Ca2+ exchanger, the ryanodine receptor, and t-tubule structure. We discuss experimental data indicating the applicability of these targets that has led to recent and ongoing clinical trials, and suggest future therapeutic approaches. PMID:25483944

Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis.

PubMed

Proitsi, Petroula; Kim, Min; Whiley, Luke; Simmons, Andrew; Sattlecker, Martina; Velayudhan, Latha; Lupton, Michelle K; Soininen, Hillka; Kloszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Powell, John F; Dobson, Richard J B; Legido-Quigley, Cristina

2017-02-01

The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex). We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods. We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R 2  = 0.10, test data set) and brain atrophy (R 2  ≥ 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines. Blood lipids are promising AD biomarkers that may lead to new treatment strategies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Computational fishing of new DNA methyltransferase inhibitors from natural products.

PubMed

Maldonado-Rojas, Wilson; Olivero-Verbel, Jesus; Marrero-Ponce, Yovani

2015-07-01

DNA methyltransferase inhibitors (DNMTis) have become an alternative for cancer therapies. However, only two DNMTis have been approved as anticancer drugs, although with some restrictions. Natural products (NPs) are a promising source of drugs. In order to find NPs with novel chemotypes as DNMTis, 47 compounds with known activity against these enzymes were used to build a LDA-based QSAR model for active/inactive molecules (93% accuracy) based on molecular descriptors. This classifier was employed to identify potential DNMTis on 800 NPs from NatProd Collection. 447 selected compounds were docked on two human DNA methyltransferase (DNMT) structures (PDB codes: 3SWR and 2QRV) using AutoDock Vina and Surflex-Dock, prioritizing according to their score values, contact patterns at 4 Å and molecular diversity. Six consensus NPs were identified as virtual hits against DNMTs, including 9,10-dihydro-12-hydroxygambogic, phloridzin, 2',4'-dihydroxychalcone 4'-glucoside, daunorubicin, pyrromycin and centaurein. This method is an innovative computational strategy for identifying DNMTis, useful in the identification of potent and selective anticancer drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

[Innovative care and self-care strategies for people with chronic diseases in Latin America].

PubMed

Sapag, Jaime C; Lange, Ilta; Campos, Solange; Piette, John D

2010-01-01

To identify innovative strategies for improved care and self-care of patients with chronic diseases (CD) in Latin America and to explore interest in creating a Latin American network of professionals in this field. A descriptive study based on a survey of key experts with recognized national or regional leadership in CD patient care. The 25-question questionnaire sought information on their experiences with care and self-care initiatives for CD patients, descriptions of successful initiatives, the perceived ability of countries to innovate in this area, their interest in participating in a network of Latin American professionals in this field, and more. Content analysis was performed to develop recommendations for the Region. Responses were obtained from 17 (37.8%) of the 45 experts approached; 82.4% confirmed their knowledge of of involvement with an innovative initiative related to the subject. Initial development does exist in each of the three innovative strategy types: peer care, informal caregivers, and telenursing, the latter being the least explored. There is real interest in forming a Latin American network that focuses on development of innovative self-care strategies for CD patients. Support for a joint network is promising. Priorities are building skills in this area and developing innovative proposals for improved CD patient care in the Region. Innovative measures should be complementary and adapted to the specific context of each scenario.

Limit, lean or listen? A typology of low-value care that gives direction in de-implementation.

PubMed

Verkerk, Eva W; Tanke, Marit A C; Kool, Rudolf B; van Dulmen, Simone A; Westert, Gert P

2018-05-07

Overuse of unnecessary care is widespread around the world. This so-called low-value care provides no benefit for the patient, wastes resources and can cause harm. The concept of low-value care is broad and there are different reasons for care to be of low-value. Hence, different strategies might be necessary to reduce it and awareness of this may help in designing a de-implementation strategy. Based on a literature scan and discussions with experts, we identified three types of low-value care. The type ineffective care is proven ineffective, such as antibiotics for a viral infection. Inefficient care is in essence effective, but is of low-value through inefficient provision or inappropriate intensity, such as chronic benzodiazepine use. Unwanted care is in essence appropriate for the clinical condition it targets, but is low-value since it does not fit the patients' preferences, such as a treatment aimed to cure a patient that prefers palliative care. In this paper, we argue that these three types differ in their most promising strategy for de-implementation and that our typology gives direction in choosing whether to limit, lean or listen. We developed a typology that provides insight in the different reasons for care to be of low-value. We believe that this typology is helpful in designing a tailor-made strategy for reducing low-value care.

Rationale and methods of discovering hormetins as drugs for healthy ageing.

PubMed

Rattan, Suresh I S

2012-05-01

Mild stress-induced hormesis is becoming increasingly attractive as an ageing interventional strategy and is leading to the discovery of hormesis-inducing compounds called hormetins. Almost 50 years of modern biogerontolgical research has established a clear framework regarding the biological basis of ageing and longevity, and it is now generally accepted that ageing occurs in spite of the presence of complex pathways of maintenance, repair and defense, and there is no 'enemy within.' This viewpoint makes modulation of ageing different from the treatment of one or more age-related diseases. A promising strategy to slow down ageing and prevent or delay the onset of age-related diseases is that of mild stress-induced hormesis by using hormetins. The article presents the rationale and a strategy for discovering novel hormetins as potential drugs for ageing intervention by elucidating multiple stress responses of normal human cells. Furthermore, it discusses the first steps in identifying prospective hormetin drugs and provides a recent example of successful product development, based on the ideas of hormesis and by following the strategy described here. As a biomedical issue, the biological process of ageing underlies several major diseases, and although the optimal treatment of every disease, irrespective of age, is a social and moral necessity, preventing the onset of age-related diseases by intervening in the basic process of ageing is the best approach for achieving healthy ageing and for extending the healthspan.

Emerging Trends in "Smart Probiotics": Functional Consideration for the Development of Novel Health and Industrial Applications.

PubMed

El Hage, Racha; Hernandez-Sanabria, Emma; Van de Wiele, Tom

2017-01-01

The link between gut microbiota and human health is well-recognized and described. This ultimate impact on the host has contributed to explain the mutual dependence between humans and their gut bacteria. Gut microbiota can be manipulated through passive or active strategies. The former includes diet, lifestyle, and environment, while the latter comprise antibiotics, pre- and probiotics. Historically, conventional probiotic strategies included a phylogenetically limited diversity of bacteria and some yeast strains. However, biotherapeutic strategies evolved in the last years with the advent of fecal microbiota transplant (FMT), successfully applied for treating CDI, IBD, and other diseases. Despite the positive outcomes, long-term effects resulting from the uncharacterized nature of FMT are not sufficiently studied. Thus, developing strategies to simulate the FMT, using characterized gut colonizers with identified phylogenetic diversity, may be a promising alternative. As the definition of probiotics states that the microorganism should have beneficial effects on the host, several bacterial species with proven efficacy have been considered next generation probiotics. Non-conventional candidate strains include Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis , and members of the Clostridia clusters IV, XIVa, and XVIII. However, viable intestinal delivery is one of the current challenges, due to their stringent survival conditions. In this review, we will cover current perspectives on the development and assessment of next generation probiotics and the approaches that industry and stakeholders must consider for a successful outcome.

Systematic review of knowledge, confidence and education in nutritional genomics for students and professionals in nutrition and dietetics.

PubMed

Wright, O R L

2014-06-01

This review examines knowledge and confidence of nutrition and dietetics professionals in nutritional genomics and evaluates the teaching strategies in this field within nutrition and dietetics university programmes and professional development courses internationally. A systematic search of 10 literature databases was conducted from January 2000 to December 2012 to identify original research. Any studies of either nutrition and/or dietetics students or dietitians/nutritionists investigating current levels of knowledge or confidence in nutritional genomics, or strategies to improve learning and/or confidence in this area, were eligible. Eighteen articles (15 separate studies) met the inclusion criteria. Three articles were assessed as negative, eight as neutral and seven as positive according to the American Dietetics Association Quality Criteria Checklist. The overall ranking of evidence was low. Dietitians have low involvement, knowledge and confidence in nutritional genomics, and evidence for educational strategies is limited and methodologically weak. There is a need to develop training pathways and material to up-skill nutrition and/or dietetics students and nutrition and/or dietetics professionals in nutritional genomics through multidisciplinary collaboration with content area experts. There is a paucity of high quality evidence on optimum teaching strategies; however, methods promoting repetitive exposure to nutritional genomics material, problem-solving, collaborative and case-based learning are most promising for university and professional development programmes. © 2013 The British Dietetic Association Ltd.

