Sample records for identify promising strategies

  1. CDC's DELTA FOCUS Program: Identifying Promising Primary Prevention Strategies for Intimate Partner Violence.

    PubMed

    Armstead, Theresa L; Rambo, Kirsten; Kearns, Megan; Jones, Kathryn M; Dills, Jenny; Brown, Pamela

    2017-01-01

    According to 2011 data, nearly one in four women and one in seven men in the United States experience severe physical violence by an intimate partner, creating a public health burden requiring population-level solutions. To prevent intimate partner violence (IPV) before it occurs, the CDC developed Domestic Violence Prevention Enhancements and Leadership Through Alliances, Focusing on Outcomes for Communities United with States to identify promising community- and societal-level prevention strategies to prevent IPV. The program funds 10 state domestic violence coalitions for 5 years to implement and evaluate programs and policies to prevent IPV by influencing the environments and conditions in which people live, work, and play. The program evaluation goals are to promote IPV prevention by identifying promising prevention strategies and describing those strategies using case studies, thereby creating a foundation for building practice-based evidence with a health equity approach.

  2. Maternity care and liability: least promising policy strategies for improvement.

    PubMed

    Sakala, Carol; Yang, Y Tony; Corry, Maureen P

    2013-01-01

    The present liability system is not serving well childbearing women and newborns, maternity care clinicians, or those who pay for maternity care. Examination of evidence about the impact of this system on maternity care led us to identify seven aims for a high-functioning liability system in this clinical context. Herein, we identify policy strategies that are unlikely to meet the proposed criteria and contribute to needed improvements. A companion paper considers more promising strategies. We considered whether 25 strategies that have been used or proposed for improvement have met or could meet the seven aims. We used a best available evidence approach and drew on more recent empirical legal studies and health services research about maternity care and liability, when available, and considered other studies when unavailable. Fifteen strategies seem to have little potential to improve liability matters in maternity care. Despite support for capping non-economic damages, a series of studies has found a modest impact at best on maternity care. Maternity-specific studies also do not lend support to tort reforms collectively and several other specific tort reforms. Some tort alternative and liability insurance reform strategies have narrow aims and are not policy priorities. Caps on non-economic damages and other tort reforms have narrow aims and have been marginally effective at best in the context of maternity care. Several other possible reforms similarly are not promising. Continued focus on these strategies is unlikely to result in the high-performing liability system that maternity care stakeholders need. Copyright © 2013 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  3. 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…

  4. Using the integrative model of behavioral prediction to identify promising message strategies to promote healthy sleep behavior among college students.

    PubMed

    Robbins, Rebecca; Niederdeppe, Jeff

    2015-01-01

    This research used the Integrative Model of Behavioral Prediction (IMBP) to examine cognitive predictors of intentions to engage in healthy sleep behavior among a population of college students. In doing so, we identify promising message strategies to increase healthy sleep behavior during college. In Phase 1, members of a small sample of undergraduates (n = 31) were asked to describe their beliefs about expected outcomes, norms, and perceived behavioral control associated with sleep on an open-ended questionnaire. We analyzed these qualitative responses to create a closed-ended survey about sleep-related attitudes, perceived norms, control beliefs, behavioral intentions, and behavior. In Phase 2, a larger sample of undergraduate students (n = 365) completed the survey. Attitudes and perceived behavioral control were the strongest predictors of both intentions to engage in sleep behavior and self-reported sleep behavior. Control beliefs associated with time management and stress also had substantial room to change, suggesting their potential as message strategies to better promote healthy sleep behavior in college. We conclude with a broader discussion of the study's implications for message design and intervention.

  5. Promising intervention strategies to reduce parents' use of physical punishment.

    PubMed

    Gershoff, Elizabeth T; Lee, Shawna J; Durrant, Joan E

    2017-09-01

    The strong and ever-growing evidence base demonstrating that physical punishment places children at risk for a range of negative outcomes, coupled with global recognition of children's inherent rights to protection and dignity, has led to the emergence of programs specifically designed to prevent physical punishment by parents. This paper describes promising programs and strategies designed for each of three levels of intervention - indicated, selective, and universal - and summarizes the existing evidence base of each. Areas for further program development and evaluation are identified. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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.

  7. 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.

  8. Strategies to design clinical studies to identify predictive biomarkers in cancer research.

    PubMed

    Perez-Gracia, Jose Luis; Sanmamed, Miguel F; Bosch, Ana; Patiño-Garcia, Ana; Schalper, Kurt A; Segura, Victor; Bellmunt, Joaquim; Tabernero, Josep; Sweeney, Christopher J; Choueiri, Toni K; Martín, Miguel; Fusco, Juan Pablo; Rodriguez-Ruiz, Maria Esperanza; Calvo, Alfonso; Prior, Celia; Paz-Ares, Luis; Pio, Ruben; Gonzalez-Billalabeitia, Enrique; Gonzalez Hernandez, Alvaro; Páez, David; Piulats, Jose María; Gurpide, Alfonso; Andueza, Mapi; de Velasco, Guillermo; Pazo, Roberto; Grande, Enrique; Nicolas, Pilar; Abad-Santos, Francisco; Garcia-Donas, Jesus; Castellano, Daniel; Pajares, María J; Suarez, Cristina; Colomer, Ramon; Montuenga, Luis M; Melero, Ignacio

    2017-02-01

    The discovery of reliable biomarkers to predict efficacy and toxicity of anticancer drugs remains one of the key challenges in cancer research. Despite its relevance, no efficient study designs to identify promising candidate biomarkers have been established. This has led to the proliferation of a myriad of exploratory studies using dissimilar strategies, most of which fail to identify any promising targets and are seldom validated. The lack of a proper methodology also determines that many anti-cancer drugs are developed below their potential, due to failure to identify predictive biomarkers. While some drugs will be systematically administered to many patients who will not benefit from them, leading to unnecessary toxicities and costs, others will never reach registration due to our inability to identify the specific patient population in which they are active. Despite these drawbacks, a limited number of outstanding predictive biomarkers have been successfully identified and validated, and have changed the standard practice of oncology. In this manuscript, a multidisciplinary panel reviews how those key biomarkers were identified and, based on those experiences, proposes a methodological framework-the DESIGN guidelines-to standardize the clinical design of biomarker identification studies and to develop future research in this pivotal field. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. 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.

  10. Solutions for Failing High Schools: Converging Visions and Promising Models.

    ERIC Educational Resources Information Center

    Legters, Nettie; Balfanz, Robert; McPartland, James

    Promising solutions to the failings of traditional comprehensive high schools were reviewed to identify basic principles and strategies for improving high schools nationwide. Selected research studies, policy documents, and promising high school programs were reviewed. The review revealed the following principles for helping high schools better…

  11. 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…

  12. 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...

  13. Candida Biofilms: Threats, Challenges, and Promising Strategies.

    PubMed

    Cavalheiro, Mafalda; Teixeira, Miguel Cacho

    2018-01-01

    Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis , and Candida parapsilosis , highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.

  14. Candida Biofilms: Threats, Challenges, and Promising Strategies

    PubMed Central

    Cavalheiro, Mafalda; Teixeira, Miguel Cacho

    2018-01-01

    Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed. PMID:29487851

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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…

  20. 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.

  1. New Promising Strategies in Oncofertility

    PubMed Central

    Hudson, Janella N.; Stanley, Nathanael B.; Nahata, Leena; Bowman-Curci, Meghan; Quinn, Gwendolyn P.

    2017-01-01

    Introduction Approximately 70,000 adolescent and young adults (AYA) are diagnosed with cancer each year. While advancements in treatment have led to improved prognosis and survival for patients, these same treatments can adversely affect AYA reproductive capacity. Localized treatments such as surgery and radiation therapy may affect fertility by removing or damaging reproductive organs, and systemic therapies such as chemotherapy can be toxic to gonads, (ovaries and testicles), thus affecting fertility and/or endocrine function. This can be traumatic for AYA with cancer as survivors often express desire to have genetic children and report feelings of regret or depression as a result of infertility caused by cancer treatments. Areas Covered Emerging technologies in the field of assisted reproductive technology offer new promise for preserving the reproductive capacity of AYA cancer patients prior to treatment as well as providing alternatives for survivors. The following review revisits contemporary approaches to fertility preservation as well newly developing technologies. Expert Commentary There are several advances in ART that hold promise for patients and survivors. However there are challenges that inhibit uptake including poor communication between providers and patients about risks and fertility preservation options; high costs; and lack of insurance coverage for fertility preservation services. PMID:28959743

  2. Do biological-based strategies hold promise to biofouling control in MBRs?

    PubMed

    Malaeb, Lilian; Le-Clech, Pierre; Vrouwenvelder, Johannes S; Ayoub, George M; Saikaly, Pascal E

    2013-10-01

    Biofouling in membrane bioreactors (MBRs) remains a primary challenge for their wider application, despite the growing acceptance of MBRs worldwide. Research studies on membrane fouling are extensive in the literature, with more than 200 publications on MBR fouling in the last 3 years; yet, improvements in practice on biofouling control and management have been remarkably slow. Commonly applied cleaning methods are only partially effective and membrane replacement often becomes frequent. The reason for the slow advancement in successful control of biofouling is largely attributed to the complex interactions of involved biological compounds and the lack of representative-for-practice experimental approaches to evaluate potential effective control strategies. Biofouling is driven by microorganisms and their associated extra-cellular polymeric substances (EPS) and microbial products. Microorganisms and their products convene together to form matrices that are commonly treated as a black box in conventional control approaches. Biological-based antifouling strategies seem to be a promising constituent of an effective integrated control approach since they target the essence of biofouling problems. However, biological-based strategies are in their developmental phase and several questions should be addressed to set a roadmap for translating existing and new information into sustainable and effective control techniques. This paper investigates membrane biofouling in MBRs from the microbiological perspective to evaluate the potential of biological-based strategies in offering viable control alternatives. Limitations of available control methods highlight the importance of an integrated anti-fouling approach including biological strategies. Successful development of these strategies requires detailed characterization of microorganisms and EPS through the proper selection of analytical tools and assembly of results. Existing microbiological/EPS studies reveal a number of

  3. Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer.

    PubMed

    Liu, Qiuping; Luo, Qing; Halim, Alexander; Song, Guanbin

    2017-08-10

    One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Search Strategy to Identify Dental Survival Analysis Articles Indexed in MEDLINE.

    PubMed

    Layton, Danielle M; Clarke, Michael

    2016-01-01

    Articles reporting survival outcomes (time-to-event outcomes) in patients over time are challenging to identify in the literature. Research shows the words authors use to describe their dental survival analyses vary, and that allocation of medical subject headings by MEDLINE indexers is inconsistent. Together, this undermines accurate article identification. The present study aims to develop and validate a search strategy to identify dental survival analyses indexed in MEDLINE (Ovid). A gold standard cohort of articles was identified to derive the search terms, and an independent gold standard cohort of articles was identified to test and validate the proposed search strategies. The first cohort included all 6,955 articles published in the 50 dental journals with the highest impact factors in 2008, of which 95 articles were dental survival articles. The second cohort included all 6,514 articles published in the 50 dental journals with the highest impact factors for 2012, of which 148 were dental survival articles. Each cohort was identified by a systematic hand search. Performance parameters of sensitivity, precision, and number needed to read (NNR) for the search strategies were calculated. Sensitive, precise, and optimized search strategies were developed and validated. The performances of the search strategy maximizing sensitivity were 92% sensitivity, 14% precision, and 7.11 NNR; the performances of the strategy maximizing precision were 93% precision, 10% sensitivity, and 1.07 NNR; and the performances of the strategy optimizing the balance between sensitivity and precision were 83% sensitivity, 24% precision, and 4.13 NNR. The methods used to identify search terms were objective, not subjective. The search strategies were validated in an independent group of articles that included different journals and different publication years. Across the three search strategies, dental survival articles can be identified with sensitivity up to 92%, precision up to 93

  5. 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

  6. Survey of Poetry Reading Strategy as the Modern Tool to Identify Poetry Reading Strategies

    ERIC Educational Resources Information Center

    Ebrahimi, Shirin Shafiei; Zainal, Zaidah

    2016-01-01

    This study examines common strategies that English as a Foreign language (EFL) students employ when reading English poetry. To identify the strategies, a survey was designed for data collection from TESL students. The result shows that students significantly tend to use the strategies that require their creativity to construct new ideas in the…

  7. Strategies Identified as Effective by Mothers During Occupational Performance Coaching.

    PubMed

    Graham, Fiona; Rodger, Sylvia; Ziviani, Jenny; Jones, Virginia

    2016-08-01

    This study examined strategies mothers reported as effective in facilitating children's successful performance in activities they identified as goals during Occupational Performance Coaching (OPC). Twenty-nine mothers of children with occupational performance issues engaged in OPC. A random sample of 44 /157 (28%) coaching sessions were video-recorded from which the audio recording was analyzed using a general inductive approach to explore the nature of strategies reported as effective by mothers. Two major themes emerged: (1) Context-focused; or (2) Child-focused. Context-focused strategies were characterized by mothers' actions that made the performance context more conducive to children's success. The emphasis of mothers' intention in Context-focused strategies was achievement of the task with minimal stress. Context-focused strategies included subthemes of Adjust Manner, Create Distance, Add Structure and Routine, and Teach. Child-focused strategies required higher levels of engagement with children in the application of strategies and were focused on children's skill development. Subthemes included Collaboration and Offer Choice. Mothers engaged in coaching identified strategies which they found supported children's performance, attesting to the existing capacity of mothers in identifying and evaluating effective ways of enhancing children's performance. Findings suggest the potential of coaching as a capacity-building, context-based intervention to improve children's performance.