Diffusion and dissemination of evidence-based dietary srategies for the prevention of cancer

PubMed Central

Ciliska, Donna; Robinson, Paula; Armour, Tanya; Ellis, Peter; Brouwers, Melissa; Gauld, Mary; Baldassarre, Fulvia; Raina, Parminder

2005-01-01

Objective The purpose was to determine what strategies have been evaluated to disseminate cancer control interventions that promote the uptake of adult healthy diet? Methods A systematic review was conducted. Studies were identified by searching MEDLINE, PREMEDLINE, Cancer LIT, EMBASE/Excerpta Medica, PsycINFO, CINAHL, the Cochrane Database of Systematic Reviews, and reference lists and by contacting technical experts. English-language primary studies were selected if they evaluated the dissemination of healthy diet interventions in individuals, healthcare providers, or institutions. Studies of children or adolescents only were excluded. Results One hundred one articles were retrieved for full text screening. Nine reports of seven distinct studies were included; four were randomized trials, one was a cohort design and three were descriptive studies. Six studies were rated as methodologically weak, and one was rated as moderate. Studies were not meta-analyzed because of heterogeneity, low methodological quality, and incomplete data reporting. No beneficial dissemination strategies were found except one that looks promising, the use of peer educators in the worksite, which led to a short-term increase in fruit and vegetable intake. Conclusions and Implications Overall, the quality of the evidence is not strong and is primarily descriptive rather than evaluative. No clear conclusions can be drawn from these data. Controlled studies are needed to evaluate dissemination strategies, and to compare dissemination and diffusion strategies with different messages and different target audiences. PMID:15819991

A machine-learning approach for damage detection in aircraft structures using self-powered sensor data

NASA Astrophysics Data System (ADS)

Salehi, Hadi; Das, Saptarshi; Chakrabartty, Shantanu; Biswas, Subir; Burgueño, Rigoberto

2017-04-01

This study proposes a novel strategy for damage identification in aircraft structures. The strategy was evaluated based on the simulation of the binary data generated from self-powered wireless sensors employing a pulse switching architecture. The energy-aware pulse switching communication protocol uses single pulses instead of multi-bit packets for information delivery resulting in discrete binary data. A system employing this energy-efficient technology requires dealing with time-delayed binary data due to the management of power budgets for sensing and communication. This paper presents an intelligent machine-learning framework based on combination of the low-rank matrix decomposition and pattern recognition (PR) methods. Further, data fusion is employed as part of the machine-learning framework to take into account the effect of data time delay on its interpretation. Simulated time-delayed binary data from self-powered sensors was used to determine damage indicator variables. Performance and accuracy of the damage detection strategy was examined and tested for the case of an aircraft horizontal stabilizer. Damage states were simulated on a finite element model by reducing stiffness in a region of the stabilizer's skin. The proposed strategy shows satisfactory performance to identify the presence and location of the damage, even with noisy and incomplete data. It is concluded that PR is a promising machine-learning algorithm for damage detection for time-delayed binary data from novel self-powered wireless sensors.

Automatic Segmentation of Drosophila Neural Compartments Using GAL4 Expression Data Reveals Novel Visual Pathways.

PubMed

Panser, Karin; Tirian, Laszlo; Schulze, Florian; Villalba, Santiago; Jefferis, Gregory S X E; Bühler, Katja; Straw, Andrew D

2016-08-08

Identifying distinct anatomical structures within the brain and developing genetic tools to target them are fundamental steps for understanding brain function. We hypothesize that enhancer expression patterns can be used to automatically identify functional units such as neuropils and fiber tracts. We used two recent, genome-scale Drosophila GAL4 libraries and associated confocal image datasets to segment large brain regions into smaller subvolumes. Our results (available at https://strawlab.org/braincode) support this hypothesis because regions with well-known anatomy, namely the antennal lobes and central complex, were automatically segmented into familiar compartments. The basis for the structural assignment is clustering of voxels based on patterns of enhancer expression. These initial clusters are agglomerated to make hierarchical predictions of structure. We applied the algorithm to central brain regions receiving input from the optic lobes. Based on the automated segmentation and manual validation, we can identify and provide promising driver lines for 11 previously identified and 14 novel types of visual projection neurons and their associated optic glomeruli. The same strategy can be used in other brain regions and likely other species, including vertebrates. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Automatic identification approach for high-performance liquid chromatography-multiple reaction monitoring fatty acid global profiling.

PubMed

Tie, Cai; Hu, Ting; Jia, Zhi-Xin; Zhang, Jin-Lan

2015-08-18

Fatty acids (FAs) are a group of lipid molecules that are essential to organisms. As potential biomarkers for different diseases, FAs have attracted increasing attention from both biological researchers and the pharmaceutical industry. A sensitive and accurate method for globally profiling and identifying FAs is required for biomarker discovery. The high selectivity and sensitivity of high-performance liquid chromatography-multiple reaction monitoring (HPLC-MRM) gives it great potential to fulfill the need to identify FAs from complicated matrices. This paper developed a new approach for global FA profiling and identification for HPLC-MRM FA data mining. Mathematical models for identifying FAs were simulated using the isotope-induced retention time (RT) shift (IRS) and peak area ratios between parallel isotope peaks for a series of FA standards. The FA structures were predicated using another model based on the RT and molecular weight. Fully automated FA identification software was coded using the Qt platform based on these mathematical models. Different samples were used to verify the software. A high identification efficiency (greater than 75%) was observed when 96 FA species were identified in plasma. This FAs identification strategy promises to accelerate FA research and applications.

What Factors Influence the Decision to Share Suicidal Thoughts? A Multilevel Social Network Analysis of Disclosure Among Individuals with Serious Mental Illness.

PubMed

Fulginiti, Anthony; Pahwa, Rohini; Frey, Laura M; Rice, Eric; Brekke, John S

2016-08-01

Nondisclosure of suicidal thoughts limits suicide risk management. Consistent with disclosure models for other stigmatized statuses, understanding suicidal disclosure requires accounting for features of the discloser (individual factors) and the discloser-recipient relationship (relational factors). In a sample of 30 adults with schizophrenia, bipolar disorder, or major depressive disorder (Level 2) who nominated 436 social network members (Level 1), we examined disclosure patterns and identified individual and relational correlates of disclosure intent. Most individuals disclosed in the past (77%; n = 23) and all intended on disclosing (100%; n = 30). Disclosure was highly selective, with 14% (n = 62) of network members identified as prior confidants and 23% (n = 99) identified as intended confidants. Multilevel modeling indicated that relational factors were more central to disclosure than individual factors. Network members who were prior confidants and who provided social support were attractive targets for intended disclosure. Our findings suggest that "targeted" gatekeeper training may be a promising strategy and reveal relational characteristics to identify "high-probability confidants." © 2015 The American Association of Suicidology.

Protein Alterations in Infiltrating Ductal Carcinomas of the Breast as Detected by Nonequilibrium pH Gradient Electrophoresis and Mass Spectrometry

PubMed Central

Kabbage, Maria; Chahed, Karim; Hamrita, Bechr; Guillier, Christelle Lemaitre; Trimeche, Mounir; Remadi, Sami; Hoebeke, Johan; Chouchane, Lotfi

2008-01-01

Improvement of breast-cancer detection through the identification of potential cancer biomarkers is considered as a promising strategy for effective assessment of the disease. The current study has used nonequilibrium pH gradient electrophoresis with subsequent analysis by mass spectrometry to identify protein alterations in invasive ductal carcinomas of the breast from Tunisian women. We have identified multiple protein alterations in tumor tissues that were picked, processed, and unambiguously assigned identities by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF). The proteins identified span a wide range of functions and are believed to have potential clinical applications as cancer biomarkers. They include glycolytic enzymes, molecular chaperones, cytoskeletal-related proteins, antioxydant enzymes, and immunologic related proteins. Among these proteins, enolase 1, phosphoglycerate kinase 1, deoxyhemoglobin, Mn-superoxyde dismutase, α-B-crystallin, HSP27, Raf kinase inhibitor protein, heterogeneous nuclear ribonucleoprotein A2/B1, cofilin 1, and peptidylprolyl isomerase A were overexpressed in tumors compared with normal tissues. In contrast, the IGHG1 protein, the complement C3 component C3c, which are two newly identified protein markers, were downregulated in IDCA tissues. PMID:18401453

Effects of HBV Genetic Variability on RNAi Strategies

PubMed Central

Panjaworayan, Nattanan; Brown, Chris M.

2011-01-01

RNAi strategies present promising antiviral strategies against HBV. RNAi strategies require base pairing between short RNAi effectors and targets in the HBV pregenome or other RNAs. Natural variation in HBV genotypes, quasispecies variation, or mutations selected by the RNAi strategy could potentially make these strategies less effective. However, current and proposed antiviral strategies against HBV are being, or could be, designed to avoid this. This would involve simultaneous targeting of multiple regions of the genome, or regions in which variation or mutation is not tolerated. RNAi strategies against single genotypes or against variable regions of the genome would need to have significant other advantages to be part of robust therapies. PMID:21760994

Implementing Health Impact Assessment Programs in State Health Agencies: Lessons Learned From Pilot Programs, 2009-2011.

PubMed

Goff, Nancy; Wyss, Kerry; Wendel, Arthur; Jarris, Paul

2016-01-01

Health Impact Assessment (HIA) has emerged as a promising tool to integrate health considerations into decision making. The growth and success of HIA practice in the United States will be dependent on building the capacity of practitioners. This article seeks to identify the role of state health agencies (SHAs) in building capacity for conducting HIAs and the key components of initiatives that produced effective HIAs and HIA programs. The authors proposed to answer 3 research questions: (1) What can be the role of the SHA in HIA? (2) What are the characteristics of successful state HIA programs? and (3) What are some effective strategies for building capacity for HIA in SHAs and local health departments? The authors reviewed program reports from the ASTHO's pilot state health agencies (California, Minnesota, Oregon, and Wisconsin) that, between 2009 and 2011, created HIA programs to provide HIA training, conduct HIAs, and build practitioner networks. Program reports were examined for shared themes on the role of SHAs in a statewide HIA initiative, the characteristics of successful programs, and effective strategies for building capacity. Despite differences among the programs, many shared themes existed. These include stressing the importance of a basic, sustained infrastructure for HIA practice; leveraging existing programs and networks; and working in partnership with diverse stakeholders. SHAs can build capacity for HIA, and SHAs can both lead and support the completion of individual HIAs. States and territories interested in starting comprehensive statewide HIA initiatives could consider implementing the strategies identified by the pilot programs.

Backcasting to identify food waste prevention and mitigation opportunities for infant feeding in maternity services.

PubMed

Ryan-Fogarty, Yvonne; Becker, Genevieve; Moles, Richard; O'Regan, Bernadette

2017-03-01

Food waste in hospitals is of major concern for two reasons: one, healthcare needs to move toward preventative and demand led models for sustainability and two, food system sustainability needs to seek preventative measures such as diet adaptation and waste prevention. The impact of breast-milk substitute use on health services are well established in literature in terms of healthcare implications, cost and resourcing, however as a food demand and waste management issue little has been published to date. This paper presents the use of a desk based backcasting method to analyse food waste prevention, mitigation and management options within the Irish Maternity Service. Best practice in healthcare provision and waste management regulations are used to frame solutions. Strategic problem orientation revealed that 61% of the volume of ready to use breast-milk substitutes purchased by maternity services remains unconsumed and ends up as waste. Thirteen viable strategies to prevent and manage this waste were identified. Significant opportunities exist to prevent waste and also decrease food demand leading to both positive health and environmental outcomes. Backcasting methods display great promise in delivering food waste management strategies in healthcare settings, especially where evidenced best practice policies exist to inform solution forming processes. In terms of food waste prevention and management, difficulties arise in distinguishing between demand reduction, waste prevention and waste reduction measures under the current Waste Management Hierarchy definitions. Ultimately demand reduction at source requires prioritisation, a strategy which is complimentary to health policy on infant feeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

Employment and Self-Management: A Meta-Evaluation of Seven Literature Reviews

ERIC Educational Resources Information Center

Rusch, Frank R.; Dattilo, John

2012-01-01

Efforts focused on teaching individuals with intellectual disabilities to manage their own affairs have evolved over the past 30 years. Self-management strategies, in particular, hold much promise when the goal is to promote self-determination. In this article, the authors describe trends in the evolution of self-management strategies by analyzing…

Language Arts: Programming Suggestions for Hearing Impaired Students in Elementary Schools. Recommended Resources by the Alberta School for the Deaf.

ERIC Educational Resources Information Center

Alberta Dept. of Education, Edmonton.

The monograph is designed to assist program planning teams in developing language arts programs for hearing-impaired students in regular classrooms. Topics discussed include promising instructional strategies, description and evaluation of materials, and effective assessment instruments. The first section on instructional strategies covers…

Preparing Mathematics and Science Teachers for Diverse Classrooms: Promising Strategies for Transformative Pedagogy

ERIC Educational Resources Information Center

Rodriguez, Alberto J., Ed.; Kitchen, Richard S., Ed.

2005-01-01

This book provides a theoretical basis and practical strategies to counter resistance to learning to teach for diversity (in culturally and gender-inclusive ways), and resistance to teaching for understanding (using student-centered and inquiry-based pedagogical approaches). Teacher educators from across the United States present rich narratives…

City and State Takeover as a School Reform Strategy. ERIC Digest.

ERIC Educational Resources Information Center

Wong, Kenneth K.; Shen, Francis X.

This digest addresses city and state takeover as a school reform strategy, outlining the emergence of takeover in the past decade, discussing promises and limitations that takeover offers, and synthesizing the research to date on takeover's effectiveness. A notable trend over the past decade is greater implementation of takeover reforms,…

Synthetic Strategies to Terpene Quinones/Hydroquinones

PubMed Central

Gordaliza, Marina

2012-01-01

The cytotoxic and antiproliferative properties of many natural sesquiterpene-quinones and -hydroquinones from sponges offer promising opportunities for the development of new drugs. A review dealing with different strategies for obtaining bioactive terpenyl quinones/hydroquinones is presented. The different synthetic approches for the preparation of the most relevant quinones/hydroquinones are described. PMID:22412807

Ecological Contexts in the Development of Coalitions for Youth Violence Prevention: An Organizational Network Analysis

ERIC Educational Resources Information Center

Bess, Kimberly D.; Speer, Paul W.; Perkins, Douglas D.

2012-01-01

Community coalitions are a recognized strategy for addressing pressing public health problems. Despite the promise of coalitions as an effective prevention strategy, results linking coalition efforts to positive community outcomes are mixed. To date, research has primarily focused on determining organizational attributes related to successful…

Gamification Strategies in a Hybrid Exemplary College Course

ERIC Educational Resources Information Center

Machajewski, Szymon

2017-01-01

Using technology in teaching and learning finds a wide adoption in recent years. 63.3% of chief academic leaders surveyed by the Babson Survey Research Group confirm that online education is critical to their long-term strategy. Modern engagement pedagogies, such as digital gamification, hold a promise of shaping student experience. While course…

Observations on School District and Service Consolidation in Michigan. Working Paper #17

ERIC Educational Resources Information Center

Arsen, David

2011-01-01

School district consolidation enjoys a unique status among strategies to reduce education costs. It promises to cut spending, without lowering service quality, by improving the efficiency of service delivery. In contrast to strategies aimed at lowering employee salaries or benefits--which are hard to avoid when cutting spending in any labor…

Label-free electrochemical biosensing of small-molecule inhibition on O-GlcNAc glycosylation.

PubMed

Yang, Yu; Gu, Yuxin; Wan, Bin; Ren, Xiaomin; Guo, Liang-Hong

2017-09-15

O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) plays a critical role in modulating protein function in many cellular processes and human diseases such as Alzheimer's disease and type II diabetes, and has emerged as a promising new target. Specific inhibitors of OGT could be valuable tools to probe the biological functions of O-GlcNAcylation, but a lack of robust nonradiometric assay strategies to detect glycosylation, has impeded efforts to identify such compounds. Here we have developed a novel label-free electrochemical biosensor for the detection of peptide O-GlcNAcylation using protease-protection strategy and electrocatalytic oxidation of tyrosine mediated by osmium bipyridine as a signal reporter. There is a large difference in the abilities of proteolysis of the glycosylated and the unglycosylated peptides by protease, thus providing a sensing mechanism for OGT activity. When the O-GlcNAcylation is achieved, the glycosylated peptides cannot be cleaved by proteinase K and result in a high current response on indium tin oxide (ITO) electrode. However, when the O-GlcNAcylation is successfully inhibited using a small molecule, the unglycosylated peptides can be cleaved easily and lead to low current signal. Peptide O-GlcNAcylation reaction was performed in the presence of a well-defined small-molecule OGT inhibitor. The results indicated that the biosensor could be used to screen the OGT inhibitors effectively. Our label-free electrochemical method is a promising candidate for protein glycosylation pathway research in screening small-molecule inhibitors of OGT. Copyright © 2017 Elsevier B.V. All rights reserved.

Voxel-based automated detection of focal cortical dysplasia lesions using diffusion tensor imaging and T2-weighted MRI data.

PubMed

Wang, Yanming; Zhou, Yawen; Wang, Huijuan; Cui, Jin; Nguchu, Benedictor Alexander; Zhang, Xufei; Qiu, Bensheng; Wang, Xiaoxiao; Zhu, Mingwang

2018-05-21

The aim of this study was to automatically detect focal cortical dysplasia (FCD) lesions in patients with extratemporal lobe epilepsy by relying on diffusion tensor imaging (DTI) and T2-weighted magnetic resonance imaging (MRI) data. We implemented an automated classifier using voxel-based multimodal features to identify gray and white matter abnormalities of FCD in patient cohorts. In addition to the commonly used T2-weighted image intensity feature, DTI-based features were also utilized. A Gaussian processes for machine learning (GPML) classifier was tested on 12 patients with FCD (8 with histologically confirmed FCD) scanned at 1.5 T and cross-validated using a leave-one-out strategy. Moreover, we compared the multimodal GPML paradigm's performance with that of single modal GPML and classical support vector machine (SVM). Our results demonstrated that the GPML performance on DTI-based features (mean AUC = 0.63) matches with the GPML performance on T2-weighted image intensity feature (mean AUC = 0.64). More promisingly, GPML yielded significantly improved performance (mean AUC = 0.76) when applying DTI-based features to multimodal paradigm. Based on the results, it can also be clearly stated that the proposed GPML strategy performed better and is robust to unbalanced dataset contrary to SVM that performed poorly (AUC = 0.69). Therefore, the GPML paradigm using multimodal MRI data containing DTI modality has promising result towards detection of the FCD lesions and provides an effective direction for future researches. Copyright © 2018 Elsevier Inc. All rights reserved.

Anticancer Inhibitors of Hsp90 Function: Beyond the Usual Suspects

PubMed Central

Garg, Gaurav; Khandelwal, Anuj; Blagg, Brian S.J.

2018-01-01

The 90-kDa heat-shock protein (Hsp90) is a molecular chaperone responsible for the stability and function of a wide variety of client proteins that are critical for cell growth and survival. Many of these client proteins are frequently mutated and/or overexpressed in cancer cells and are therefore being actively pursued as individual therapeutic targets. Consequently, Hsp90 inhibition offers a promising strategy for simultaneous degradation of several anticancer targets. Currently, most Hsp90 inhibitors under clinical evaluation act by blocking the binding of ATP to the Hsp90 N-terminal domain and thereby, induce the degradation of many Hsp90-dependent oncoproteins. Although, they have shown some promising initial results, clinical challenges such as induction of the heat-shock response, retinopathy, and gastrointestinal tract toxicity are emerging from human trials, which constantly raise concerns about the future development of these inhibitors. Novobiocin derivatives, which do not bind the chaperone’s N-terminal ATPase pocket, have emerged over the past decade as an alternative strategy to inhibit Hsp90, but to date, no derivative has been investigated in the clinical setting. In recent years, a number of natural or synthetic compounds have been identified that modulate Hsp90 function via various mechanisms. These compounds not only offer new chemotypes for the development of future Hsp90 inhibitors but can also serve as chemical probes to unravel the biology of Hsp90. This chapter presents a synopsis of inhibitors that directly, allosterically, or even indirectly alters Hsp90 function, and highlights their proposed mechanisms of action. PMID:26916001

Interventions to Improve Neonatal Health and Later Survival: An Overview of Systematic Reviews.