  8. Strategies to identify natural antisense transcripts.

    PubMed

    Sun, Yulong; Li, Dijie; Zhang, Ru; Peng, Shang; Zhang, Ge; Yang, Tuanmin; Qian, Airong

    2017-01-01

    Natural antisense transcripts, originally considered as transcriptional noises arising from so-called "junk DNA″, are recently recognized as important modulators for gene regulation. They are prevalent in nearly all realms of life and have been found to modulate gene expression positively or negatively. By affecting almost all stages of gene expression range from pre-transcriptional, transcriptional and post-transcriptional to translation, NATs are fundamentally involved in various biological processes. However, compared to increasing huge data from transcriptional analysis especially high-throughput sequencing technologies (such as RNA-seq), limited functional NATs (around 70) are so far reported, which hinder our advanced comprehensive understanding for this field. Hence, efficient strategies for identifying NATs are urgently desired. In this review, we discussed the current strategies for identifying NATs, with a focus on the advantages, disadvantages, and applications of methods isolating functional NATs. Moreover, publicly available databases for NATs were also discussed. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  9. An Automated Summarization Assessment Algorithm for Identifying Summarizing Strategies

    PubMed Central

    Abdi, Asad; Idris, Norisma; Alguliyev, Rasim M.; Aliguliyev, Ramiz M.

    2016-01-01

    Background Summarization is a process to select important information from a source text. Summarizing strategies are the core cognitive processes in summarization activity. Since summarization can be important as a tool to improve comprehension, it has attracted interest of teachers for teaching summary writing through direct instruction. To do this, they need to review and assess the students' summaries and these tasks are very time-consuming. Thus, a computer-assisted assessment can be used to help teachers to conduct this task more effectively. Design/Results This paper aims to propose an algorithm based on the combination of semantic relations between words and their syntactic composition to identify summarizing strategies employed by students in summary writing. An innovative aspect of our algorithm lies in its ability to identify summarizing strategies at the syntactic and semantic levels. The efficiency of the algorithm is measured in terms of Precision, Recall and F-measure. We then implemented the algorithm for the automated summarization assessment system that can be used to identify the summarizing strategies used by students in summary writing. PMID:26735139

  10. 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

  11. Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

    PubMed

    Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

    2017-01-01

    Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries

  12. 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.

  13. 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

  14. 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.

  15. Multipotent mesenchymal stromal cells: A promising strategy to manage alcoholic liver disease

    PubMed Central

    Ezquer, Fernando; Bruna, Flavia; Calligaris, Sebastián; Conget, Paulette; Ezquer, Marcelo

    2016-01-01

    Chronic alcohol consumption is a major cause of liver disease. The term alcoholic liver disease (ALD) refers to a spectrum of mild to severe disorders including steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. With limited therapeutic options, stem cell therapy offers significant potential for these patients. In this article, we review the pathophysiologic features of ALD and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), based on their potential to differentiate into hepatocytes, their immunomodulatory properties, their potential to promote residual hepatocyte regeneration, and their capacity to inhibit hepatic stellate cells. The perfect match between ALD pathogenesis and MSC therapeutic mechanisms, together with encouraging, available preclinical data, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage ALD onset and progression. PMID:26755858

  16. 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…

  17. Tools for Identifying and Prioritizing Evidence-Based Obesity Prevention Strategies, Colorado

    PubMed Central

    Juhl, Ashley L.; Gujral, Indira B.; Hoaglin-Wagner, Andrea L.; Gabella, Barbara A.; McDermott, Kristin M.

    2013-01-01

    Colorado’s adult obesity rate has more than doubled since 1995, prompting its Department of Public Health and Environment to list obesity as its top prevention priority. To initiate comprehensive and effective action, the department used a well-known evidence-based public health framework developed by Brownson and others. This article describes the tools and process developed to conduct 2 of the 7 stages in this framework that challenge public health organizations: reviewing the literature and prioritizing effective strategies from that literature. Forty-five department staff participated in an intensive literature review training to identify physical activity and nutrition strategies that effectively address obesity and worked with external stakeholders to prioritize strategies for the state. Divided into 8 multidisciplinary teams organized by the setting where public health could exert leverage, they scanned the scientific literature to identify potential strategies to implement. These teams were trained to use standardized tools to critique findings, systematically abstract key information, and classify the evidence level for each of 58 identified strategies. Next, departmental subject matter experts and representatives from local public health and nonprofit health agencies selected and applied prioritization criteria to rank the 58 strategies. A team charter, group facilitation tools, and 2 web-based surveys were used in the prioritization stage. This process offered the staff a shared experience to gain hands-on practice completing literature reviews and selecting evidence-based strategies, thereby enhancing Colorado’s obesity prevention efforts and improving public health capacity. Practitioners can use these tools and methodology to replicate this process for other health priorities. PMID:23806801

  18. CRISPR-Cas9 therapeutics in cancer: promising strategies and present challenges.

    PubMed

    Yi, Lang; Li, Jinming

    2016-12-01

    Cancer is characterized by multiple genetic and epigenetic alterations that drive malignant cell proliferation and confer chemoresistance. The ability to correct or ablate such mutations holds immense promise for combating cancer. Recently, because of its high efficiency and accuracy, the CRISPR-Cas9 genome editing technique has been widely used in cancer therapeutic explorations. Several studies used CRISPR-Cas9 to directly target cancer cell genomic DNA in cellular and animal cancer models which have shown therapeutic potential in expanding our anticancer protocols. Moreover, CRISPR-Cas9 can also be employed to fight oncogenic infections, explore anticancer drugs, and engineer immune cells and oncolytic viruses for cancer immunotherapeutic applications. Here, we summarize these preclinical CRISPR-Cas9-based therapeutic strategies against cancer, and discuss the challenges and improvements in translating therapeutic CRISPR-Cas9 into clinical use, which will facilitate better application of this technique in cancer research. Further, we propose potential directions of the CRISPR-Cas9 system in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Climate change and eHealth: a promising strategy for health sector mitigation and adaptation

    PubMed Central

    Holmner, Åsa; Rocklöv, Joacim; Ng, Nawi; Nilsson, Maria

    2012-01-01

    Climate change is one of today's most pressing global issues. Policies to guide mitigation and adaptation are needed to avoid the devastating impacts of climate change. The health sector is a significant contributor to greenhouse gas emissions in developed countries, and its climate impact in low-income countries is growing steadily. This paper reviews and discusses the literature regarding health sector mitigation potential, known and hypothetical co-benefits, and the potential of health information technology, such as eHealth, in climate change mitigation and adaptation. The promising role of eHealth as an adaptation strategy to reduce societal vulnerability to climate change, and the link's between mitigation and adaptation, are also discussed. The topic of environmental eHealth has gained little attention to date, despite its potential to contribute to more sustainable and green health care. A growing number of local and global initiatives on ‘green information and communication technology (ICT)’ are now mentioning eHealth as a promising technology with the potential to reduce emission rates from ICT use. However, the embracing of eHealth is slow because of limitations in technological infrastructure, capacity and political will. Further research on potential emissions reductions and co-benefits with green ICT, in terms of health outcomes and economic effectiveness, would be valuable to guide development and implementation of eHealth in health sector mitigation and adaptation policies. PMID:22679398

  20. Climate change and eHealth: a promising strategy for health sector mitigation and adaptation.

    PubMed

    Holmner, Asa; Rocklöv, Joacim; Ng, Nawi; Nilsson, Maria

    2012-01-01

    Climate change is one of today's most pressing global issues. Policies to guide mitigation and adaptation are needed to avoid the devastating impacts of climate change. The health sector is a significant contributor to greenhouse gas emissions in developed countries, and its climate impact in low-income countries is growing steadily. This paper reviews and discusses the literature regarding health sector mitigation potential, known and hypothetical co-benefits, and the potential of health information technology, such as eHealth, in climate change mitigation and adaptation. The promising role of eHealth as an adaptation strategy to reduce societal vulnerability to climate change, and the link's between mitigation and adaptation, are also discussed. The topic of environmental eHealth has gained little attention to date, despite its potential to contribute to more sustainable and green health care. A growing number of local and global initiatives on 'green information and communication technology (ICT)' are now mentioning eHealth as a promising technology with the potential to reduce emission rates from ICT use. However, the embracing of eHealth is slow because of limitations in technological infrastructure, capacity and political will. Further research on potential emissions reductions and co-benefits with green ICT, in terms of health outcomes and economic effectiveness, would be valuable to guide development and implementation of eHealth in health sector mitigation and adaptation policies.

  1. Traditional Chinese Medicine for Refractory Nephrotic Syndrome: Strategies and Promising Treatments

    PubMed Central

    Tu, Yuan-Chao

    2018-01-01

    Refractory nephrotic syndrome (RNS) is an immune-related kidney disease with poor clinical outcomes. Standard treatments include corticosteroids as the initial therapy and other immunosuppressants as second-line options. A substantial proportion of patients with RNS are resistant to or dependent on immunosuppressive drugs and often experience unremitting edema and proteinuria, cycles of remission and relapse, and/or serious adverse events due to long-term immunosuppression. Traditional Chinese medicine has a long history of treating complicated kidney diseases and holds great potential for providing effective treatments for RNS. This review describes the Chinese medical theories relating to the pathogenesis of RNS and discusses the strategies and treatment options using Chinese herbal medicine. Available preclinical and clinical evidence strongly supports the integration of traditional Chinese medicine and Western medicine for improving the outcome of RNS. Herbal medicine such as Astragalus membranaceus, Stephania tetrandra S. Moore, and Tripterygium wilfordii Hook F can serve as the alternative therapy when patients fail to respond to immunosuppression or as the complementary therapy to improve therapeutic efficacy and reduce side effects of immunosuppressive agents. Wuzhi capsules (Schisandra sphenanthera extract) with tacrolimus and tetrandrine with corticosteroids are two herb-drug combinations that have shown great promise and warrant further studies. PMID:29507594

  2. Distinct Patterns of Cognitive Conflict Dynamics in Promise Keepers and Promise Breakers.

    PubMed

    Calluso, Cinzia; Saulin, Anne; Baumgartner, Thomas; Knoch, Daria

    2018-01-01

    On a daily basis, we see how different people can be in keeping or breaking a given promise. However, we know very little about the cognitive conflict dynamics that underlie the decision to keep or break a promise and whether this is shaped by inter-individual variability. In order to fill this gap, we applied an ecologically valid promise decision task with real monetary consequences for all involved interaction partners and used mouse tracking to identify the dynamic, on-line cognitive processes that underlie the decision to keep or break a promise. Our findings revealed that on average, the process of breaking a promise is associated with largely curved mouse trajectories, while the process of keeping a promise was not, indicating that breaking a promise is associated with a larger conflict. Interestingly, however, this conflict pattern was strongly shaped by individual differences. Individuals who always kept their promises did not show any signs of conflict (i.e., straight mouse trajectories), indicating that they were not tempted by the monetary benefits associated with breaking the promise. In contrast, individuals who did not always keep their promise exhibited a large conflict (i.e., curved mouse trajectories), irrespective of whether they broke or kept their promise. A possible interpretation of these findings is that these individuals were always tempted by the unchosen decision option - the desire to act in a fair manner when breaking the promise and the monetary benefits when keeping the promise. This study provides the first piece of evidence that there are substantial inter-individual differences in cognitive conflict dynamics that underlie the decision to keep or break promises and that mouse tracking is able to illuminate important insights into individual differences in complex human's decision processes.

  3. 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.

  4. Identifying strategies to improve the effectiveness of booster seat laws

    DOT National Transportation Integrated Search

    2008-05-01

    The objective of this project was to identify strategies to improve the effectiveness of booster seat laws. The project explored the possible factors that relate to the use and nonuse of booster seats, and examined the attitudes of law enforcement of...

  5. Identifying Multiple Levels of Discussion-Based Teaching Strategies for Constructing Scientific Models

    ERIC Educational Resources Information Center

    Williams, Grant; Clement, John

    2015-01-01

    This study sought to identify specific types of discussion-based strategies that two successful high school physics teachers using a model-based approach utilized in attempting to foster students' construction of explanatory models for scientific concepts. We found evidence that, in addition to previously documented dialogical strategies that…

  6. Identifying research priorities for effective retention strategies in clinical trials.

    PubMed

    Kearney, Anna; Daykin, Anne; Shaw, Alison R G; Lane, Athene J; Blazeby, Jane M; Clarke, Mike; Williamson, Paula; Gamble, Carrol

    2017-08-31

    The failure to retain patients or collect primary-outcome data is a common challenge for trials and reduces the statistical power and potentially introduces bias into the analysis. Identifying strategies to minimise missing data was the second highest methodological research priority in a Delphi survey of the Directors of UK Clinical Trial Units (CTUs) and is important to minimise waste in research. Our aim was to assess the current retention practices within the UK and priorities for future research to evaluate the effectiveness of strategies to reduce attrition. Seventy-five chief investigators of NIHR Health Technology Assessment (HTA)-funded trials starting between 2009 and 2012 were surveyed to elicit their awareness about causes of missing data within their trial and recommended practices for improving retention. Forty-seven CTUs registered within the UKCRC network were surveyed separately to identify approaches and strategies being used to mitigate missing data across trials. Responses from the current practice surveys were used to inform a subsequent two-round Delphi survey with registered CTUs. A consensus list of retention research strategies was produced and ranked by priority. Fifty out of seventy-five (67%) chief investigators and 33/47 (70%) registered CTUs completed the current practice surveys. Seventy-eight percent of trialists were aware of retention challenges and implemented strategies at trial design. Patient-initiated withdrawal was the most common cause of missing data. Registered CTUs routinely used newsletters, timeline of participant visits, and telephone reminders to mitigate missing data. Whilst 36 out of 59 strategies presented had been formally or informally evaluated, some frequently used strategies, such as site initiation training, have had no research to inform practice. Thirty-five registered CTUs (74%) participated in the Delphi survey. Research into the effectiveness of site initiation training, frequency of patient contact

  7. Identifying species conservation strategies to reduce disease-associated declines

    USGS Publications Warehouse

    Gerber, Brian D.; Converse, Sarah J.; Muths, Erin L.; Crockett, Harry J.; Mosher, Brittany A.; Bailey, Larissa L.

    2018-01-01

    Emerging infectious diseases (EIDs) are a salient threat to many animal taxa, causing local and global extinctions, altering communities and ecosystem function. The EID chytridiomycosis is a prominent driver of amphibian declines, which is caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). To guide conservation policy, we developed a predictive decision-analytic model that combines empirical knowledge of host-pathogen metapopulation dynamics with expert judgment regarding effects of management actions, to select from potential conservation strategies. We apply our approach to a boreal toad (Anaxyrus boreas boreas) and Bd system, identifying optimal strategies that balance tradeoffs in maximizing toad population persistence and landscape-level distribution, while considering costs. The most robust strategy is expected to reduce the decline of toad breeding sites from 53% to 21% over 50 years. Our findings are incorporated into management policy to guide conservation planning. Our online modeling application provides a template for managers of other systems challenged by EIDs.