PubMed

Lassi, Zohra S; Middleton, Philippa F; Crowther, Caroline; Bhutta, Zulfiqar A

2015-08-01

Evidence-based interventions and strategies are needed to improve child survival in countries with a high burden of neonatal and child mortality. An overview of systematic reviews can focus implementation on the most effective ways to increase child survival. In this overview we included published Cochrane and other systematic reviews of experimental and observational studies on antenatal, childbirth, postnatal and child health interventions aiming to prevent perinatal/neonatal and child mortality using the WHO list of essential interventions. We assessed the methodological quality of the reviews using the AMSTAR criteria and assessed the quality of the outcomes using the GRADE approach. Based on the findings from GRADE criteria, interventions were summarized as effective, promising or ineffective. The overview identified 148 Cochrane and other systematic reviews on 61 reproductive, maternal, newborn and child health interventions. Of these, only 57 reviews reported mortality outcomes. Using the GRADE approach, antenatal corticosteroids for preventing neonatal respiratory distress syndrome in preterm infants; early initiation of breastfeeding; hygienic cord care; kangaroo care for preterm infants; provision and promotion of use of insecticide treated bed nets (ITNs) for children; and vitamin A supplementation for infants from six months of age, were identified as clearly effective interventions for reducing neonatal, infant or child mortality. Antenatal care, tetanus immunization in pregnancy, prophylactic antimalarials during pregnancy, induction of labour for prolonged pregnancy, case management of neonatal sepsis, meningitis and pneumonia, prophylactic and therapeutic use of surfactant, continuous positive airway pressure for neonatal resuscitation, case management of childhood malaria and pneumonia, vitamin A as part of treatment for measles associated pneumonia for children above 6 months, and home visits across the continuum of care, were identified as promising interventions for reducing neonatal, infant, child or perinatal mortality. Comprehensive adoption of the above six effective and 11 promising interventions can improve neonatal and child survival around the world. Choice of intervention and degree of implementation currently depends on resources available and policies in individual countries and geographical settings. This review was part of doctoral thesis which was funded by University of Adelaide, Australia.

Innovative care models for high-cost Medicare beneficiaries: delivery system and payment reform to accelerate adoption.

PubMed

Davis, Karen; Buttorff, Christine; Leff, Bruce; Samus, Quincy M; Szanton, Sarah; Wolff, Jennifer L; Bandeali, Farhan

2015-05-01

About a third of Medicare beneficiaries are covered by Medicare Advantage (MA) plans or accountable care organizations (ACOs). As a result of assuming financial risk for Medicare services and/or being eligible for shared savings, these organizations have an incentive to adopt models of delivering care that contribute to better care, improved health outcomes, and lower cost. This paper identifies innovative care models across the care continuum for high-cost Medicare beneficiaries that MA plans and ACOs could adopt to improve care while potentially achieving savings. It suggests policy changes that would accelerate testing and spread of promising care delivery model innovations. Targeted review of the literature to identify care delivery models focused on high-cost or high-risk Medicare beneficiaries. This paper presents select delivery models for high-risk Medicare beneficiaries across the care continuum that show promise of yielding better care at lower cost that could be considered for adoption by MA plans and ACOs. Common to these models are elements of the Wagner Chronic Care Model, including practice redesign to incorporate a team approach to care, the inclusion of nonmedical personnel, efforts to promote patient engagement, supporting provider education on innovations,and information systems allowing feedback of information to providers. The goal of these models is to slow the progression to long-term care, reduce health risks, and minimize adverse health impacts, all while achieving savings.These models attempt to maintain the ability of high-risk individuals to live in the home or a community-based setting, thereby avoiding costly institutional care. Identifying and implementing promising care delivery models will become increasingly important in launching successful population health initiatives. MA plans and ACOs stand to benefit financially from adopting care delivery models for high-risk Medicare beneficiaries that reduce hospitalization. Spreading these models to other organizations will require provider payment policy changes. Integration of acute and long-term care would further spur adoption of effective strategies for reducing or delaying entry into long-term institutional care.

Association analysis for disease resistance to Fusarium oxysporum in cape gooseberry (Physalis peruviana L).

PubMed

Osorio-Guarín, Jaime A; Enciso-Rodríguez, Felix E; González, Carolina; Fernández-Pozo, Noé; Mueller, Lukas A; Barrero, Luz Stella

2016-03-18

Vascular wilt caused by Fusarium oxysporum is the most important disease in cape gooseberry (Physalis peruviana L.) in Colombia. The development of resistant cultivars is considered one of the most cost-effective means to reduce the impact of this disease. In order to do so, it is necessary to provide breeders with molecular markers and promising germplasm for introgression of different resistance loci as part of breeding schemes. Here we described an association mapping study in cape gooseberry with the goal to: (i) select promising materials for use in plant breeding and (ii) identify SNPs associated with the cape gooseberry resistance response to the F. oxysporum pathogen under greenhouse conditions, as potential markers for cape gooseberry breeding. We found a total of 21 accessions with different resistance responses within a diversity panel of 100 cape gooseberry accessions. A total of 60,663 SNPs were also identified within the same panel by means of GBS (Genotyping By Sequencing). Model-based population structure and neighbor-joining analyses showed three populations comprising the cape gooseberry panel. After correction for population structure and kinship, we identified SNPs markers associated with the resistance response against F. oxysporum. The identification of markers was based on common tags using the reference genomes of tomato and potato as well as the root/stem transcriptome of cape gooseberry. By comparing their location with the tomato genome, 16 SNPs were found in genes involved in defense/resistance response to pathogens, likewise when compared with the genome of potato, 12 markers were related. The work presented herein provides the first association mapping study in cape gooseberry showing both the identification of promising accessions with resistance response phenotypes and the identification of a set of SNP markers mapped to defense/resistance response genes of reference genomes. Thus, the work also provides new knowledge on candidate genes involved in the P. peruviana - F. oxysporum pathosystem as a foundation for further validation in marker-assisted selection. The results have important implications for conservation and breeding strategies in cape gooseberry.

Melanoma Vaccines: Mixed Past, Promising Future

PubMed Central

Ozao-Choy, Junko; Lee, Delphine J.; Faries, Mark B.

2014-01-01

Synopsis Cancer vaccines were one of the earliest forms of immunotherapy to be investigated. Past attempts to vaccinate against cancer, including melanoma, have mixed results, revealing the complexity of what was thought to be a simple concept. However, several recent successes and the combination of improved knowledge of tumor immunology and the advent of new immunomodulators make vaccination a promising strategy for the future. PMID:25245965

Task Force Report 4. Report of the Task Force on Marketing and Communications

PubMed Central

Dickinson, John C.; Evans, Kenneth L.; Carter, Jan; Burke, Kevin

2004-01-01

BACKGROUND To ensure the success of the proposed New Model of family medicine and to create a better understanding of the nature and role of family medicine, an effective communications plan must be developed and implemented. This Future of Family Medicine task force report proposes strategies for communicating the role of family physicians within medicine, as well as to purchasers, consumers, and other entities. METHODS After reviewing the findings from the research conducted for the Future of Family Medicine project, the task force presents a preliminary brand-positioning strategy for family medicine messages. Based on this strategy, the task force identifies 5 major audiences to which family medicine communications should be directed. A consistent method was used to determine optimum strategies to address each audience: defining the audience, assessing the literature and other pertinent evidence, identifying the communication objectives, determining the key messages, developing brand promises, and proposing strategies and tactics to support the messages and objectives. Preliminary communications plans are then presented for each of the 5 target audiences. MAJOR FINDINGS It is important that the organizations involved in family medicine make a multiyear commitment of resources to implement and support an aggressive communications strategy, which is based on key messages to target audiences. A concerted effort is particularly needed to address the declining interest among medical students in the specialty. Implementing a comprehensive family medicine career development program may be one effective strategy to reverse this trend. To help eliminate the current confusion among the public regarding family medicine and to promote clarity and consistency in terminology, the specialty should replace the name family practice with family medicine and a new graphic symbol for the discipline of family medicine should be developed. CONCLUSION As a discipline, family medicine has failed to formulate and deliver a compelling message. New communications strategies must be implemented that will reach audiences in terms they understand and care about and in ways that convey a sense of the exciting role family physicians will play in the future. By actively implementing the communications plans described in this report, the specialty can enhance the impact and help ensure the widespread implementation of the proposed New Model of family medicine.

Expeditionary Force Health Protection for Global Health Engagement: Lessons Learned from Continuing Promise 2017.

PubMed

Johnson, Lucas A; Lennon, Robert P

2018-05-01

Global health engagement (GHE) is an important priority for the Military Health Service as such activities strengthen the health capabilities of partner nations and improve interoperability. By their very nature, GHE activities are predominantly conducted in low-resource areas with limited infrastructure and substantial humanitarian need. The Department of Defense is evaluating leaner, flexible force packages to accomplish GHE missions and better prepare uniformed medical providers to provide care in austere environments. Observations made during the execution of Continuing Promise 2017, a recurring civil-military humanitarian operation conducted in Central and South America, are offered herein. Descriptions of relevant force health protection (FHP) threats experienced by mission personnel and mitigation measures successfully employed to prevent illness are provided. Relevant Department of Defense instructions are reviewed and risk mitigation strategies are compared with published standards and expert recommendations. In addition to well-described sanitation, hygiene, and infectious disease challenges that traditionally accompany military field activities, providing health care services to host nation populations in low-resource settings generates unique FHP vulnerabilities. Public health expertise leveraged throughout the planning and execution of GHE activities is instrumental for successfully identifying and mitigating the numerous FHP risks present. Experiences from Continuing Promise 2017 demonstrate the expeditionary public health practitioner's role as a force multiplier has never been more relevant. A variety of public health countermeasures are available to successfully mitigate FHP threats experienced during GHE events. The public health lessons learned from Continuing Promise 2017 assist mission planners, commanders, and health care providers ensure that GHE participants remain healthy enough to accomplish the mission and meet America's commitments to partner nations.

American Grand Strategy: The End of Primacy?