  8. 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…

  9. Childhood executive function inventory (CHEXI): a promising measure for identifying young children with ADHD?

    PubMed

    Thorell, Lisa B; Eninger, Lilianne; Brocki, Karin C; Bohlin, Gunilla

    2010-01-01

    The present study investigated whether the Childhood Executive Function Inventory (CHEXI) can discriminate between young children fulfilling the diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD) and normally developing children. Unlike other executive function rating instruments, the CHEXI focuses specifically on inhibitory control and working memory, without including items that overlap with the diagnostic criteria of ADHD. The CHEXI was found to discriminate very well between children fulfilling the criteria for ADHD and normally developing children, also when controlling for the effect of IQ and socioeconomic status (SES). Both sensitivity and specificity of the two CHEXI subscales were shown to be high using either parent or teacher ratings. The highest overall classification rate was found for parent ratings on the inhibition subscale, with sensitivity and specificity reaching 93.3. To summarize, the CHEXI should be considered a promising measure for identifying young children with ADHD, although it is for future research to determine whether the CHEXI can be successfully used to also discriminate between different psychopathological groups.

  10. Validation of a search strategy to identify nutrition trials in PubMed using the relative recall method.

    PubMed

    Durão, Solange; Kredo, Tamara; Volmink, Jimmy

    2015-06-01

    To develop, assess, and maximize the sensitivity of a search strategy to identify diet and nutrition trials in PubMed using relative recall. We developed a search strategy to identify diet and nutrition trials in PubMed. We then constructed a gold standard reference set to validate the identified trials using the relative recall method. Relative recall was calculated by dividing the number of references from the gold standard our search strategy identified by the total number of references in the gold standard. Our gold standard comprised 298 trials, derived from 16 included systematic reviews. The initial search strategy identified 242 of 298 references, with a relative recall of 81.2% [95% confidence interval (CI): 76.3%, 85.5%]. We analyzed titles and abstracts of the 56 missed references for possible additional terms. We then modified the search strategy accordingly. The relative recall of the final search strategy was 88.6% (95% CI: 84.4%, 91.9%). We developed a search strategy to identify diet and nutrition trials in PubMed with a high relative recall (sensitivity). This could be useful for establishing a nutrition trials register to support the conduct of future research, including systematic reviews. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. 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…

  12. Identifying Strategies Programs Adopt to Meet Healthy Eating and Physical Activity Standards in Afterschool Programs.

    PubMed

    Weaver, Robert G; Moore, Justin B; Turner-McGrievy, Brie; Saunders, Ruth; Beighle, Aaron; Khan, M Mahmud; Chandler, Jessica; Brazendale, Keith; Randell, Allison; Webster, Collin; Beets, Michael W

    2017-08-01

    The YMCA of USA has adopted Healthy Eating and Physical Activity (HEPA) Standards for its afterschool programs (ASPs). Little is known about strategies YMCA ASPs are implementing to achieve Standards and these strategies' effectiveness. (1) Identify strategies implemented in YMCA ASPs and (2) evaluate the relationship between strategy implementation and meeting Standards. HEPA was measured via accelerometer (moderate-to-vigorous-physical-activity [MVPA]) and direct observation (snacks served) in 20 ASPs. Strategies were identified and mapped onto a capacity building framework ( Strategies To Enhance Practice [STEPs]). Mixed-effects regression estimated increases in HEPA outcomes as implementation increased. Model-implied estimates were calculated for high (i.e., highest implementation score achieved), moderate (median implementation score across programs), and low (lowest implementation score achieved) implementation for both HEPA separately. Programs implemented a variety of strategies identified in STEPs. For every 1-point increase in implementation score 1.45% (95% confidence interval = 0.33% to 2.55%, p ≤ .001) more girls accumulated 30 min/day of MVPA and fruits and/or vegetables were served on 0.11 more days (95% confidence interval = 0.11-0.45, p ≤ .01). Relationships between implementation and other HEPA outcomes did not reach statistical significance. Still regression estimates indicated that desserts are served on 1.94 fewer days (i.e., 0.40 vs. 2.34) in the highest implementing program than the lowest implementing program and water is served 0.73 more days (i.e., 2.37 vs. 1.64). Adopting HEPA Standards at the national level does not lead to changes in routine practice in all programs. Practical strategies that programs could adopt to more fully comply with the HEPA Standards are identified.

  13. Making processes reliable: a validated pubmed search strategy for identifying new or emerging technologies.

    PubMed

    Varela-Lema, Leonora; Punal-Riobóo, Jeanette; Acción, Beatriz Casal; Ruano-Ravina, Alberto; García, Marisa López

    2012-10-01

    Horizon scanning systems need to handle a wide range of sources to identify new or emerging health technologies. The objective of this study is to develop a validated Medline bibliographic search strategy (PubMed search engine) to systematically identify new or emerging health technologies. The proposed Medline search strategy combines free text terms commonly used in article titles to denote innovation within index terms that make reference to the specific fields of interest. Efficacy was assessed by running the search over a period of 1 year (2009) and analyzing its retrieval performance (number and characteristics). For comparison purposes, all article abstracts published during 2009 in six preselected key research journals and eight high impact surgery journals were scanned. Sensitivity was defined as the proportion of relevant new or emerging technologies published in key journals that would be identified in the search strategy within the first 2 years of publication. The search yielded 6,228 abstracts of potentially new or emerging technologies. Of these, 459 were classified as new or emerging (383 truly new or emerging and 76 new indications). The scanning of 12,061 journal abstracts identified 35 relevant new or emerging technologies. Of these, twenty-nine were located within the Medline search strategy during the first 2 years of publication (sensitivity = 83 percent). The current search strategy, validated against key journals, has demonstrated to be effective for horizon scanning. Even though it can require adaptations depending on the scope of the horizon scanning system, it could serve to simplify and standardize scanning processes.

  14. Special Strategies for Educating Disadvantaged Children. Urban and Suburban/Rural. First Year Report.

    ERIC Educational Resources Information Center

    Stringfield, Sam; And Others

    This volume presents methods and first-year findings from the urban and suburban/rural studies of Special Strategies for Educating Disadvantaged Children, a 3-year project that is collecting case study data on 10 different strategies identified as holding promise for educating this group of children. Data collected by Special Strategies involve…

  15. Identifying Strategies Programs Adopt to Meet Healthy Eating and Physical Activity Standards in Afterschool Programs

    ERIC Educational Resources Information Center

    Weaver, Robert G.; Moore, Justin B.; Turner-McGrievy, Brie; Saunders, Ruth; Beighle, Aaron; Khan, M. Mahmud; Chandler, Jessica; Brazendale, Keith; Randell, Allison; Webster, Collin; Beets, Michael W.

    2017-01-01

    Background: The YMCA of USA has adopted Healthy Eating and Physical Activity (HEPA) Standards for its afterschool programs (ASPs). Little is known about strategies YMCA ASPs are implementing to achieve Standards and these strategies' effectiveness. Aims: (1) Identify strategies implemented in YMCA ASPs and (2) evaluate the relationship between…

  16. America Promises to Come Back: A New National Strategy

    DTIC Science & Technology

    1990-12-26

    plants, and other government capa- bilities, should be studied by a Blue-Ribbon Panel assisted by 61 industria .. and proressional associations. This ertort...Conference of the International Institute for Strate- gic Studies (IISS) on September 6th, explained that the new strategic concepts would form the basis of...Reserve forces which could be returned within a reasonable period. This may not be the case , and America’s promise to return may indeed be within the

  17. 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

  18. Combined Gemcitabine and Metronidazole Is a Promising Therapeutic Strategy for Cancer Stem-like Cholangiocarcinoma.

    PubMed

    Kawamoto, Makoto; Umebayashi, Masayo; Tanaka, Hiroto; Koya, Norihiro; Nakagawa, Sinichiro; Kawabe, Ken; Onishi, Hideya; Nakamura, Masafumi; Morisaki, Takashi

    2018-05-01

    Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA. Using these cell lines, we analyzed the impacts of MNZ for cancer stem cell markers, invasiveness, and chemosensitivity. MNZ reduced ALDH activity in GEM-resistant CCA cells, leading to decreased invasiveness and enhanced chemosensitivity. MNZ diminished the invasiveness by inducing mesenchymal-epithelial transition and enhancing chemosensitivity by increasing ENT1 (equilibrative nucleoside transporter 1) and reducing RRM1 (ribonucleotide reductase M1). MNZ reduced cancer stemness in GEM-resistant CCA cells. Combined GEM and MNZ would be a promising therapeutic strategy for cancer stem-like CAA. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables.

    PubMed

    Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C; Downing, James R; Lamba, Jatinder

    2009-08-15

    In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org.

  20. Nonpharmacological, Blood Conservation Techniques for Preventing Neonatal Anemia—Effective and Promising Strategies for Reducing Transfusion

    PubMed Central

    Carroll, Patrick D.; Widness, John A.

    2012-01-01

    The development of anemia after birth in very premature, critically ill newborn infants is a universal well-described phenomenon. Although preventing anemia in this population, along with efforts to establish optimal red blood cell (RBC) transfusion and pharmacologic therapy continue to be actively investigated, the present review focuses exclusively on nonpharmacological approaches to the prevention and treatment of neonatal anemia. We begin with an overview of topics relevant to nonpharmacological techniques. These topics include neonatal and fetoplacental hemoglobin levels and blood volumes, clinical and laboratory practices applied in critically ill neonates, and current RBC transfusion practice guidelines. This is followed by a discussion of the most effective and promising nonpharmacological blood conservation strategies and techniques. Fortunately, many of these techniques are feasible in most neonatal intensive care units. When applied together, these techniques are more effective than existing pharmacotherapies in significantly decreasing neonatal RBC transfusions. They include increasing hemoglobin endowment and circulating blood volume at birth; removing less blood for laboratory testing; and optimizing nutrition. PMID:22818543

  1. Inclusive Branding Strategies for Domestic Violence Agencies: Embracing Opportunities to Reach and Better Serve Male-Identified Survivors.

    PubMed

    Dewey, Morgan; Heiss, Sarah N

    2018-05-01

    Successful strategies for branding that are inclusive of male-identified survivors were identified in this qualitative study through semi-structured interviews with leaders from six domestic violence agencies across the United States: four represented traditional domestic violence agencies and two represented specialized agencies with expertise in providing services to nontraditional survivors. The strategic implementation of (a) inclusive language, (b) visual diversity, (c) community outreach, and (d) communication channels emerged as successful strategies in branding in an inclusive way for male-identified survivors. The implementation of these successful strategies provides the opportunity for domestic violence agencies to create an inclusive environment for male-identified survivors and would contribute to a paradigm shift in how domestic violence is viewed.

  2. 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.

  3. Strategies to Identify the Lynch Syndrome Among Patients With Colorectal Cancer

    PubMed Central

    Ladabaum, Uri; Wang, Grace; Terdiman, Jonathan; Blanco, Amie; Kuppermann, Miriam; Boland, C. Richard; Ford, James; Elkin, Elena; Phillips, Kathryn A.

    2013-01-01

    Background Testing has been advocated for all persons with newly diagnosed colorectal cancer to identify families with the Lynch syndrome, an autosomal dominant cancer-predisposition syndrome that is a paradigm for personalized medicine. Objective To estimate the effectiveness and cost-effectiveness of strategies to identify the Lynch syndrome, with attention to sex, age at screening, and differential effects for probands and relatives. Design Markov model that incorporated risk for colorectal, endometrial, and ovarian cancers. Data Sources Published literature. Target Population All persons with newly diagnosed colorectal cancer and their relatives. Time Horizon Lifetime. Perspective Third-party payer. Intervention Strategies based on clinical criteria, prediction algorithms, tumor testing, or up-front germline mutation testing, followed by tailored screening and risk-reducing surgery. Outcome Measures Life-years, cancer cases and deaths, costs, and incremental cost-effectiveness ratios. Results of Base-Case Analysis The benefit of all strategies accrued primarily to relatives with a mutation associated with the Lynch syndrome, particularly women, whose life expectancy could increase by approximately 4 years with hysterectomy and salpingo-oophorectomy and adherence to colorectal cancer screening recommendations. At current rates of germline testing, screening, and prophylactic surgery, the strategies reduced deaths from colorectal cancer by 7% to 42% and deaths from endometrial and ovarian cancer by 1% to 6%. Among tumor-testing strategies, immunohistochemistry followed by BRAF mutation testing was preferred, with an incremental cost-effectiveness ratio of $36 200 per life-year gained. Results of Sensitivity Analysis The number of relatives tested per proband was a critical determinant of both effectiveness and cost-effectiveness, with testing of 3 to 4 relatives required for most strategies to meet a threshold of $50 000 per life-year gained. Immunohistochemistry

  4. Biased and unbiased strategies to identify biologically active small molecules.

    PubMed

    Abet, Valentina; Mariani, Angelica; Truscott, Fiona R; Britton, Sébastien; Rodriguez, Raphaël

    2014-08-15

    Small molecules are central players in chemical biology studies. They promote the perturbation of cellular processes underlying diseases and enable the identification of biological targets that can be validated for therapeutic intervention. Small molecules have been shown to accurately tune a single function of pluripotent proteins in a reversible manner with exceptional temporal resolution. The identification of molecular probes and drugs remains a worthy challenge that can be addressed by the use of biased and unbiased strategies. Hypothesis-driven methodologies employs a known biological target to synthesize complementary hits while discovery-driven strategies offer the additional means of identifying previously unanticipated biological targets. This review article provides a general overview of recent synthetic frameworks that gave rise to an impressive arsenal of biologically active small molecules with unprecedented cellular mechanisms. Copyright © 2014. Published by Elsevier Ltd.

  5. 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.

  6. 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

  7. 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.

  8. Identifying Strategy Use in Category Learning Tasks: A Case for More Diagnostic Data and Models

    ERIC Educational Resources Information Center

    Donkin, Chris; Newell, Ben R.; Kalish, Mike; Dunn, John C.; Nosofsky, Robert M.

    2015-01-01

    The strength of conclusions about the adoption of different categorization strategies--and their implications for theories about the cognitive and neural bases of category learning--depend heavily on the techniques for identifying strategy use. We examine performance in an often-used "information-integration" category structure and…

  9. Nonpharmacological, blood conservation techniques for preventing neonatal anemia--effective and promising strategies for reducing transfusion.

    PubMed

    Carroll, Patrick D; Widness, John A

    2012-08-01

    The development of anemia after birth in very premature, critically ill newborn infants is a universal well-described phenomenon. Although preventing anemia in this population, along with efforts to establish optimal red blood cell (RBC) transfusion and pharmacologic therapy continue to be actively investigated, the present review focuses exclusively on nonpharmacological approaches to the prevention and treatment of neonatal anemia. We begin with an overview of topics relevant to nonpharmacological techniques. These topics include neonatal and fetoplacental hemoglobin levels and blood volumes, clinical and laboratory practices applied in critically ill neonates, and current RBC transfusion practice guidelines. This is followed by a discussion of the most effective and promising nonpharmacological blood conservation strategies and techniques. Fortunately, many of these techniques are feasible in most neonatal intensive care units. When applied together, these techniques are more effective than existing pharmacotherapies in significantly decreasing neonatal RBC transfusions. They include increasing hemoglobin endowment and circulating blood volume at birth; removing less blood for laboratory testing; and optimizing nutrition. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Seeking informed consent to Phase I cancer clinical trials: identifying oncologists' communication strategies.

    PubMed

    Brown, Richard; Bylund, Carma L; Siminoff, Laura A; Slovin, Susan F

    2011-04-01

    Phase I clinical trials are the gateway to effective new cancer treatments. Many physicians have difficulty when discussing Phase I clinical trials. Research demonstrates evidence of suboptimal communication. Little is known about communication strategies used by oncologists when recruiting patients for Phase I trials. We analyzed audio recorded Phase I consultations to identify oncologists' communication strategies. Subjects were consecutive cancer patients from six medical oncologists attending one of three outpatient clinics at a major Cancer Center in the United States. Sixteen patients signed informed consent for audio recording of their consultations in which a Phase I study was discussed. These were transcribed in full and analyzed to identify communication strategies. Six communication themes emerged from the analysis: (1) orienting, (2) educating patients, (3) describing uncertainty and prognosis, (4) persuading, (5) decision making, and (6) making a treatment recommendation. As expected, although there was some common ground between communication in Phase I and the Phase II and III settings, there were distinct differences. Oncologists used persuasive communication, made explicit recommendations, or implicitly expressed a treatment preference and were choice limiting. This highlights the complexity of discussing Phase I trials and the need to develop strategies to aid oncologists and patients in these difficult conversations. Patient centered communication that values patient preferences while preserving the oncologist's agenda can be a helpful approach to these discussions. Copyright © 2010 John Wiley & Sons, Ltd.

  11. 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

  12. PROMISE: a tool to identify genomic features with a specific biologically interesting pattern of associations with multiple endpoint variables

    PubMed Central

    Pounds, Stan; Cheng, Cheng; Cao, Xueyuan; Crews, Kristine R.; Plunkett, William; Gandhi, Varsha; Rubnitz, Jeffrey; Ribeiro, Raul C.; Downing, James R.; Lamba, Jatinder

    2009-01-01

    Motivation: In some applications, prior biological knowledge can be used to define a specific pattern of association of multiple endpoint variables with a genomic variable that is biologically most interesting. However, to our knowledge, there is no statistical procedure designed to detect specific patterns of association with multiple endpoint variables. Results: Projection onto the most interesting statistical evidence (PROMISE) is proposed as a general procedure to identify genomic variables that exhibit a specific biologically interesting pattern of association with multiple endpoint variables. Biological knowledge of the endpoint variables is used to define a vector that represents the biologically most interesting values for statistics that characterize the associations of the endpoint variables with a genomic variable. A test statistic is defined as the dot-product of the vector of the observed association statistics and the vector of the most interesting values of the association statistics. By definition, this test statistic is proportional to the length of the projection of the observed vector of correlations onto the vector of most interesting associations. Statistical significance is determined via permutation. In simulation studies and an example application, PROMISE shows greater statistical power to identify genes with the interesting pattern of associations than classical multivariate procedures, individual endpoint analyses or listing genes that have the pattern of interest and are significant in more than one individual endpoint analysis. Availability: Documented R routines are freely available from www.stjuderesearch.org/depts/biostats and will soon be available as a Bioconductor package from www.bioconductor.org. Contact: stanley.pounds@stjude.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19528086

  13. 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

  14. Promising Electric Aircraft Drive Systems

    NASA Technical Reports Server (NTRS)

    Dudley, Michael R.

    2010-01-01

    An overview of electric aircraft propulsion technology performance thresholds for key power system components is presented. A weight comparison of electric drive systems with equivalent total delivered energy is made to help identify component performance requirements, and promising research and development opportunities.

  15. Validity and Reliability of a Systematic Database Search Strategy to Identify Publications Resulting From Pharmacy Residency Research Projects.

    PubMed

    Kwak, Namhee; Swan, Joshua T; Thompson-Moore, Nathaniel; Liebl, Michael G

    2016-08-01

    This study aims to develop a systematic search strategy and test its validity and reliability in terms of identifying projects published in peer-reviewed journals as reported by residency graduates through an online survey. This study was a prospective blind comparison to a reference standard. Pharmacy residency projects conducted at the study institution between 2001 and 2012 were included. A step-wise, systematic procedure containing up to 8 search strategies in PubMed and EMBASE for each project was created using the names of authors and abstract keywords. In order to further maximize sensitivity, complex phrases with multiple variations were truncated to the root word. Validity was assessed by obtaining information on publications from an online survey deployed to residency graduates. The search strategy identified 13 publications (93% sensitivity, 100% specificity, and 99% accuracy). Both methods identified a similar proportion achieving publication (19.7% search strategy vs 21.2% survey, P = 1.00). Reliability of the search strategy was affirmed by the perfect agreement between 2 investigators (k = 1.00). This systematic search strategy demonstrated a high sensitivity, specificity, and accuracy for identifying publications resulting from pharmacy residency projects using information available in residency conference abstracts. © The Author(s) 2015.

  16. Identifying tacit strategies in aircraft maneuvers

    NASA Technical Reports Server (NTRS)

    Lewis, Charles M.; Heidorn, P. B.

    1991-01-01

    Two machine-learning methods are presently used to characterize the avoidance strategies used by skilled pilots in simulated aircraft encounters, and a general framework for the characterization of the strategic components of skilled behavior via qualitative representation of situations and responses is presented. Descriptions of pilot maneuvers that were 'conceptually equivalent' were ascertained by a concept-learning algorithm in conjunction with a classifier system that employed a generic algorithm; satisficing and 'buggy' strategies were thereby revealed.

  17. 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…

  18. 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

  19. Strategies for increasing fruit and vegetable intake in grocery stores and communities: policy, pricing, and environmental change.

    PubMed

    Glanz, Karen; Yaroch, Amy L

    2004-09-01

    Grocery stores and community settings are important and promising venues for environmental, policy, and pricing initiatives to increase fruit and vegetable intake. This article examines supermarket-based and community environmental, policy, and pricing strategies for increasing intake of fruits and vegetables and identifies promising strategies, research needs, and innovative opportunities for the future. The strategies, examples, and research reported here were identified through an extensive search of published journal articles, reports, and inquiries to leaders in the field. Recommendations were expanded with input from participants in the CDC/ACS-sponsored Fruit and Vegetable, Environment Policy and Pricing Workshop held in September of 2002. Four key types of grocery-store-based interventions include point-of-purchase (POP) information; reduced prices and coupons; increased availability, variety, and convenience; and promotion and advertising. There is strong support for the feasibility of these approaches and modest evidence of their efficacy in influencing eating behavior. Church-based programs, child care center policies, and multisectoral community approaches show promise. Both descriptive and intervention research are needed to develop and evaluate more effective environmental strategies to increase F&V intake in grocery stores and communities. Innovative strategies, partnerships, grass roots action involving economic development for low-income communities, and sustainability are important considerations.

  20. Looking Ahead Toward Community-Level Strategies to Prevent Sexual Violence

    PubMed Central

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

    2018-01-01

    The Division of Violence Prevention within CDC’s National Center for Injury Prevention and Control recently undertook a systematic review of primary prevention strategies for sexual violence (SV) perpetration. This review identified the lack of community-level strategies to prevent SV as a critical gap in the literature. Community-level strategies function by modifying the characteristics of settings (e.g., schools, workplaces, neighborhoods) that increase the risk for violence victimization and perpetration. Identification of evidence-based strategies at the community level would allow implementation of ecologic approaches to SV prevention with a greater potential for reducing the prevalence of SV perpetration. The field will face several challenges in identifying and evaluating the effectiveness of promising community-level strategies to prevent SV. These challenges include limited knowledge of community-level and societal-level risk factors for SV, a lack of theoretical or empirical guidance in the SV literature for identification of promising community-level approaches, and challenges in evaluating SV outcomes at the community level. Recognition of these challenges should guide future research and foster dialogue within the SV prevention field. The development and evaluation of community-level approaches to SV prevention represent a vital and logical next step toward the implementation of effective, multilevel prevention efforts and a population-level reduction in the prevalence of SV. PMID:22185587

  1. 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.

  2. Exploring critical pathways for urban water management to identify robust strategies under deep uncertainties.

    PubMed

    Urich, Christian; Rauch, Wolfgang

    2014-12-01

    Long-term projections for key drivers needed in urban water infrastructure planning such as climate change, population growth, and socio-economic changes are deeply uncertain. Traditional planning approaches heavily rely on these projections, which, if a projection stays unfulfilled, can lead to problematic infrastructure decisions causing high operational costs and/or lock-in effects. New approaches based on exploratory modelling take a fundamentally different view. Aim of these is, to identify an adaptation strategy that performs well under many future scenarios, instead of optimising a strategy for a handful. However, a modelling tool to support strategic planning to test the implication of adaptation strategies under deeply uncertain conditions for urban water management does not exist yet. This paper presents a first step towards a new generation of such strategic planning tools, by combing innovative modelling tools, which coevolve the urban environment and urban water infrastructure under many different future scenarios, with robust decision making. The developed approach is applied to the city of Innsbruck, Austria, which is spatially explicitly evolved 20 years into the future under 1000 scenarios to test the robustness of different adaptation strategies. Key findings of this paper show that: (1) Such an approach can be used to successfully identify parameter ranges of key drivers in which a desired performance criterion is not fulfilled, which is an important indicator for the robustness of an adaptation strategy; and (2) Analysis of the rich dataset gives new insights into the adaptive responses of agents to key drivers in the urban system by modifying a strategy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. A Quantitative Study Identifying Political Strategies Used by Principals of Dual Language Programs

    ERIC Educational Resources Information Center

    Girard, Guadalupe

    2017-01-01

    Purpose. The purpose of this quantitative study was to identify the external and internal political strategies used by principals that allow them to successfully navigate the political environment surrounding dual language programs. Methodology. This quantitative study used descriptive research to collect, analyze, and report data that identified…

  4. Identifying protein complexes based on brainstorming strategy.

    PubMed

    Shen, Xianjun; Zhou, Jin; Yi, Li; Hu, Xiaohua; He, Tingting; Yang, Jincai

    2016-11-01

    Protein complexes comprising of interacting proteins in protein-protein interaction network (PPI network) play a central role in driving biological processes within cells. Recently, more and more swarm intelligence based algorithms to detect protein complexes have been emerging, which have become the research hotspot in proteomics field. In this paper, we propose a novel algorithm for identifying protein complexes based on brainstorming strategy (IPC-BSS), which is integrated into the main idea of swarm intelligence optimization and the improved K-means algorithm. Distance between the nodes in PPI network is defined by combining the network topology and gene ontology (GO) information. Inspired by human brainstorming process, IPC-BSS algorithm firstly selects the clustering center nodes, and then they are separately consolidated with the other nodes with short distance to form initial clusters. Finally, we put forward two ways of updating the initial clusters to search optimal results. Experimental results show that our IPC-BSS algorithm outperforms the other classic algorithms on yeast and human PPI networks, and it obtains many predicted protein complexes with biological significance. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. [Strategies to identify supernumerary chromosomal markers in constitutional cytogenetics].

    PubMed

    Douet-Guilbert, N; Basinko, A; Le Bris, M-J; Herry, A; Morel, F; De Braekeleer, M

    2008-09-01

    Supernumerary marker chromosomes (SMCs) are defined as extrastructurally abnormal chromosomes which origin and composition cannot be determined by conventional cytogenetics. SMCs are an heterogeneous group of abnormalities concerning all chromosomes with variable structure and size and are associated with phenotypic heterogeneity. The characterisation of SMCs is of utmost importance for genetic counselling. Different molecular techniques are used to identify chromosomal material present in markers such as 24-colour FISH (MFISH, SKY), centromere specific multicolour FISH (cenMFISH) and derivatives (acroMFISH, subcenMFISH), comparative genomic hybridisation (CGH), arrayCGH, and targeted FISH techniques (banding techniques, whole chromosome painting...). Based on the morphology of SMC with conventional cytogenetic and clinical data, we tried to set up different molecular strategies with all available techniques.

  6. Identifying Stride-To-Stride Control Strategies in Human Treadmill Walking

    PubMed Central

    Dingwell, Jonathan B.; Cusumano, Joseph P.