DTIC Science & Technology

2015-02-13

play internationally. Historian Walter McDougall describes this enduring debate as one between adherents to the vision of the country as either...our values by making the United States something worth emulating.23 This debate continues today; McDougall aptly notes that “while America the...2010,8. 20 Noonan, “America’s Strategy Deficit,” 1. 21 Drezner, “Does Obama Have a Grand Strategy?”, 3. 22 McDougall , Promised Land, Crusader State

Encoded novel forms of HSP70 or a cytolytic protein increase DNA vaccine potency.

PubMed

Garrod, Tamsin; Grubor-Bauk, Branka; Yu, Stanley; Gargett, Tessa; Gowans, Eric J

2014-01-01

In humans, DNA vaccines have failed to demonstrate the equivalent levels of immunogenicity that were shown in smaller animals. Previous studies have encoded adjuvants, predominantly cytokines, within these vaccines in an attempt to increase antigen-specific immune responses. However, these strategies have lacked breadth of innate immune activation and have led to disappointing results in clinical trials. Damage associated molecular patterns (DAMPs) have been identified as pattern recognition receptor (PRR) agonists. DAMPs can bind to a wide range of PRRs on dendritic cells (DCs) and thus our studies have aimed to utilize this characteristic to act as an adjuvant in a DNA vaccine approach. Specifically, HSP70 has been identified as a DAMP, but has been limited by its lack of accessibility to PRRs in and on DCs. Here, we discuss the promising results achieved with the inclusion of membrane-bound or secreted HSP70 into a DNA vaccine encoding HIV gag as the model immunogen.

I PLAY AT WORK—ten principles for transforming work processes through gamification

PubMed Central

Oprescu, Florin; Jones, Christian; Katsikitis, Mary

2014-01-01

Gamified workplaces could be a positive and innovative solution to addressing contemporary problems in organizations. Such problems include high levels of stress, reduced sense of community, reduced loyalty and rapid changes in the workforce. To better prepare organizations for the future it may be helpful to identify and understand the potential advantages, disadvantages and areas for future research in relationship to the use of gamification for personal and organizational wellbeing. An analysis of research literature across disciplines in combination with expert opinion identified gamified workplaces as a promising strategy for promoting wellbeing. Furthermore, this paper proposes a set of 10 principles (I PLAY AT WORK) that may support gamification efforts. In addition to the value of mapping the present for the benefit of the future, there is also considerable value in reshaping core ideas related to the workplaces. Gamified workplaces can provide opportunities for a more vigorous and strategic inter-disciplinary research agenda that can stimulate investments in the area. PMID:24523704

Value propositions of mHealth projects.

PubMed

Gorski, Irena; Bram, Joshua T; Sutermaster, Staci; Eckman, Molly; Mehta, Khanjan

While mHealth holds great potential for addressing global health disparities, a majority of the initiatives never proceed beyond the pilot stage. One fundamental concern is that mHealth projects are seldom designed from the customer's perspective to address their specific problems and/or create appreciable value. A customer-centric view, where direct tangible benefits of interventions are identified and communicated effectively, can drive customer engagement and advance projects toward self-sustaining business models. This article reviews the business models of 234 mHealth projects to identify nine distinct value propositions that solve specific problems for customers. Each of these value propositions is discussed with real-world examples, analyses of their design approaches and business strategies, and common enablers as well as hurdles to surviving past the pilot stage. Furthermore, a deeper analysis of 42 mHealth ventures that have achieved self-sustainability through project revenue provides a host of practical and poignant insights into the design of systems that can fulfil mHealth's promise to address healthcare challenges in the long term.

A Whole Cell Pathway Screen Reveals Seven Novel Chemosensitizers to Combat Chloroquine Resistant Malaria

PubMed Central

Ch'ng, Jun-Hong; Mok, Sachel; Bozdech, Zbynek; Lear, Martin James; Boudhar, Aicha; Russell, Bruce; Nosten, Francois; Tan, Kevin Shyong-Wei

2013-01-01

Due to the widespread prevalence of resistant parasites, chloroquine (CQ) was removed from front-line antimalarial chemotherapy in the 1990s despite its initial promise of disease eradication. Since then, resistance-conferring mutations have been identified in transporters such as the PfCRT, that allow for the efflux of CQ from its primary site of action, the parasite digestive vacuole. Chemosensitizing/chemoreversing compounds interfere with the function of these transporters thereby sensitizing parasites to CQ once again. However, compounds identified thus far have disappointing in vivo efficacy and screening for alternative candidates is required to revive this strategy. In this study, we propose a simple and direct means to rapidly screen for such compounds using a fluorescent-tagged CQ molecule. When this screen was applied to a small library, seven novel chemosensitizers (octoclothepin, methiothepin, metergoline, loperamide, chlorprothixene, L-703,606 and mibefradil) were quickly elucidated, including two which showed greater potency than the classical chemosensitizers verapamil and desipramine. PMID:23615863

Effect of N-Terminal Acylation on the Activity of Myostatin Inhibitory Peptides.

PubMed

Takayama, Kentaro; Nakamura, Akari; Rentier, Cédric; Mino, Yusaku; Asari, Tomo; Saga, Yusuke; Taguchi, Akihiro; Yakushiji, Fumika; Hayashi, Yoshio

2016-04-19

Inhibition of myostatin, which negatively regulates skeletal muscle growth, is a promising strategy for the treatment of muscle atrophic disorders, such as muscular dystrophy, cachexia and sarcopenia. Recently, we identified peptide A (H-WRQNTRYSRIEAIKIQILSKLRL-NH2 ), the 23-amino-acid minimum myostatin inhibitory peptide derived from mouse myostatin prodomain, and highlighted the importance of its N-terminal tryptophan residue for the effective inhibition. In this study, we synthesized a series of acylated peptide derivatives focused on the tryptophan residue to develop potent myostatin inhibitors. As a result of the investigation, a more potent derivative of peptide A was successfully identified in which the N-terminal tryptophan residue is replaced with a 2-naphthyloxyacetyl moiety to give an inhibitory peptide three times (1.19±0.11 μm) more potent than parent peptide A (3.53±0.25 μm). This peptide could prove useful as a new starting point for the development of improved inhibitory peptides. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Making healthy behaviors the easy choice for employees: a review of the literature on environmental and policy changes in worksite health promotion.

PubMed

Kahn-Marshall, Jennifer L; Gallant, Mary P

2012-12-01

As employers look for ways to reduce rising health care costs, worksite health promotion interventions are increasingly being used to improve employee health behaviors. An alternative approach to traditional worksite health promotion programs is the implementation of environmental and/or policy changes to encourage employees to adopt healthier behaviors. This review examines the evidence for the effectiveness of worksite health promotion programs using environmental and/or policy changes either alone or in combination with individually focused health behavior change strategies. A review of the relevant literature, published between 1995 and 2010, identified 27 studies that met all inclusion criteria. Limited evidence was found for the effectiveness of environmental and/or policy changes alone (n = 11) to change employee behavior, but more promising results were identified with multicomponent interventions (n = 16). There is a strong need for improvement in the design and evaluation of future health promotion programs focusing solely on environmental and/or policy changes at the worksite.

Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production.

PubMed

George, Kevin W; Chen, Amy; Jain, Aakriti; Batth, Tanveer S; Baidoo, Edward E K; Wang, George; Adams, Paul D; Petzold, Christopher J; Keasling, Jay D; Lee, Taek Soon

2014-08-01

The ability to rapidly assess and optimize heterologous pathway function is critical for effective metabolic engineering. Here, we develop a systematic approach to pathway analysis based on correlations between targeted proteins and metabolites and apply it to the microbial production of isopentenol, a promising biofuel. Starting with a seven-gene pathway, we performed a correlation analysis to reduce pathway complexity and identified two pathway proteins as the primary determinants of efficient isopentenol production. Aided by the targeted quantification of relevant pathway intermediates, we constructed and subsequently validated a conceptual model of isopentenol pathway function. Informed by our analysis, we assembled a strain which produced isopentenol at a titer 1.5 g/L, or 46% of theoretical yield. Our engineering approach allowed us to accurately identify bottlenecks and determine appropriate pathway balance. Paired with high-throughput cloning techniques and analytics, this strategy should prove useful for the analysis and optimization of increasingly complex heterologous pathways. © 2014 Wiley Periodicals, Inc.

Complementary DNA display selection of high-affinity peptides binding the vacuolating toxin (VacA) of Helicobacter pylori.

PubMed

Hayakawa, Yumiko; Matsuno, Mitsuhiro; Tanaka, Makoto; Wada, Akihiro; Kitamura, Koichiro; Takei, Osamu; Sasaki, Ryuzo; Mizukami, Tamio; Hasegawa, Makoto

2015-09-01

Artificial peptides designed for molecular recognition of a bacterial toxin have been developed. Vacuolating cytotoxin A protein (VacA) is a major virulence factor of Helicobacter pylori, a gram-negative microaerophilic bacterium inhabiting the upper gastrointestinal tract, particularly the stomach. This study attempted to identify specific peptide sequences with high affinity for VacA using systematic directed evolution in vitro, a cDNA display method. A surface plasmon resonance-based biosensor and fluorescence correlation spectroscopy to examine binding of peptides with VacA identified a peptide (GRVNQRL) with high affinity. Cyclization of the peptide by attaching cysteine residues to both termini improved its binding affinity to VacA, with a dissociation constant (Kd ) of 58 nm. This study describes a new strategy for the development of artificial functional peptides, which are promising materials in biochemical analyses and medical applications. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

Life Course Typology of Adults Who Experienced Sexual Violence

PubMed Central

Draucker, Claire Burke; Martsolf, Donna S.

2011-01-01

Two qualitative methodologies were used to develop a life course typology of individuals who had been exposed to sexual violence. Interview narratives of 121 adult women and men who participated in qualitative study of women’s and men’s responses to sexual violence provided the data. The authors combined a narrative approach (holistic-content and holistic-form analysis) to describe the life courses of the participants and a qualitative person-oriented approach (cross-case analysis) to identify meaningful sub-groups within the total sample. The six groups are: (a) life of turmoil, (b) life of struggles, (c) diminished life, (d) taking control of life, (e), finding peace in life, and (f) getting life back to normal. This work exemplifies a promising strategy for identifying sub-groups of violence-exposed individuals within a heterogeneous sample. Such a typology could aid the development of treatment approaches that consider both the substance and the structure of an individual’s life course, rather than target one specific type of violence. PMID:19762554

I PLAY AT WORK-ten principles for transforming work processes through gamification.

PubMed

Oprescu, Florin; Jones, Christian; Katsikitis, Mary

2014-01-01

Gamified workplaces could be a positive and innovative solution to addressing contemporary problems in organizations. Such problems include high levels of stress, reduced sense of community, reduced loyalty and rapid changes in the workforce. To better prepare organizations for the future it may be helpful to identify and understand the potential advantages, disadvantages and areas for future research in relationship to the use of gamification for personal and organizational wellbeing. An analysis of research literature across disciplines in combination with expert opinion identified gamified workplaces as a promising strategy for promoting wellbeing. Furthermore, this paper proposes a set of 10 principles (I PLAY AT WORK) that may support gamification efforts. In addition to the value of mapping the present for the benefit of the future, there is also considerable value in reshaping core ideas related to the workplaces. Gamified workplaces can provide opportunities for a more vigorous and strategic inter-disciplinary research agenda that can stimulate investments in the area.

Blood biomarkers of kidney transplant rejection, an endless search?

PubMed

Jacquemont, Lola; Soulillou, Jean-Paul; Degauque, Nicolas

2017-07-01

The tailoring of immunosuppressive treatment is recognized as a promising strategy to improve long-term kidney graft outcome. To guide the standard care of transplant recipients, physicians need objective biomarkers that can identify an ongoing pathology with the graft or low intensity signals that will be later evolved to accelerated transplant rejection. The early identification of 'high-risk /low-risk' patients enables the adjustment of standard of caring, including managing the frequency of clinical visits and the immunosuppression dosing. Given their ease of availability and the compatibility with a large technical array, blood-based biomarkers have been widely scrutinized for use as potential predictive and diagnostic biomarkers. Areas covered: Here, the authors report on non-invasive biomarkers, such as modification of immune cell subsets and mRNA and miRNA profiles, identified in the blood of kidney transplant recipients collected before or after transplantation. Expert commentary: Combined with functional tests, the identification of biomarkers will improve our understanding of pathological processes and will contribute to a global improvement in clinical management.

A relational leadership perspective on unit-level safety climate.

PubMed

Thompson, Debra N; Hoffman, Leslie A; Sereika, Susan M; Lorenz, Holly L; Wolf, Gail A; Burns, Helen K; Minnier, Tamra E; Ramanujam, Rangaraj

2011-11-01

This study compared nursing staff perceptions of safety climate in clinical units characterized by high and low ratings of leader-member exchange (LMX) and explored characteristics that might account for differences. Frontline nursing leaders' actions are critical to ensure patient safety. Specific leadership behaviors to achieve this goal are underexamined. The LMX perspective has shown promise in nonhealthcare settings as a means to explain safety climate perceptions. Cross-sectional survey of staff (n = 711) and unit directors from 34 inpatient units in an academic medical center was conducted. Significant differences were found between high and low LMX scoring units on supervisor safety expectations, organizational learning-continuous improvement, total communication, feedback and communication about errors, and nonpunitive response to errors. The LMX perspective can be used to identify differences in perceptions of safety climate among nursing staff. Future studies are needed to identify strategies to improve staff safety attitudes and behaviors. Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

Engineering of carboligase activity reaction in Candida glabrata for acetoin production.

PubMed

Li, Shubo; Xu, Nan; Liu, Liming; Chen, Jian

2014-03-01

Utilization of Candida glabrata overproducing pyruvate is a promising strategy for high-level acetoin production. Based on the known regulatory and metabolic information, acetaldehyde and thiamine were fed to identify the key nodes of carboligase activity reaction (CAR) pathway and provide a direction for engineering C. glabrata. Accordingly, alcohol dehydrogenase, acetaldehyde dehydrogenase, pyruvate decarboxylase, and butanediol dehydrogenase were selected to be manipulated for strengthening the CAR pathway. Following the rational metabolic engineering, the engineered strain exhibited increased acetoin biosynthesis (2.24 g/L). In addition, through in silico simulation and redox balance analysis, NADH was identified as the key factor restricting higher acetoin production. Correspondingly, after introduction of NADH oxidase, the final acetoin production was further increased to 7.33 g/L. By combining the rational metabolic engineering and cofactor engineering, the acetoin-producing C. glabrata was improved stepwise, opening a novel pathway for rational development of microorganisms for bioproduction. Copyright © 2013. Published by Elsevier Inc.

Life-course typology of adults who experienced sexual violence.

PubMed

Draucker, Claire; Martsolf, Donna

2010-07-01

Two qualitative methodologies were used to develop a life-course typology of individuals who had been exposed to sexual violence. Interview narratives of 121 adult women and men who participated in qualitative study of women's and men's responses to sexual violence provided the data. The authors combined a narrative approach (holistic-content and holistic-form analysis) to describe the life courses of the participants and a qualitative person-oriented approach (cross-case analysis) to identify meaningful subgroups within the total sample. The six groups are as follows: (a) life of turmoil, (b) life of struggles, (c) diminished life, (d) taking control of life, (e), finding peace in life, and (f) getting life back to normal. This work exemplifies a promising strategy for identifying subgroups of violence-exposed individuals within a heterogeneous sample. Such a typology could aid the development of treatment approaches that consider both the substance and the structure of an individual's life course, rather than target one specific type of violence.

Identification of differentially expressed genes in response to mercury I and II stress in Trichoderma harzianum.

PubMed

Puglisi, Ivana; Faedda, Roberto; Sanzaro, Vincenzo; Lo Piero, Angela R; Petrone, Goffredo; Cacciola, Santa O

2012-09-15

Filamentous fungi are very promising organisms in both the control and the reduction of the amount of heavy metal released by human and industrial activities. In particular, Trichoderma harzianum demonstrated to be tolerant towards different heavy metals, such as mercury and cadmium, even though the mechanism underlying this tolerance is not fully understood. By using a particular strategy of the suppression subtractive hybridization technique, we were able to identify in the strain IMI 393899 of T. harzianum eight different genes up-regulated in the presence of mercury II with respect to cadmium. Among the genes identified, a possible role in the tolerance mechanism could be envisaged for hydrophobin, due to its ability to dissolve hydrophobic molecules into aqueous media. We also show that IMI 393899 grows at the same rate of control culture in the presence of mercury I and that all eight genes isolated were also up-regulated in this condition. Copyright © 2012 Elsevier B.V. All rights reserved.

Biomarkers for Psychiatry: The Journey from Fantasy to Fact, a Report of the 2013 CINP Think Tank

PubMed Central

Millan, Mark J.; Bahn, Sabine; Bertolino, Alessandro; Turck, Christoph W.; Kapur, Shitij; Möller, Hans-Jürgen; Dean, Brian

2015-01-01

Background: A think tank sponsored by the Collegium Internationale Neuropsychopharmacologium (CINP) debated the status and prospects of biological markers for psychiatric disorders, focusing on schizophrenia and major depressive disorder. Methods: Discussions covered markers defining and predicting specific disorders or domains of dysfunction, as well as predicting and monitoring medication efficacy. Deliberations included clinically useful and viable biomarkers, why suitable markers are not available, and the need for tightly-controlled sample collection. Results: Different types of biomarkers, appropriate sensitivity, specificity, and broad-based exploitability were discussed. Whilst a number of candidates are in the discovery phases, all will require replication in larger, real-life cohorts. Clinical cost-effectiveness also needs to be established. Conclusions: Since a single measure is unlikely to suffice, multi-modal strategies look more promising, although they bring greater technical and implementation complexities. Identifying reproducible, robust biomarkers will probably require pre-competitive consortia to provide the resources needed to identify, validate, and develop the relevant clinical tests. PMID:25899066

Systems approach to the pharmacological actions of HDAC inhibitors reveals EP300 activities and convergent mechanisms of regulation in diabetes.

PubMed

Rafehi, Haloom; Kaspi, Antony; Ziemann, Mark; Okabe, Jun; Karagiannis, Tom C; El-Osta, Assam

2017-01-01

Given the skyrocketing costs to develop new drugs, repositioning of approved drugs, such as histone deacetylase (HDAC) inhibitors, may be a promising strategy to develop novel therapies. However, a gap exists in the understanding and advancement of these agents to meaningful translation for which new indications may emerge. To address this, we performed systems-level analyses of 33 independent HDAC inhibitor microarray studies. Based on network analysis, we identified enrichment for pathways implicated in metabolic syndrome and diabetes (insulin receptor signaling, lipid metabolism, immunity and trafficking). Integration with ENCODE ChIP-seq datasets identified suppression of EP300 target genes implicated in diabetes. Experimental validation indicates reversal of diabetes-associated EP300 target genes in primary vascular endothelial cells derived from a diabetic individual following inhibition of HDACs (by SAHA), EP300, or EP300 knockdown. Our computational systems biology approach provides an adaptable framework for the prediction of novel therapeutics for existing disease.

Community assessment of availability, consumption, and cultural acceptability of food sources of (pro)vitamin A: toward the development of a dietary intervention among preschool children in rural Burkina Faso.