    2015-01-01

    Variability is ubiquitous in human movement, arising from internal and external noise, inherent biological redundancy, and from the neurophysiological control actions that help regulate movement fluctuations. Increased walking variability can lead to increased energetic cost and/or increased fall risk. Conversely, biological noise may be beneficial, even necessary, to enhance motor performance. Indeed, encouraging more variability actually facilitates greater improvements in some forms of locomotor rehabilitation. Thus, it is critical to identify the fundamental principles humans use to regulate stride-to-stride fluctuations in walking. This study sought to determine how humans regulate stride-to-stride fluctuations in stepping movements during treadmill walking. We developed computational models based on pre-defined goal functions to compare if subjects, from each stride to the next, tried to maintain the same speed as the treadmill, or instead stay in the same position on the treadmill. Both strategies predicted average behaviors empirically indistinguishable from each other and from that of humans. These strategies, however, predicted very different stride-to-stride fluctuation dynamics. Comparisons to experimental data showed that human stepping movements were generally well-predicted by the speed-control model, but not by the position-control model. Human subjects also exhibited no indications they corrected deviations in absolute position only intermittently: i.e., closer to the boundaries of the treadmill. Thus, humans clearly do not adopt a control strategy whose primary goal is to maintain some constant absolute position on the treadmill. Instead, humans appear to regulate their stepping movements in a way most consistent with a strategy whose primary goal is to try to maintain the same speed as the treadmill at each consecutive stride. These findings have important implications both for understanding how biological systems regulate walking in general and

  7. Consumer-identified barriers and strategies for optimizing technology use in the workplace.

    PubMed

    De Jonge, Desleigh M; Rodger, Sylvia A

    2006-01-01

    This article explores the experiences of 26 assistive technology (AT) users having a range of physical impairments as they optimized their use of technology in the workplace. A qualitative research design was employed using in-depth, open-ended interviews and observations of AT users in the workplace. Participants identified many factors that limited their use of technology such as discomfort and pain, limited knowledge of the technology's features, and the complexity of the technology. The amount of time required for training, limited work time available for mastery, cost of training and limitations of the training provided, resulted in an over-reliance on trial and error and informal support networks and a sense of isolation. AT users enhanced their use of technology by addressing the ergonomics of the workstation and customizing the technology to address individual needs and strategies. Other key strategies included tailored training and learning support as well as opportunities to practice using the technology and explore its features away from work demands. This research identified structures important for effective AT use in the workplace which need to be put in place to ensure that AT users are able to master and optimize their use of technology.

  8. Diarrhoea prevention in Bolivia through point-of-use water treatment and safe storage: a promising new strategy.

    PubMed Central

    Quick, R. E.; Venczel, L. V.; Mintz, E. D.; Soleto, L.; Aparicio, J.; Gironaz, M.; Hutwagner, L.; Greene, K.; Bopp, C.; Maloney, K.; Chavez, D.; Sobsey, M.; Tauxe, R. V.

    1999-01-01

    A novel water quality intervention that consists of point-of-use water disinfection, safe storage and community education was field tested in Bolivia. A total of 127 households in two periurban communities were randomized into intervention and control groups, surveyed and the intervention was distributed. Monthly water quality testing and weekly diarrhoea surveillance were conducted. Over a 5-month period, intervention households had 44% fewer diarrhoea episodes than control households (P = 0.002). Infants < 1 year old (P = 0.05) and children 5-14 years old (P = 0.01) in intervention households had significantly less diarrhoea than control children. Campylobacter was less commonly isolated from intervention than control patients (P = 0.02). Stored water in intervention households was less contaminated with Escherichia coli than stored water in control households (P < 0.0001). Intervention households exhibited less E. coli contamination of stored water and less diarrhoea than control households. This promising new strategy may have broad applicability for waterborne disease prevention. PMID:10098789

  9. 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…

  10. 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.

  11. 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

  12. A new computational strategy for identifying essential proteins based on network topological properties and biological information.

    PubMed

    Qin, Chao; Sun, Yongqi; Dong, Yadong

    2017-01-01

    Essential proteins are the proteins that are indispensable to the survival and development of an organism. Deleting a single essential protein will cause lethality or infertility. Identifying and analysing essential proteins are key to understanding the molecular mechanisms of living cells. There are two types of methods for predicting essential proteins: experimental methods, which require considerable time and resources, and computational methods, which overcome the shortcomings of experimental methods. However, the prediction accuracy of computational methods for essential proteins requires further improvement. In this paper, we propose a new computational strategy named CoTB for identifying essential proteins based on a combination of topological properties, subcellular localization information and orthologous protein information. First, we introduce several topological properties of the protein-protein interaction (PPI) network. Second, we propose new methods for measuring orthologous information and subcellular localization and a new computational strategy that uses a random forest prediction model to obtain a probability score for the proteins being essential. Finally, we conduct experiments on four different Saccharomyces cerevisiae datasets. The experimental results demonstrate that our strategy for identifying essential proteins outperforms traditional computational methods and the most recently developed method, SON. In particular, our strategy improves the prediction accuracy to 89, 78, 79, and 85 percent on the YDIP, YMIPS, YMBD and YHQ datasets at the top 100 level, respectively.

  13. 4-H Alumni: Techniques and Strategies of Identifying and Involving 4-H Alumni.

    ERIC Educational Resources Information Center

    Reese, Cheryl C.

    Techniques and strategies of identifying and involving 4-H alumni are discussed and described via a model of the Tennessee 4-H Alumni, Inc., which began in 1975. Following an introduction, the guide begins with a section on finding and organizing alumni which encompasses alumni organizers (organizational decisions, model alumni association);…

  14. Identifying conservation priorities and management strategies based on ecosystem services to improve urban sustainability in Harbin, China.

    PubMed

    Qu, Yi; Lu, Ming

    2018-01-01

    Rapid urbanization and agricultural development has resulted in the degradation of ecosystems, while also negatively impacting ecosystem services (ES) and urban sustainability. Identifying conservation priorities for ES and applying reasonable management strategies have been found to be effective methods for mitigating this phenomenon. The purpose of this study is to propose a comprehensive framework for identifying ES conservation priorities and associated management strategies for these planning areas. First, we incorporated 10 ES indicators within a systematic conservation planning (SCP) methodology in order to identify ES conservation priorities with high irreplaceability values based on conservation target goals associated with the potential distribution of ES indicators. Next, we assessed the efficiency of the ES conservation priorities for meeting the designated conservation target goals. Finally, ES conservation priorities were clustered into groups using a K-means clustering analysis in an effort to identify the dominant ES per location before formulating management strategies. We effectively identified 12 ES priorities to best represent conservation target goals for the ES indicators. These 12 priorities had a total areal coverage of 13,364 km 2 representing 25.16% of the study area. The 12 priorities were further clustered into five significantly different groups ( p -values between groups < 0.05), which helped to refine management strategies formulated to best enhance ES across the study area. The proposed method allows conservation and management plans to easily adapt to a wide variety of quantitative ES target goals within urban and agricultural areas, thereby preventing urban and agriculture sprawl and guiding sustainable urban development.

  15. Identifying conservation priorities and management strategies based on ecosystem services to improve urban sustainability in Harbin, China

    PubMed Central

    2018-01-01

    Rapid urbanization and agricultural development has resulted in the degradation of ecosystems, while also negatively impacting ecosystem services (ES) and urban sustainability. Identifying conservation priorities for ES and applying reasonable management strategies have been found to be effective methods for mitigating this phenomenon. The purpose of this study is to propose a comprehensive framework for identifying ES conservation priorities and associated management strategies for these planning areas. First, we incorporated 10 ES indicators within a systematic conservation planning (SCP) methodology in order to identify ES conservation priorities with high irreplaceability values based on conservation target goals associated with the potential distribution of ES indicators. Next, we assessed the efficiency of the ES conservation priorities for meeting the designated conservation target goals. Finally, ES conservation priorities were clustered into groups using a K-means clustering analysis in an effort to identify the dominant ES per location before formulating management strategies. We effectively identified 12 ES priorities to best represent conservation target goals for the ES indicators. These 12 priorities had a total areal coverage of 13,364 km2 representing 25.16% of the study area. The 12 priorities were further clustered into five significantly different groups (p-values between groups < 0.05), which helped to refine management strategies formulated to best enhance ES across the study area. The proposed method allows conservation and management plans to easily adapt to a wide variety of quantitative ES target goals within urban and agricultural areas, thereby preventing urban and agriculture sprawl and guiding sustainable urban development. PMID:29682412

  16. A strategy for advancing tilt-rotor technology

    NASA Technical Reports Server (NTRS)

    Morlok, Edward K.; Schoendorfer, David L.

    1985-01-01

    Tilt-rotor technology has many features which make it a very promising development in aviation which might have application to a wide variety of transportation and logistics situations. However, aside from military applications and rather specialized industrial applications, little is known regarding the potential of tilt-rotor for commercial transportation and hence it is difficult to plan a development program which would gain support and be likely to produce a stream of significant benefits. The purpose is to attempt to provide some of this information in a manner that would be useful for preparing a strategy for development of tilt-rotor aircraft technology. Specifically, the objectives were: to identify promising paths of development and deployment of tilt-rotor aircraft technology in the air transportation system considering both benefits and disbenefits, and to identify any particular groups that are likely to benefit significantly and propose plans for gaining their support of research and development of this technology. Potential advantages of the tilt-rotor technology in the context of air transportation as a door-to-door system were identified, and then promising paths of development of such tilt-rotor systems were analyzed. These then lead to recommendations for specific studies, information dissemination and development of awareness of the tilt-rotor among specific transport-related groups.

  17. The use of concept mapping to identify community-driven intervention strategies for physical and mental health.

    PubMed

    Vaughn, Lisa M; Jacquez, Farrah; McLinden, Daniel

    2013-09-01

    Research that partners with youth and community stakeholders increases contextual relevance and community buy-in and therefore maximizes the chance for intervention success. Concept mapping is a mixed-method participatory research process that accesses the input of the community in a collaborative manner. After a school-wide health needs assessment at a low-income, minority/immigrant K-8 school identified bullying and obesity as the most important health issues, concept mapping was used to identify and prioritize specific strategies to address these two areas. Stakeholders including 160 K-8 students, 33 college students working in the school, 35 parents, 20 academic partners, and 22 teachers/staff brainstormed strategies to reduce and prevent obesity and bullying. A smaller group of stakeholders worked individually to complete an unstructured sorting of these strategies into groups of similar ideas, once for obesity and again for bullying. Multidimensional scaling and cluster analysis was applied to the sorting data to produce a series of maps that illustrated the stakeholders' conceptual thinking about obesity and bullying prevention strategies. The maps for both obesity and bullying organized specific strategies into themes that included education, parental role, teacher/school supervision, youth role, expert/professional role, and school structure/support.

  18. Strategies and Models for Promoting Adolescent Vaccination for Low-Income Populations

    ERIC Educational Resources Information Center

    Harris, Katherine M.; Martin, Laurie T.; Lurie, Nicole

    2009-01-01

    In 2007, Sanofi Pasteur asked RAND Health, a division of the RAND Corporation, to study the current climate for adolescent immunization in the United States, to recommend broad strategies for immunizing low-income adolescents (through age 18), and to identify promising "on the ground" practices consistent with the proposed strategic…

  19. Efficiency, equity and feasibility of strategies to identify the poor: an application to premium exemptions under National Health Insurance in Ghana.

    PubMed

    Jehu-Appiah, Caroline; Aryeetey, Genevieve; Spaan, Ernst; Agyepong, Irene; Baltussen, Rob

    2010-05-01

    This paper outlines the potential strategies to identify the poor, and assesses their feasibility, efficiency and equity. Analyses are illustrated for the case of premium exemptions under National Health Insurance (NHI) in Ghana. A literature search in Medline search was performed to identify strategies to identify the poor. Models were developed including information on demography and poverty, and costs and errors of in- and exclusion of these strategies in two regions in Ghana. Proxy means testing (PMT), participatory welfare ranking (PWR), and geographic targeting (GT) are potentially useful strategies to identify the poor, and vary in terms of their efficiency, equity and feasibility. Costs to exempt one poor individual range between US$11.63 and US$66.67, and strategies may exclude up to 25% of the poor. Feasibility of strategies is dependent on their aptness in rural/urban settings, and administrative capacity to implement. A decision framework summarizes the above information to guide policy making. We recommend PMT as an optimal strategy in relative low poverty incidence urbanized settings, PWR as an optimal strategy in relative low poverty incidence rural settings, and GT as an optimal strategy in high incidence poverty settings. This paper holds important lessons not only for NHI in Ghana but also for other countries implementing exemption policies. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  20. Promises, promises for neuroscience and law.

    PubMed

    Buckholtz, Joshua W; Faigman, David L

    2014-09-22

    Stunning technical advances in the ability to image the human brain have provoked excited speculation about the application of neuroscience to other fields. The 'promise' of neuroscience for law has been touted with particular enthusiasm. Here, we contend that this promise elides fundamental conceptual issues that limit the usefulness of neuroscience for law. Recommendations for overcoming these challenges are offered. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. 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.

  2. Video Self-Modeling: A Promising Strategy for Noncompliant Children.

    PubMed

    Axelrod, Michael I; Bellini, Scott; Markoff, Kimberly

    2014-07-01

    The current study investigated the effects of a Video Self-Modeling (VSM) intervention on the compliance and aggressive behavior of three children placed in a psychiatric hospital. Each participant viewed brief video clips of himself following simple adult instructions just prior to the school's morning session and the unit's afternoon free period. A multiple baseline design across settings was used to evaluate the effects of the VSM intervention on compliance with staff instructions and aggressive behavior on the hospital unit and in the hospital-based classroom. All three participants exhibited higher levels of compliance and fewer aggressive episodes during the intervention condition, and the effects were generally maintained when the intervention was withdrawn. Hospital staff reported at the conclusion of the study that the VSM intervention was easy to implement and beneficial for all participants. Taken altogether, the results suggest VSM is a promising, socially acceptable, and proactive intervention approach for improving the behavior of noncompliant children. © The Author(s) 2014.

  3. Mesenchymal stem cell-derived microparticles: a promising therapeutic strategy.

    PubMed

    Tan, Xi; Gong, Yong-Zhen; Wu, Ping; Liao, Duan-Fang; Zheng, Xi-Long

    2014-08-18

    Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on injured and cancerous tissues, MSCs are of great potential in regenerative medicine. MSCs also contribute to reparative processes in different pathological conditions, including cardiovascular diseases and cancer. However, many studies have shown that only a small proportion of transplanted MSCs can actually survive and be incorporated into host tissues. The effects of MSCs cannot be fully explained by their number. Recent discoveries suggest that microparticles (MPs) derived from MSCs may be important for the physiological functions of their parent. Though the physiological role of MSC-MPs is currently not well understood, inspiring results indicate that, in tissue repair and anti-cancer therapy, MSC-MPs have similar pro-regenerative and protective properties as their cellular counterparts. Thus, MSC-MPs represent a promising approach that may overcome the obstacles and risks associated with the use of native or engineered MSCs.

  4. Targeting Alcohol Misuse: A Promising Strategy for Reducing Military Sexual Assaults?

    DTIC Science & Technology

    2014-01-01

    unit” (Barlas et al., 2013). In addition, alcoholic beverages are available at military installations at reduced prices (DoDI 1330.09), which is worth...Vol. 39, No. 1994, pp. 99–112. Wagenaar, Alexander C., Matthew J. Salois, and Kelli A. Komro, “Effects of Beverage Alcohol Price and Tax Levels on...consideration of policies to reduce alcohol misuse as a part of a strategy to prevent sexual assaults as well as a broader strategy to address alcohol use

  5. Keeping Promises

    NASA Technical Reports Server (NTRS)

    Howell, Gregory A.

    2005-01-01

    Commitments are between people, not schedules. Project management as practiced today creates a "commitment-free zone," because it assumes that people will commit to centrally managed schedules without providing a mechanism to ensure their work can be done. So they give it their best, but something always seems to come up ..."I tried, but you know how it is." This form of project management does not provide a mechanism to ensure that what should be done, can in fact be done at the required moment. Too often, promises reliable promise. made in coordination meetings are conditional and unreliable. It has been my experience that at times trust can be low and hard to build in this environment. The absence of reliable promises explains why on well-run projects, people are often only completing 30-50 percent of the deliverables they d promised for the week. We all know what a promise is; we have plenty of experience making them and receiving them from others. So what s the problem? The sad fact is that the project environment-like many other work environments- is often so filled with systemic dishonesty, that we don t expect promises that are reliable. Project managers excel when they manage their projects as networks of commitments and help their people learn to elicit and make reliable promises.

  6. The comparison of the performance of two screening strategies identifying newly-diagnosed HIV during pregnancy.

    PubMed

    Boer, Kees; Smit, Colette; van der Flier, Michiel; de Wolf, Frank

    2011-10-01

    In the Netherlands, a non-selective opt-out instead of a selective opt-in antenatal HIV screening strategy was implemented in 2004. In case of infection, screening was followed by prevention of mother-to-child-transmission (PMTCT). We compared the performance of the two strategies in terms of detection of new cases of HIV and vertical transmission. HIV-infected pregnant women were identified retrospectively from the Dutch HIV cohort ATHENA January 2000 to January 2008. Apart from demographic, virological and immunological data, the date of HIV infection in relation to the index pregnancy was established. Separately, all infants diagnosed with HIV born following implementation of the screening program were identified by a questionnaire via the paediatric HIV centres. 162/481 (33.7%) HIV-positive pregnant women were diagnosed with HIV before 2004 and 172/214 (80.3%) after January 2004. Multivariate analysis showed an 8-fold (95% confidence interval 5.47-11.87) increase in the odds of HIV detection during pregnancy after the national introduction of the opt-out strategy. Still, three children born during a 5-year period after July 2004 were infected due to de novo infection in pregnancy. Implementation of a nation-wide screening strategy based upon non-selective opt-out screening followed by effective PMTCT appeared to detect more HIV-infected women for the first time in pregnancy and to reduce vertical transmission of HIV substantially. Nonetheless, still few children are infected because of maternal infection after the first trimester. We propose the introduction of partner screening on HIV as part of the antenatal screening strategy.

  7. Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies.

    PubMed

    Rivera, José Carlos; Holm, Mari; Austeng, Dordi; Morken, Tora Sund; Zhou, Tianwei Ellen; Beaudry-Richard, Alexandra; Sierra, Estefania Marin; Dammann, Olaf; Chemtob, Sylvain

    2017-08-22

    Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

  8. 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…

  9. Mesenchymal Stem Cell-Derived Microparticles: A Promising Therapeutic Strategy

    PubMed Central

    Tan, Xi; Gong, Yong-Zhen; Wu, Ping; Liao, Duan-Fang; Zheng, Xi-Long

    2014-01-01

    Mesenchymal stem cells (MSCs) are multipotent stem cells that give rise to various cell types of the mesodermal germ layer. Because of their unique ability to home in on injured and cancerous tissues, MSCs are of great potential in regenerative medicine. MSCs also contribute to reparative processes in different pathological conditions, including cardiovascular diseases and cancer. However, many studies have shown that only a small proportion of transplanted MSCs can actually survive and be incorporated into host tissues. The effects of MSCs cannot be fully explained by their number. Recent discoveries suggest that microparticles (MPs) derived from MSCs may be important for the physiological functions of their parent. Though the physiological role of MSC-MPs is currently not well understood, inspiring results indicate that, in tissue repair and anti-cancer therapy, MSC-MPs have similar pro-regenerative and protective properties as their cellular counterparts. Thus, MSC-MPs represent a promising approach that may overcome the obstacles and risks associated with the use of native or engineered MSCs. PMID:25196436

  10. Landslides in Equatorial Africa: Identifying culturally, technically and economically feasible resilience strategies

    NASA Astrophysics Data System (ADS)

    Kervyn, Matthieu; de Hontheim, Astrid; Dewitte, Olivier; Jacobs, Liesbet; Maes, Jan; Mertens, Kewan; Trefois, Philippe; Vranken, Liesbet; Poesen, Jean

    2014-05-01

    Landslides (LS) cause significant impacts in many equatorial regions. Their impact depends on their size and speed, the elements at risk and the vulnerability of these elements. This problem is particularly acute in Equatorial Africa characterized by mountainous topography, intense rains, deep weathering profiles, high population density and high vulnerability to geohazards. Every year LS cause fatalities and result in structural and functional damage to infrastructure and properties. Losses from LS are expected to increase in the future in response to the demographic pressure causing more development in landslide-prone areas (LSPA), deforestation and associated changes in land use and land cover, and the changing climate causing higher or more intense rainfalls. Many studies investigated how natural factors and human activities control the occurrence or re-activation of LS. These studies typically delivered susceptibility maps but these are insufficient to lead to efficient risk management. Building resilience requires to have a true hazard estimate, accounting not only for the spatial distribution of future LS but also for their temporal occurrence and the hazard intensity, to quantitatively analyse the socio-economic consequences of LS and to identify effective resilience strategies that are cost-effective, technically efficient and that are culturally acceptable and adapted to the livelihoods of the vulnerable population. Such an analysis is crucial as it enables to provide practical recommendations for households and policy makers to mitigate LS-related damages. This project focuses on 4 representative study areas known for having suffered severely from rainfall-triggered LS in Uganda (Mount Elgon, Mount Rwenzori) and SW and NW Cameroon (Mount Cameroon, Bamenda). In two of these regions, some preliminary studies on LS characteristics and susceptibility mapping have been carried out, while hazard maps, a socio-economic impact analysis and resilience strategies

  11. Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections.

    PubMed

    Don, Rob; Ioset, Jean-Robert

    2014-01-01

    The Drugs for Neglected Diseases initiative (DNDi) has defined and implemented an early discovery strategy over the last few years, in fitting with its virtual R&D business model. This strategy relies on a medium- to high-throughput phenotypic assay platform to expedite the screening of compound libraries accessed through its collaborations with partners from the pharmaceutical industry. We review the pragmatic approaches used to select compound libraries for screening against kinetoplastids, taking into account screening capacity. The advantages, limitations and current achievements in identifying new quality series for further development into preclinical candidates are critically discussed, together with attractive new approaches currently under investigation.

  12. Stakeholders' participatory diagnosis of climate change impacts on subsistence agriculture in Sikkim, India, for identifying adaptation strategies

    NASA Astrophysics Data System (ADS)

    Azhoni, A.; Goyal, M. K.

    2017-12-01

    Narrowing the gap between research, policy making and implementing adaptation remains a challenge in many parts of the world where climate change is likely to severely impact subsistence agriculture. This research aims to narrow this gap by matching the adaptation strategies being framed by policy makers and perspectives of consultants and researchers which are expected to be implemented by development agencies farmers in the state of Sikkim in India. Our case study examined the framing and implementation of State Action Plan on Climate Change through semi-structured interviews carried out with decision makers in the State Government, Scientific Organisations, consultants, local academia, implementing and development agencies, and farmers for whom the adaptation strategies are targeted. Using Social Network and Stakeholder Analysis approach, this research unravels the complexities of perceiving climate change impacts, identifying adaptation strategies, and implementing climate change adaptation strategies. While farmers are less aware about the global phenomenon of climate change impacts for their subsistence livelihood, their knowledge of the local conditions and their close interaction with the State Government Agriculture Department provides them an access to new and high value crops. Although important steps are initiated through the Sikkim State Action Plan on Climate Change it is yet to deliver effective means of adaptation implementation and identifying the networks of close coordination between the various implementing agencies will likely to pay rich dividends. While Sikkim being a small and hilly state with specific contextual challenges of climate change impacts, the results from this study highlights how the internal and external networks between various types of stakeholders informs decision makers in identifying local impacts of climate change and plan adaptation strategies.

  13. Integrative strategies to identify candidate genes in rodent models of human alcoholism.

    PubMed

    Treadwell, Julie A

    2006-01-01

    The search for genes underlying alcohol-related behaviours in rodent models of human alcoholism has been ongoing for many years with only limited success. Recently, new strategies that integrate several of the traditional approaches have provided new insights into the molecular mechanisms underlying ethanol's actions in the brain. We have used alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) genetic strains of mice in an integrative strategy combining high-throughput gene expression screening, genetic segregation analysis, and mapping to previously published quantitative trait loci to uncover candidate genes for the ethanol-preference phenotype. In our study, 2 genes, retinaldehyde binding protein 1 (Rlbp1) and syntaxin 12 (Stx12), were found to be strong candidates for ethanol preference. Such experimental approaches have the power and the potential to greatly speed up the laborious process of identifying candidate genes for the animal models of human alcoholism.

  14. Stakeholders identify similar barriers but different strategies to facilitate return-to-work: A vignette of a worker with an upper extremity condition.

    PubMed

    Peters, Susan E; Truong, Anthony P; Johnston, Venerina

    2018-01-01

    Stakeholders involved in the return-to-work (RTW) process have different roles and qualificationsOBJECTIVE:To explore the perspectives of Australian stakeholders of the RTW barriers and strategies for a worker with an upper extremity condition and a complex workers' compensation case. Using a case vignette, stakeholders were asked to identify barriers and recommend strategies to facilitate RTW. Content analysis was performed on the open-ended responses. The responses were categorised into RTW barriers and strategies using the biopsychosocial model. Pearson's Chi Square and ANOVA were performed to establish group differences. 621 participants (488 healthcare providers (HCPs), 62 employers, 55 insurers and 16 lawyers) identified 36 barriers (31 modifiable): 4 demographic; 8 biological; 15 psychological and 9 social barriers. 484 participants reported 16 RTW strategies: 4 biological; 6 psychological and 6 social strategies. 'Work relationship stressors' (83.4%) and 'Personal relationship stressors' (64.7%) were the most frequently nominated barriers. HCPs most frequently nominated 'Pain management' (49.6%), while employers, insurers and lawyers nominated 'RTW planning/Suitable duties programs' (40.5%; 42.9%; 80%). Stakeholders perceived similar barriers for RTW but recommended different strategies. Stakeholders appeared to be more proficient in identifying barriers than recommending strategies. Future research should focus on tools to both identify RTW barriers and direct intervention.

  15. The quality of clinical maternal and neonatal healthcare - a strategy for identifying 'routine care signal functions'.

    PubMed

    Brenner, Stephan; De Allegri, Manuela; Gabrysch, Sabine; Chinkhumba, Jobiba; Sarker, Malabika; Muula, Adamson S

    2015-01-01

    A variety of clinical process indicators exists to measure the quality of care provided by maternal and neonatal health (MNH) programs. To allow comparison across MNH programs in low- and middle-income countries (LMICs), a core set of essential process indicators is needed. Although such a core set is available for emergency obstetric care (EmOC), the 'EmOC signal functions', a similar approach is currently missing for MNH routine care evaluation. We describe a strategy for identifying core process indicators for routine care and illustrate their usefulness in a field example. We first developed an indicator selection strategy by combining epidemiological and programmatic aspects relevant to MNH in LMICs. We then identified routine care process indicators meeting our selection criteria by reviewing existing quality of care assessment protocols. We grouped these indicators into three categories based on their main function in addressing risk factors of maternal or neonatal complications. We then tested this indicator set in a study assessing MNH quality of clinical care in 33 health facilities in Malawi. Our strategy identified 51 routine care processes: 23 related to initial patient risk assessment, 17 to risk monitoring, 11 to risk prevention. During the clinical performance assessment a total of 82 cases were observed. Birth attendants' adherence to clinical standards was lowest in relation to risk monitoring processes. In relation to major complications, routine care processes addressing fetal and newborn distress were performed relatively consistently, but there were major gaps in the performance of routine care processes addressing bleeding, infection, and pre-eclampsia risks. The identified set of process indicators could identify major gaps in the quality of obstetric and neonatal care provided during the intra- and immediate postpartum period. We hope our suggested indicators for essential routine care processes will contribute to streamlining MNH program

  16. Identifying nurse staffing research in Medline: development and testing of empirically derived search strategies with the PubMed interface

    PubMed Central

    2010-01-01

    Background The identification of health services research in databases such as PubMed/Medline is a cumbersome task. This task becomes even more difficult if the field of interest involves the use of diverse methods and data sources, as is the case with nurse staffing research. This type of research investigates the association between nurse staffing parameters and nursing and patient outcomes. A comprehensively developed search strategy may help identify nurse staffing research in PubMed/Medline. Methods A set of relevant references in PubMed/Medline was identified by means of three systematic reviews. This development set was used to detect candidate free-text and MeSH terms. The frequency of these terms was compared to a random sample from PubMed/Medline in order to identify terms specific to nurse staffing research, which were then used to develop a sensitive, precise and balanced search strategy. To determine their precision, the newly developed search strategies were tested against a) the pool of relevant references extracted from the systematic reviews, b) a reference set identified from an electronic journal screening, and c) a sample from PubMed/Medline. Finally, all newly developed strategies were compared to PubMed's Health Services Research Queries (PubMed's HSR Queries). Results The sensitivities of the newly developed search strategies were almost 100% in all of the three test sets applied; precision ranged from 6.1% to 32.0%. PubMed's HSR queries were less sensitive (83.3% to 88.2%) than the new search strategies. Only minor differences in precision were found (5.0% to 32.0%). Conclusions As with other literature on health services research, nurse staffing studies are difficult to identify in PubMed/Medline. Depending on the purpose of the search, researchers can choose between high sensitivity and retrieval of a large number of references or high precision, i.e. and an increased risk of missing relevant references, respectively. More standardized

  17. Identifying nurse staffing research in Medline: development and testing of empirically derived search strategies with the PubMed interface.