PubMed

Nana, Constance P; Brouwer, Inge D; Zagré, Noel-Marie; Kok, Frans J; Traoré, Alfred S

2005-12-01

Vitamin A deficiency remains a public health problem in Burkina Faso and elsewhere in the developing world. Dietary diversification is a promising strategy that needs to be explored to strengthen the country's ongoing supplementation program. The purpose of this study was to identify locally available and acceptable (pro)vitamin A-rich foods to be included in a dietary intervention addressing vitamin A deficiency in children aged six months to three years. A food ethnographic study combining recall methods, observation, and focused group discussion was conducted in the dry and rainy seasons. Thirty-five mother-child pairs were randomly selected and included in the study. The dietary pattern of children was characterized by low diversity with extremely low energy and vitamin A intake in both seasons. The study identified the availability of numerous (pro)vitamin A-rich foods, but these foods are either not consumed or consumed by few in low amounts and/or in low frequencies. The main constraining factors identified are related to financial accessibility (for liver), seasonal availability (for egg, milk, mango, papaya, and green leafy vegetables), and beliefs related to consumption and preparation (for green leafy vegetables). However, the study also revealed that the study population associated all identified (pro)vitamin A-rich foods with positive attributes such as health, strength, and vitamin richness, which might offer an entry point for designing and implementing dietary interventions. Based on the findings of this formative research, intervention strategies with mango and liver are proposed to improve the vitamin A intake and status of children in the rural areas of Burkina Faso.

Factors influencing primary health care professionals' physical activity promotion behaviors: a systematic review.

PubMed

Huijg, Johanna M; Gebhardt, Winifred A; Verheijden, Marieke W; van der Zouwe, Nicolette; de Vries, Juriena D; Middelkoop, Barend J C; Crone, Mathilde R

2015-02-01

Despite the promising findings related to the efficacy of interventions aimed at promoting physical activity (PA) in primary health care (PHC), the translation of these interventions to PHC practice does not always happen as desired. To help understand why efficacious PHC-based PA interventions are not effectively translated to practice, this study systematically reviewed the literature on factors influencing PHC professionals' PA promotion practices. Literature searches were conducted in Web of Science, PubMed, and PsycINFO for peer-reviewed articles published in English from 1990 onwards. Studies were included that met the following criteria: (1) involving PHC-based PA interventions, and (2) reporting factors influencing PHC professionals' PA promotion behaviors. Two researchers independently screened studies and extracted data. A narrative synthesis using thematic analysis was conducted to identify factors. Of the 4,469 identified articles, 59 were included in the review. Factors were identified by qualitative methods, barrier/facilitator ratings, and the examination of the relationship between factors and PA promotion, and the effectiveness of introduction strategies. Many factors related to the development, delivery, and effects of the innovation, the sociopolitical and organizational culture, resources, and support, patient and PHC professional characteristics, and innovation strategies were identified as potential influences on PHC professionals' PA promotion practices. However, the lack of evidence on the relationship between factors and PA promotion indicated insufficient evidence on PA promotion determinants. This extensive overview of potential factors can inform intervention developers and implementers on which factors may play a role when introducing PA interventions in PHC. Future research should further investigate relationships between factors and PA promotion, which should be guided by qualitative in-depth knowledge on influencing factors.

Torching the Haystack: modelling fast-fail strategies in drug development.

PubMed

Lendrem, Dennis W; Lendrem, B Clare

2013-04-01

By quickly clearing the development pipeline of failing or marginal products, fast-fail strategies release resources to focus on more promising molecules. The Quick-Kill model of drug development demonstrates that fast-fail strategies will: (1) reduce the expected time to market; (2) reduce expected R&D costs; and (3) increase R&D productivity. This paper outlines the model and demonstrates the impact of fast-fail strategies. The model is illustrated with costs and risks data from pharmaceutical and biopharmaceutical companies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Kinematic amplification strategies in plants and engineering

NASA Astrophysics Data System (ADS)

Charpentier, Victor; Hannequart, Philippe; Adriaenssens, Sigrid; Baverel, Olivier; Viglino, Emmanuel; Eisenman, Sasha

2017-06-01

While plants are primarily sessile at the organismal level, they do exhibit a vast array of movements at the organ or sub-organ level. These movements can occur for reasons as diverse as seed dispersal, nutrition, protection or pollination. Their advanced mechanisms generate a myriad of movement typologies, many of which are not fully understood. In recent years, there has been a renewal of interest in understanding the mechanical behavior of plants from an engineering perspective, with an interest in developing novel applications by up-sizing these mechanisms from the micro- to the macro-scale. This literature review identifies the main strategies used by plants to create and amplify movements and anatomize the most recent mechanical understanding of compliant engineering mechanics. The paper ultimately demonstrates that plant movements, rooted in compliance and multi-functionality, can effectively inspire better kinematic/adaptive structures and materials. In plants, the actuators and the deployment structures are fused into a single system. The understanding of those natural movements therefore starts with an exploration of mechanisms at the origins of movements. Plant movements, whether slow or fast, active or passive, reversible or irreversible, are presented and detailed for their mechanical significance. With a focus on displacement amplification, the most recent promising strategies for actuation and adaptive systems are examined with respect to the mechanical principles of shape morphing plant tissues.

Drug Repositioning for Effective Prostate Cancer Treatment.

PubMed

Turanli, Beste; Grøtli, Morten; Boren, Jan; Nielsen, Jens; Uhlen, Mathias; Arga, Kazim Y; Mardinoglu, Adil

2018-01-01

Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-κB inhibition, Wnt/β-Catenin pathway inhibition, DNMT1 inhibition, and GSK-3β inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.

Challenges and opportunities in suicide prevention in South-East Asia.

PubMed

Vijayakumar, Lakshmi

2017-04-01

Suicide is a global public health problem, with over 800 000 people worldwide dying by suicide in 2012, according to the World Health Organization (WHO). The WHO South-East Asia Region is especially affected, with 39% of global suicides occurring in the 11 countries in this region. Women are a particularly vulnerable population, for a variety of social and cultural reasons. In India specifically, deaths by suicide for women peak in the age range 15-29 years. There is sufficient evidence to show that reduction of easy access to means of suicide is an effective prevention strategy. A common method of suicide in the region is by ingestion of pesticides. Strategies that have targeted limiting access to pesticides as a means of preventing suicide, such as the use of central storage and locked boxes, have shown promising results. Given the limited human and economic resources in these countries, it is essential to involve all stakeholders, including health services, voluntary and community organizations, teachers, social workers, traditional healers and other gatekeepers, in suicide prevention. A multisectoral approach, specifically targeting women and reducing easy access to pesticides, should be the way forward to reducing suicides in this region. In addition, more research is needed, to identify cost-effective and sustainable strategies.

General Strategy for the Synthesis of Transition-Metal Phosphide/N-Doped Carbon Frameworks for Hydrogen and Oxygen Evolution.

PubMed

Pu, Zonghua; Zhang, Chengtian; Amiinu, Ibrahim Saana; Li, Wenqiang; Wu, Lin; Mu, Shichun

2017-05-17

Transition metal phosphides (TMPs) have been identified as promising nonprecious metal electrocatalyst for hydrogen evolution reaction (HER) and other energy conversion reactions. Herein, we reported a general strategy for synthesis of a series of TMPs (Fe 2 P, FeP, Co 2 P, CoP, Ni 2 P, and Ni 12 P 5 ) nanoparticles (NPs) with different metal phases embedded in a N-doped carbon (NC) matrix using metal salt, ammonium dihydrogen phosphate, and melamine as precursor with varying molar ratios and thermolysis temperatures. The resultant TMPs can serve as highly active and durable bifunctional electrocatalyst toward HER and oxygen evolution reaction (OER). In particular, the Ni 2 P@NC phase only requires an overpotential of ∼138 mV to derive HER in 0.5 M H 2 SO 4, and ∼320 mV for OER in 1.0 M KOH at the current density of 10 mA cm -2 . Because of the encapsulation of NC that can effectively prevent corrosion of embedded TMP NPs, Ni 2 P@NC exhibits almost unfading catalytic performance even after 10 h under both acidic and alkaline solutions. This synthesis strategy provides a new avenue to exploring TMPs as highly active and stable electrocatalyst for the HER, OER, and other electrochemical applications.

System Integration - A Major Step toward Lab on a Chip

PubMed Central

2011-01-01

Microfluidics holds great promise to revolutionize various areas of biological engineering, such as single cell analysis, environmental monitoring, regenerative medicine, and point-of-care diagnostics. Despite the fact that intensive efforts have been devoted into the field in the past decades, microfluidics has not yet been adopted widely. It is increasingly realized that an effective system integration strategy that is low cost and broadly applicable to various biological engineering situations is required to fully realize the potential of microfluidics. In this article, we review several promising system integration approaches for microfluidics and discuss their advantages, limitations, and applications. Future advancements of these microfluidic strategies will lead toward translational lab-on-a-chip systems for a wide spectrum of biological engineering applications. PMID:21612614

Efficient synthetic methods for the installation of boron-nitrogen bonds in conjugated organic molecules.

PubMed

Morgan, Matthew M; Piers, Warren E

2016-04-14

Polycyclic aromatic hydrocarbons in which one or more CC units have been replaced by isoelectronic BN units have attracted interest as potentially improved organic materials in various devices. This promise has been hampered by a lack of access to gram quantities of these materials. However, the exploitation of keystone reactions such as ring closing metathesis, borylative cyclization of amino styrenes and electrophilic borylation has lead to strategies for access to workable amounts of material. These strategies can be augmented by judicious postfunctionalization reactions to diversify the library of materials available. This Frontier article highlights some of the recent successes and shows that the long promised applications of BN-doped PAHs are beginning to be explored in a meaningful way.

Major depressive disorder: insight into candidate cerebrospinal fluid protein biomarkers from proteomics studies.