    PubMed

    Simon, Michael; Hausner, Elke; Klaus, Susan F; Dunton, Nancy E

    2010-08-23

    The identification of health services research in databases such as PubMed/Medline is a cumbersome task. This task becomes even more difficult if the field of interest involves the use of diverse methods and data sources, as is the case with nurse staffing research. This type of research investigates the association between nurse staffing parameters and nursing and patient outcomes. A comprehensively developed search strategy may help identify nurse staffing research in PubMed/Medline. A set of relevant references in PubMed/Medline was identified by means of three systematic reviews. This development set was used to detect candidate free-text and MeSH terms. The frequency of these terms was compared to a random sample from PubMed/Medline in order to identify terms specific to nurse staffing research, which were then used to develop a sensitive, precise and balanced search strategy. To determine their precision, the newly developed search strategies were tested against a) the pool of relevant references extracted from the systematic reviews, b) a reference set identified from an electronic journal screening, and c) a sample from PubMed/Medline. Finally, all newly developed strategies were compared to PubMed's Health Services Research Queries (PubMed's HSR Queries). The sensitivities of the newly developed search strategies were almost 100% in all of the three test sets applied; precision ranged from 6.1% to 32.0%. PubMed's HSR queries were less sensitive (83.3% to 88.2%) than the new search strategies. Only minor differences in precision were found (5.0% to 32.0%). As with other literature on health services research, nurse staffing studies are difficult to identify in PubMed/Medline. Depending on the purpose of the search, researchers can choose between high sensitivity and retrieval of a large number of references or high precision, i.e. and an increased risk of missing relevant references, respectively. More standardized terminology (e.g. by consistent use of the

  18. 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

  19. Identifying and ranking implicit leadership strategies to promote evidence-based practice implementation in addiction health services.

    PubMed

    Guerrero, Erick G; Padwa, Howard; Fenwick, Karissa; Harris, Lesley M; Aarons, Gregory A

    2016-05-14

    Despite a solid research base supporting evidence-based practices (EBPs) for addiction treatment such as contingency management and medication-assisted treatment, these services are rarely implemented and delivered in community-based addiction treatment programs in the USA. As a result, many clients do not benefit from the most current and efficacious treatments, resulting in reduced quality of care and compromised treatment outcomes. Previous research indicates that addiction program leaders play a key role in supporting EBP adoption and use. The present study expanded on this previous work to identify strategies that addiction treatment program leaders report using to implement new practices. We relied on a staged and iterative mixed-methods approach to achieve the following four goals: (a) collect data using focus groups and semistructured interviews and conduct analyses to identify implicit managerial strategies for implementation, (b) use surveys to quantitatively rank strategy effectiveness, (c) determine how strategies fit with existing theories of organizational management and change, and (d) use a consensus group to corroborate and expand on the results of the previous three stages. Each goal corresponded to a methodological phase, which included data collection and analytic approaches to identify and evaluate leadership interventions that facilitate EBP implementation in community-based addiction treatment programs. Findings show that the top-ranked strategies involved the recruitment and selection of staff members receptive to change, offering support and requesting feedback during the implementation process, and offering in vivo and hands-on training. Most strategies corresponded to emergent implementation leadership approaches that also utilize principles of transformational and transactional leadership styles. Leadership behaviors represented orientations such as being proactive to respond to implementation needs, supportive to assist staff members

  20. 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

  1. 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.

  2. Identifying Service Delivery Strategies for Ethnically Diverse Users of a Wildland-Urban Recreation Site

    Treesearch

    John M. Baas

    1992-01-01

    Service delivery has become an increasingly important part of managing public lands for recreation. The range of preferences held by ethnically diverse users of recreation sites may warrant the development of more than one service delivery strategy. Two questions were examined: (1) Are there differences in site perceptions that can be identified on the basis on...

  3. Search strategies to identify information on adverse effects: a systematic review

    PubMed Central

    Golder, Su; Loke, Yoon

    2009-01-01

    Objectives: The review evaluated studies of electronic database search strategies designed to retrieve adverse effects data for systematic reviews. Methods: Studies of adverse effects were located in ten databases as well as by checking references, hand-searching, searching citations, and contacting experts. Two reviewers screened the retrieved records for potentially relevant papers. Results: Five thousand three hundred thirteen citations were retrieved, yielding 19 studies designed to develop or evaluate adverse effect filters, of which 3 met the inclusion criteria. All 3 studies identified highly sensitive search strategies capable of retrieving over 95% of relevant records. However, 1 study did not evaluate precision, while the level of precision in the other 2 studies ranged from 0.8% to 2.8%. Methodological issues in these papers included the relatively small number of records, absence of a validation set of records for testing, and limited evaluation of precision. Conclusions: The results indicate the difficulty of achieving highly sensitive searches for information on adverse effects with a reasonable level of precision. Researchers who intend to locate studies on adverse effects should allow for the amount of resources and time required to conduct a highly sensitive search. PMID:19404498

  4. 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.

  5. User-identified electronic cigarette behavioral strategies and device characteristics for cigarette smoking reduction.

    PubMed

    Soule, Eric K; Maloney, Sarah F; Guy, Mignonne C; Eissenberg, Thomas; Fagan, Pebbles

    2018-04-01

    There is limited evidence on how cigarette smokers use electronic cigarettes (ECIGs) for smoking cessation and reduction. This study used concept mapping, a participatory mixed-methods research approach, to identify ECIG use behaviors and device characteristics perceived to be associated with cigarette smoking cessation or reduction. Current ECIG users aged 18-64 were recruited from seven cities selected randomly from U.S. census tract regions. Participants were invited to complete concept mapping tasks: brainstorming, sorting and rating (n=72). During brainstorming, participants generated statements in response to a focus prompt ("A SPECIFIC WAY I HAVE USED electronic cigarettes to reduce my cigarette smoking or a SPECIFIC WAY electronic cigarettes help me reduce my cigarette smoking is…") and then sorted and rated the statements. Multidimensional scaling and hierarchical cluster analyses were used to generate a cluster map that was interpreted by the research team. Eight thematic clusters were identified: Convenience, Perceived Health Effects, Ease of Use, Versatility and Variety, Advantages of ECIGs over Cigarettes, Cigarette Substitutability, Reducing Harms to Self and Others, and Social Benefits. Participants generated several statements that related to specific behavioral strategies used when using ECIGs for smoking reduction/complete switching behaviors such as making rapid transitions from smoking to ECIG use or using certain ECIG liquids or devices. Former smokers rated the Perceived Health Effects cluster and several behavioral strategy statements higher than current smokers. These results help to identify ECIG use behaviors and characteristics perceived by ECIG users to aid in cigarette smoking cessation or reduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Mini-ISES identifies promising carbafructopyranose-based salens for asymmetric catalysis: Tuning ligand shape via the anomeric effect

    PubMed Central

    Karukurichi, Kannan R.; Fei, Xiang; Swyka, Robert A.; Broussy, Sylvain; Shen, Weijun; Dey, Sangeeta; Roy, Sandip K.; Berkowitz, David B.

    2015-01-01

    This study introduces new methods of screening for and tuning chiral space and in so doing identifies a promising set of chiral ligands for asymmetric synthesis. The carbafructopyranosyl-1,2-diamine(s) and salens constructed therefrom are particularly compelling. It is shown that by removing the native anomeric effect in this ligand family, one can tune chiral ligand shape and improve chiral bias. This concept is demonstrated by a combination of (i) x-ray crystallographic structure determination, (ii) assessment of catalytic performance, and (iii) consideration of the anomeric effect and its underlying dipolar basis. The title ligands were identified by a new mini version of the in situ enzymatic screening (ISES) procedure through which catalyst-ligand combinations are screened in parallel, and information on relative rate and enantioselectivity is obtained in real time, without the need to quench reactions or draw aliquots. Mini-ISES brings the technique into the nanomole regime (200 to 350 nmol catalyst/20 μl organic volume) commensurate with emerging trends in reaction development/process chemistry. The best-performing β-d-carbafructopyranosyl-1,2-diamine–derived salen ligand discovered here outperforms the best known organometallic and enzymatic catalysts for the hydrolytic kinetic resolution of 3-phenylpropylene oxide, one of several substrates examined for which the ligand is “matched.” This ligand scaffold defines a new swath of chiral space, and anomeric effect tunability defines a new concept in shaping that chiral space. Both this ligand set and the anomeric shape-tuning concept are expected to find broad application, given the value of chiral 1,2-diamines and salens constructed from these in asymmetric catalysis. PMID:26501130

  7. The Fire Learning Network: A promising conservation strategy for forestry

    Treesearch

    Bruce E. Goldstein; William H. Butler; R. Bruce Hull

    2010-01-01

    Conservation Learning Networks (CLN) are an emerging conservation strategy for addressing complex resource management challenges that face the forestry profession. The US Fire Learning Network (FLN) is a successful example of a CLN that operates on a national scale. Developed in 2001 as a partnership between The Nature Conservancy, the US Forest Service, and land-...

  8. Reducing the Risk, Increasing the Promise: Strategies for Student Success

    ERIC Educational Resources Information Center

    Bergmann, Sherrel; Brough, Judith Allen

    2012-01-01

    In their new book, Bergmann and Brough provide a clear path to follow for helping your at-risk students achieve success in and out of the classroom. Packed with classroom-tested, practical strategies and lesson plans for teaching respect, responsibility, resilience, reading, and other essential skills to at-risk students, this is a must-have book…

  9. Cannabidiol as a Promising Strategy to Treat and Prevent Movement Disorders?

    PubMed Central

    Peres, Fernanda F.; Lima, Alvaro C.; Hallak, Jaime E. C.; Crippa, José A.; Silva, Regina H.; Abílio, Vanessa C.

    2018-01-01

    Movement disorders such as Parkinson's disease and dyskinesia are highly debilitating conditions linked to oxidative stress and neurodegeneration. When available, the pharmacological therapies for these disorders are still mainly symptomatic, do not benefit all patients and induce severe side effects. Cannabidiol is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects. Although the studies that investigate the effects of this compound on movement disorders are surprisingly few, cannabidiol emerges as a promising compound to treat and/or prevent them. Here, we review these clinical and pre-clinical studies and draw attention to the potential of cannabidiol in this field. PMID:29867488

  10. 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…

  11. 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

  12. Root Cause Analyses of Suicides of Mental Health Clients: Identifying Systematic Processes and Service-Level Prevention Strategies.

    PubMed

    Gillies, Donna; Chicop, David; O'Halloran, Paul

    2015-01-01

    The ability to predict imminent risk of suicide is limited, particularly among mental health clients. Root cause analysis (RCA) can be used by health services to identify service-wide approaches to suicide prevention. To (a) develop a standardized taxonomy for RCAs; (b) to quantitate service-related factors associated with suicides; and (c) to identify service-related suicide prevention strategies. The RCAs of all people who died by suicide within 1 week of contact with the mental health service over 5 years were thematically analyzed using a data collection tool. Data were derived from RCAs of all 64 people who died by suicide between 2008 and 2012. Major themes were categorized as individual, situational, and care-related factors. The most common factor was that clients had recently denied suicidality. Reliance on carers, recent changes in medication, communication problems, and problems in follow-through were also commonly identified. Given the difficulty in predicting suicide in people whose expressions of suicidal ideation change so rapidly, services may consider the use of strategies aimed at improving the individual, stressor, support, and care factors identified in this study.

  13. Workplace-Based Assessment: A Review of User Perceptions and Strategies to Address the Identified Shortcomings

    ERIC Educational Resources Information Center

    Massie, Jonathan; Ali, Jason M.

    2016-01-01

    Workplace based assessments (WBAs) are now commonplace in postgraduate medical training. User acceptability and engagement is essential to the success of any medical education innovation. To this end, possessing an insight into trainee and trainer perceptions towards WBAs will help identify the major problems, permitting strategies to be…

  14. Profiles of Selected Promising Professional Development Initiatives.

    ERIC Educational Resources Information Center

    Cohen, Carol; Gerber, Peter; Handley, Claire; Kronley, Robert; Parry, Megan

    In 2000, the Finance Project received a planning grant to launch a new initiative on financing professional development in education. This report represents efforts to identify and develop a database on promising new approaches to professional development in education, profiling 16 initiatives recommended by knowledge experts and representing a…

  15. Realising the Promise of Cancer Predisposition Genes

    PubMed Central

    Rahman, Nazneen

    2016-01-01

    Genes in which germline mutations confer high or moderate increased risks of cancer are called cancer predisposition genes (CPG). Over 100 CPGs have been identified providing important scientific insights in many areas, particularly mechanisms of cancer causation. Moreover, clinical utilisation of CPGs has had substantial impact in diagnosis, optimised management and prevention of cancer. The recent transformative advances in DNA sequencing bring the promise of many more CPG discoveries and greater, broader clinical applications. However, there is also considerable potential for incorrect inferences and inappropriate clinical applications. Realising the promise of cancer predisposition genes for science and medicine will thus require careful navigation. PMID:24429628

  16. Identifying and Evaluating the Therapeutic Strategies Used During a Manualized Self- Advocacy Intervention for Transition-Age Youth.

    PubMed

    Kramer, Jessica M

    2015-01-01

    Prior to undertaking randomized control trials, pilot research should ensure that an intervention's active ingredients are operationalized in manuals or protocols. This study identified the strategies facilitators reported to use during the implementation of a problem-solving self-advocacy intervention, Project "Teens making Environment and Activity Modifications" (TEAM), with transition-age youth with developmental disabilities, and evaluated the alignment of strategies with the intervention's hypothesized mechanisms of change. An iterative process was used to conduct a content analysis of 106 field notes completed by six facilitators. Facilitators used 19 strategies. Findings suggest that facilitators used strategies simultaneously to ensure universal design for learning, maximize relevance for individual trainees, and maintain a safe and encouraging environment. Facilitators can individualize Project TEAM in a way that operationalizes the mechanisms of change underlying Project TEAM. The quality of the intervention may improve by explicitly incorporating these strategies into the intervention protocol. The strategies may also be applicable to therapists implementing interventions informed, by similar theoretical propositions.