PubMed

Al Shweiki, Mhd Rami; Oeckl, Patrick; Steinacker, Petra; Hengerer, Bastian; Schönfeldt-Lecuona, Carlos; Otto, Markus

2017-06-01

Major Depressive Disorder (MDD) is the leading cause of global disability, and an increasing body of literature suggests different cerebrospinal fluid (CSF) proteins as biomarkers of MDD. The aim of this review is to summarize the suggested CSF biomarkers and to analyze the MDD proteomics studies of CSF and brain tissues for promising biomarker candidates. Areas covered: The review includes the human studies found by a PubMed search using the following terms: 'depression cerebrospinal fluid biomarker', 'major depression biomarker CSF', 'depression CSF biomarker', 'proteomics depression', 'proteomics biomarkers in depression', 'proteomics CSF biomarker in depression', and 'major depressive disorder CSF'. The literature analysis highlights promising biomarker candidates and demonstrates conflicting results on others. It reveals 42 differentially regulated proteins in MDD that were identified in more than one proteomics study. It discusses the diagnostic potential of the biomarker candidates and their association with the suggested pathologies. Expert commentary: One ultimate goal of finding biomarkers for MDD is to improve the diagnostic accuracy to achieve better treatment outcomes; due to the heterogeneous nature of MDD, using bio-signatures could be a good strategy to differentiate MDD from other neuropsychiatric disorders. Notably, further validation studies of the suggested biomarkers are still needed.

Potential benefits of superconductivity to transportation in the United States

NASA Astrophysics Data System (ADS)

Rote, Donald M.; Johnson, Larry R.

Research in U.S. transportation applications of superconductors is strongly motivated by a number of potential national benefits. These include the reduction of dependence on petroleum-based fuels, energy savings, substantially reduced air and noise pollution, increased customer convenience, and reduced maintenance costs. Current transportation technology offers little flexibility to switch to alternative fuels, and efforts to achieve the other benefits are confounded by growing congestion at airports and on urban roadways. A program has been undertaken to identify possible applications of the emerging superconducting applications to transportation and to evaluate potential national benefits. The current phase of the program will select the most promising applications for a more detailed subsequent study. Transportation modes being examined include highway and industrial vehicles, as well as rail, sea, air transport and pipelines. Three strategies are being considered: (1) replacing present components with those employing superconductors, (2) substituting new combinations of components or systems for present systems, and (3) developing completely new technologies. Distinctions are made between low-, medium-, and near-room-temperature superconductors. The most promising applications include magnetically levitated passenger and freight vehicles; replacement of drive systems in locomotives, self-propelled rail cars, and ships; and electric vehicles inductively coupled to electrified roadways.

Aerospace Technology Innovation. Volume 10

NASA Technical Reports Server (NTRS)

Turner, Janelle (Editor); Cousins, Liz (Editor); Bennett, Evonne (Editor); Vendette, Joel (Editor); West, Kenyon (Editor)

2002-01-01

Whether finding new applications for existing NASA technologies or developing unique marketing strategies to demonstrate them, NASA's offices are committed to identifying unique partnering opportunities. Through their efforts NASA leverages resources through joint research and development, and gains new insight into the core areas relevant to all NASA field centers. One of the most satisfying aspects of my job comes when I learn of a mission-driven technology that can be spun-off to touch the lives of everyday people. NASA's New Partnerships in Medical Diagnostic Imaging is one such initiative. Not only does it promise to provide greater dividends for the country's investment in aerospace research, but also to enhance the American quality of life. This issue of Innovation highlights the new NASA-sponsored initiative in medical imaging. Early in 2001, NASA announced the launch of the New Partnerships in Medical Diagnostic Imaging initiative to promote the partnership and commercialization of NASA technologies in the medical imaging industry. NASA and the medical imaging industry share a number of crosscutting technologies in areas such as high-performance detectors and image-processing tools. Many of the opportunities for joint development and technology transfer to the medical imaging market also hold the promise for future spin back to NASA.

A note on the efficiencies of sampling strategies in two-stage Bayesian regional fine mapping of a quantitative trait.

PubMed

Chen, Zhijian; Craiu, Radu V; Bull, Shelley B

2014-11-01

In focused studies designed to follow up associations detected in a genome-wide association study (GWAS), investigators can proceed to fine-map a genomic region by targeted sequencing or dense genotyping of all variants in the region, aiming to identify a functional sequence variant. For the analysis of a quantitative trait, we consider a Bayesian approach to fine-mapping study design that incorporates stratification according to a promising GWAS tag SNP in the same region. Improved cost-efficiency can be achieved when the fine-mapping phase incorporates a two-stage design, with identification of a smaller set of more promising variants in a subsample taken in stage 1, followed by their evaluation in an independent stage 2 subsample. To avoid the potential negative impact of genetic model misspecification on inference we incorporate genetic model selection based on posterior probabilities for each competing model. Our simulation study shows that, compared to simple random sampling that ignores genetic information from GWAS, tag-SNP-based stratified sample allocation methods reduce the number of variants continuing to stage 2 and are more likely to promote the functional sequence variant into confirmation studies. © 2014 WILEY PERIODICALS, INC.

PIM kinases as therapeutic targets against advanced melanoma

PubMed Central

Shannan, Batool; Watters, Andrea; Chen, Quan; Mollin, Stefan; Dörr, Markus; Meggers, Eric; Xu, Xiaowei; Gimotty, Phyllis A.; Perego, Michela; Li, Ling; Benci, Joseph; Krepler, Clemens; Brafford, Patricia; Zhang, Jie; Wei, Zhi; Zhang, Gao; Liu, Qin; Yin, Xiangfan; Nathanson, Katherine L.; Herlyn, Meenhard; Vultur, Adina

2016-01-01

Therapeutic strategies for the treatment of metastatic melanoma show encouraging results in the clinic; however, not all patients respond equally and tumor resistance still poses a challenge. To identify novel therapeutic targets for melanoma, we screened a panel of structurally diverse organometallic inhibitors against human-derived normal and melanoma cells. We observed that a compound that targets PIM kinases (a family of Ser/Thr kinases) preferentially inhibited melanoma cell proliferation, invasion, and viability in adherent and three-dimensional (3D) melanoma models. Assessment of tumor tissue from melanoma patients showed that PIM kinases are expressed in pre- and post-treatment tumors, suggesting PIM kinases as promising targets in the clinic. Using knockdown studies, we showed that PIM1 contributes to melanoma cell proliferation and tumor growth in vivo; however, the presence of PIM2 and PIM3 could also influence the outcome. The inhibition of all PIM isoforms using SGI-1776 (a clinically-available PIM inhibitor) reduced melanoma proliferation and survival in preclinical models of melanoma. This was potentiated in the presence of the BRAF inhibitor PLX4720 and in the presence of PI3K inhibitors. Our findings suggest that PIM inhibitors provide promising additions to the targeted therapies available to melanoma patients. PMID:27448973

Advances in the treatment of polyarticular juvenile idiopathic arthritis

PubMed Central

Webb, Kate; Wedderburn, Lucy R.

2015-01-01

Purpose of review To review recent advances in the management strategies of polyarticular course juvenile idiopathic arthritis (JIA) and identify unanswered questions and avenues for further research. Recent findings There is evidence for an early, aggressive, treat-to-target approach for polyarticular JIA. Clinical disease activity criteria have been recently defined and validated, including criteria for inactive disease and the juvenile arthritis disease activity score (JADAS). There is a need for evidence-based, defined disease targets and biomarkers for prediction of response, including targets for remission induction, and guidelines on drug withdrawal. Recent treatment consensus plans and guidelines are discussed and compared, including the 2015 NHS England clinical policy statement, the 2014 Childhood Arthritis and Rheumatology Research Alliance (CARRA) treatment plans and the 2011 American College of Rheumatology (ACR) guidelines. Evidence for new agents such as tocilizumab, rituximab, golimumab, ustekinumab, certolizumab and tofacitinib is promising: the recent clinical trials are summarized here. Stratification of individual patient treatment remains a goal, and predictive biomarkers have been shown to predict success in the withdrawal of methotrexate therapy. Summary There are promising advances in the treatment approaches, disease activity criteria, clinical guidelines, pharmaceutical choices and individually stratified therapy choices for polyarticular JIA. PMID:26147756

Population Pharmacokinetics and Optimal Sampling Strategy for Model-Based Precision Dosing of Melphalan in Patients Undergoing Hematopoietic Stem Cell Transplantation.

PubMed

Mizuno, Kana; Dong, Min; Fukuda, Tsuyoshi; Chandra, Sharat; Mehta, Parinda A; McConnell, Scott; Anaissie, Elias J; Vinks, Alexander A

2018-05-01

High-dose melphalan is an important component of conditioning regimens for patients undergoing hematopoietic stem cell transplantation. The current dosing strategy based on body surface area results in a high incidence of oral mucositis and gastrointestinal and liver toxicity. Pharmacokinetically guided dosing will individualize exposure and help minimize overexposure-related toxicity. The purpose of this study was to develop a population pharmacokinetic model and optimal sampling strategy. A population pharmacokinetic model was developed with NONMEM using 98 observations collected from 15 adult patients given the standard dose of 140 or 200 mg/m 2 by intravenous infusion. The determinant-optimal sampling strategy was explored with PopED software. Individual area under the curve estimates were generated by Bayesian estimation using full and the proposed sparse sampling data. The predictive performance of the optimal sampling strategy was evaluated based on bias and precision estimates. The feasibility of the optimal sampling strategy was tested using pharmacokinetic data from five pediatric patients. A two-compartment model best described the data. The final model included body weight and creatinine clearance as predictors of clearance. The determinant-optimal sampling strategies (and windows) were identified at 0.08 (0.08-0.19), 0.61 (0.33-0.90), 2.0 (1.3-2.7), and 4.0 (3.6-4.0) h post-infusion. An excellent correlation was observed between area under the curve estimates obtained with the full and the proposed four-sample strategy (R 2  = 0.98; p < 0.01) with a mean bias of -2.2% and precision of 9.4%. A similar relationship was observed in children (R 2  = 0.99; p < 0.01). The developed pharmacokinetic model-based sparse sampling strategy promises to achieve the target area under the curve as part of precision dosing.