  17. Identifying additional studies for a systematic review of retention strategies in randomised controlled trials: making contact with trials units and trial methodologists.

    PubMed

    Brueton, Valerie; Tierney, Jayne F; Stenning, Sally; Rait, Greta

    2017-08-22

    Search strategies for systematic reviews aim to identify all evidence relevant to the research question posed. Reports of methodological research can be difficult to find leading to biased results in systematic reviews of research methodology. Evidence suggests that contact with investigators can help to identify unpublished research. To identify additional eligible randomised controlled trials (RCTs) for a Cochrane systematic review of strategies to improve retention in RCTs, we conducted a survey of UK clinical trials units (CTUs) and made contact with RCT methodologists. Key contacts for all UK CTUs were sent a personalised email with a short questionnaire and summary protocol of the Cochrane methodology review. The questionnaire asked whether a RCT evaluating strategies to improve retention embedded in a RCT had ever been conducted by the CTU. Questions about the stage of completion and publication of such RCTs were included. The summary protocol outlined the aims, eligibility criteria, examples of types of retention strategies, and the primary outcome for the systematic review. Personal communication with RCT methodologists and presentations of preliminary results of the review at conferences were also used to identify additional eligible RCTs. We checked the results of our standard searches to see if eligible studies identified through these additional methods were also found using our standard searches. We identified 14 of the 38 RCTs included in the Cochrane methodology review by contacting trials units and methodologists. Eleven of the 14 RCTs identified by these methods were either published in grey literature, in press or unpublished. Three remaining RCTs were fully published at the time. Six of the RCTs identified were not found through any other searches. The RCTs identified represented data for 6 of 14 RCTs of incentive strategies (52% of randomised participants included in the review), and 6 of 14 RCTs of communication strategies (52% of randomised

  18. Identifying multi-level culturally appropriate smoking cessation strategies for Aboriginal health staff: a concept mapping approach.

    PubMed

    Dawson, Anna P; Cargo, Margaret; Stewart, Harold; Chong, Alwin; Daniel, Mark

    2013-02-01

    Aboriginal Australians, including Aboriginal Health Workers (AHWs), smoke at rates double the non-Aboriginal population. This study utilized concept mapping methodology to identify and prioritize culturally relevant strategies to promote smoking cessation in AHWs. Stakeholder participants included AHWs, other health service employees and tobacco control personnel. Smoking cessation strategies (n = 74) were brainstormed using 34 interviews, 3 focus groups and a stakeholder workshop. Stakeholders sorted strategies into meaningful groups and rated them on perceived importance and feasibility. A concept map was developed using multi-dimensional scaling and hierarchical cluster analyses. Ten unique clusters of smoking cessation strategies were depicted that targeted individuals, family and peers, community, workplace and public policy. Smoking cessation resources and services were represented in addition to broader strategies addressing social and environmental stressors that perpetuate smoking and make quitting difficult. The perceived importance and feasibility of clusters were rated differently by participants working in health services that were government-coordinated compared with community-controlled. For health service workers within vulnerable populations, these findings clearly implicate a need for contextualized strategies that mitigate social and environmental stressors in addition to conventional strategies for tobacco control. The concept map is being applied in knowledge translation to guide development of smoking cessation programs for AHWs.

  19. Nutritional strategies of Latino farmworker families with preschool children: Identifying leverage points for obesity prevention

    PubMed Central

    Quandt, Sara A.; Grzywacz, Joseph G.; Trejo, Grisel; Arcury, Thomas A.

    2014-01-01

    Obesity and overweight are significant problems for children in the US, particularly for Hispanic children. This paper focuses on the children in families of immigrant Hispanic farmworkers, as farm work is the portal though which many immigrants come to the US. This paper (1) describes a model of the nutritional strategies of child feeding in farmworker families; and (2) uses this model to identify leverage points for efforts to improve the nutritional status of these children. In-depth interviews were conducted in Spanish with 33 mothers of 2–5 year old children in farmworker families recruited in North Carolina in 2010–2011. The purposive sample was balanced by farmworker status (migrant or seasonal), child age, and child gender. Interviews were transcribed and translated. Multiple coders and a team approach to analysis were used. Nutritional strategies centered on domains of procuring food, using food, and maintaining food security. The content of these domains reflected environmental factors (e.g., rural isolation, shared housing), contextual factors (e.g., beliefs about appropriate food, parenting style), and available resources (e.g., income, government programs). Environmental isolation and limited access to resources decrease the amount and diversity of household food supplies. Parental actions (parental sacrifices, reduced dietary variety) attempt to buffer children. Use of government food sources is valuable for eligible families. Leverage points are suggested that would change nutritional strategy components and lower the risk of overweight and obesity. Further prospective research is needed to verify the nutritional strategy identified and to test the ability of leverage points to prevent childhood obesity in this vulnerable population. PMID:25462607

  20. 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

  1. Identifying and assessing strategies for evaluating the impact of mobile eye health units on health outcomes.

    PubMed

    Fu, Shiwan; Turner, Angus; Tan, Irene; Muir, Josephine

    2017-12-01

    To identify and assess strategies for evaluating the impact of mobile eye health units on health outcomes. Systematic literature review. Worldwide. Peer-reviewed journal articles that included the use of a mobile eye health unit. Journal articles were included if outcome measures reflected an assessment of the impact of a mobile eye health unit on health outcomes. Six studies were identified with mobile services offering diabetic retinopathy screening (three studies), optometric services (two studies) and orthoptic services (one study). This review identified and assessed strategies in existing literature used to evaluate the impact of mobile eye health units on health outcomes. Studies included in this review used patient outcomes (i.e. disease detection, vision impairment, treatment compliance) and/or service delivery outcomes (i.e. cost per attendance, hospital transport use, inappropriate referrals, time from diabetic retinopathy photography to treatment) to evaluate the impact of mobile eye health units. Limitations include difficulty proving causation of specific outcome measures and the overall shortage of impact evaluation studies. Variation in geographical location, service population and nature of eye care providers limits broad application. © 2017 National Rural Health Alliance Inc.

  2. Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies.

    PubMed

    Doctor, Allan; Zimmerman, Jerry; Agus, Michael; Rajasekaran, Surender; Bubeck Wardenburg, Juliane; Fortenberry, James; Zajicek, Anne; Mairson, Emma; Typpo, Katri

    2017-03-01

    To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). Literature review, research data, and expert opinion. Not applicable. Moderated by an expert from the field, issues relevant to the association of multiple organ dysfunction syndrome with a variety of conditions were presented, discussed, and debated with a focus on identifying knowledge gaps and research priorities. Summary of presentations and discussion supported and supplemented by relevant literature. Among critically ill children, multiple organ dysfunction syndrome is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this article, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of multiple organ dysfunction syndrome. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anticytokine therapies, antitoxin treatments, antioxidant approaches, and multiple forms of exogenous steroids. For the field to advance, promising therapies and other therapies must be assessed in rigorous manner and implemented accordingly.

  3. Identifying Multi-Level Culturally Appropriate Smoking Cessation Strategies for Aboriginal Health Staff: A Concept Mapping Approach

    ERIC Educational Resources Information Center

    Dawson, Anna P.; Cargo, Margaret; Stewart, Harold; Chong, Alwin; Daniel, Mark

    2013-01-01

    Aboriginal Australians, including Aboriginal Health Workers (AHWs), smoke at rates double the non-Aboriginal population. This study utilized concept mapping methodology to identify and prioritize culturally relevant strategies to promote smoking cessation in AHWs. Stakeholder participants included AHWs, other health service employees and tobacco…

  4. 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.

  5. Codemeshing in Academic Writing: Identifying Teachable Strategies of Translanguaging

    ERIC Educational Resources Information Center

    Canagarajah, Suresh

    2011-01-01

    Studies on translanguaging of multilingual students have turned their attention to teachable strategies in classrooms. This study is based on the assumption that it is possible to learn from students' translanguaging strategies while developing their proficiency through a dialogical pedagogy. Based on a classroom ethnography, this article…

  6. Modeling heterogeneity in the pluripotent state: A promising strategy for improving the efficiency and fidelity of stem cell differentiation

    PubMed Central

    Espinosa Angarica, Vladimir

    2016-01-01

    Pluripotency can be considered a functional characteristic of pluripotent stem cells (PSCs) populations and their niches, rather than a property of individual cells. In this view, individual cells within the population independently adopt a variety of different expression states, maintained by different signaling, transcriptional, and epigenetics regulatory networks. In this review, we propose that generation of integrative network models from single cell data will be essential for getting a better understanding of the regulation of self‐renewal and differentiation. In particular, we suggest that the identification of network stability determinants in these integrative models will provide important insights into the mechanisms mediating the transduction of signals from the niche, and how these signals can trigger differentiation. In this regard, the differential use of these stability determinants in subpopulation‐specific regulatory networks would mediate differentiation into different cell fates. We suggest that this approach could offer a promising avenue for the development of novel strategies for increasing the efficiency and fidelity of differentiation, which could have a strong impact on regenerative medicine. PMID:27321053

  7. Housing Matters for Families: Promising Practices from Child Welfare Agencies.

    PubMed

    Cunningham, Mary; Pergamit, Michael

    There is growing acknowledgement that housing can provide more than shelter, a basic need. Housing can also act as a foundation, helping families stay together.The provision of housing as a prevention or protective strategy against child maltreatment has not been widely used by child welfare agencies. A small subset of child welfare agencies across the country, however, is incorporating housing into their response to cases of child abuse and neglect. Using qualitative data from ongoing studies of HUD's Family Unification Program (FUP) and the Children's Bureau supportive housing demonstration for high-need child welfare involved families, we describe some of the promising practices agencies are implementing and testing. Though evaluations of these programs are not yet complete, there is a lot the field can learn from these approaches. This paper provides an overview of seven promising strategies: (1) partnering with public housing agencies and leveraging resources; (2) assessing the housing needs of child welfare involved families; (3) triaging and providing housing resources based on needs; (4) providing housing first, not. last; (5) developing housing stability plans and shared case plans; (6) screening families into housing, rather than screening out; and (7) providing housing search assistance.

  8. Promising Practices in Drug Treatment: Findings from Europe

    ERIC Educational Resources Information Center

    Nemes, Susanna; Libretto, Salvatore; Skinstad, Anne Helene; Garrett, Gerald; Hoffman, Jeffrey A.

    2005-01-01

    In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in four European countries-Poland, Spain, Slovenia, and Italy-were examined to identify promising practices and to assess lessons…

  9. 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.

  10. Intervention Strategies Used in Sport Injury Prevention Studies: A Systematic Review Identifying Studies Applying the Haddon Matrix.

    PubMed

    Vriend, Ingrid; Gouttebarge, Vincent; Finch, Caroline F; van Mechelen, Willem; Verhagen, Evert A L M

    2017-10-01

    Prevention of sport injuries is crucial to maximise the health and societal benefits of a physically active lifestyle. To strengthen the translation and implementation of the available evidence base on effective preventive measures, a range of potentially relevant strategies should be considered. Our aim was to identify and categorise intervention strategies for the prevention of acute sport injuries evaluated in the scientific literature, applying the Haddon matrix, and identify potential knowledge gaps. Five electronic databases were searched (PubMed, EMBASE, SPORTDiscus, CINAHL, Cochrane) for studies that evaluated the effect of interventions on the occurrence of acute sport injuries. Studies were required to include a control group/condition, prospective data collection, and a quantitative injury outcome measure. A total of 155 studies were included, mostly randomised controlled trials (43%). The majority of studies (55%) focussed on strategies requiring a behavioural change on the part of athletes. Studies predominantly evaluated the preventive effect of various training programmes targeted at the 'pre-event' phase (n = 73) and the use of equipment to avoid injury in the 'event phase' (n = 29). A limited number of studies evaluated the preventive effect of strategies geared at rules and regulations (n = 14), and contextual modifications (n = 18). Studies specifically aimed at preventing re-injuries were a minority (n = 8), and were mostly related to ankle sprains (n = 5). Valuable insight into the extent of the evidence base of sport injury prevention studies was obtained for 20 potential intervention strategies. This approach can be used to monitor potential gaps in the knowledge base on sport injury prevention.

  11. Identifying mismatches between institutional perceptions of water-related risk drivers and water management strategies in three river basin areas

    NASA Astrophysics Data System (ADS)

    Räsänen, Aleksi; Juhola, Sirkku; Monge Monge, Adrián; Käkönen, Mira; Kanninen, Markku; Nygren, Anja

    2017-07-01

    Water-related risks and vulnerabilities are driven by variety of stressors, including climate and land use change, as well as changes in socio-economic positions and political landscapes. Hence, water governance, which addresses risks and vulnerabilities, should target multiple stressors. We analyze the institutional perceptions of the drivers and strategies for managing water-related risks and vulnerabilities in three regionally important river basin areas located in Finland, Mexico, and Laos. Our analysis is based on data gathered through participatory workshops and complemented by qualitative content analysis of relevant policy documents. The identified drivers and proposed risk reduction strategies showed the multidimensionality and context-specificity of water-related risks and vulnerabilities across study areas. Most of the identified drivers were seen to increase risks, but some of the drivers were positive trends, and drivers also included also policy instruments that can both increase or decrease risks. Nevertheless, all perceived drivers were not addressed with suggested risk reduction strategies. In particular, most of the risk reduction strategies were incremental adjustments, although many of the drivers classified as most important were large-scale trends, such as climate change, land use changes and increase in foreign investments. We argue that there is a scale mismatch between the identified drivers and suggested strategies, which questions the opportunity to manage the drivers by single-scale incremental adjustments. Our study suggests that for more sustainable risk and vulnerability reduction, the root causes of water-related risks and vulnerabilities should be addressed through adaptive multi-scale governance that carefully considers the context-specificity and the multidimensionality of the associated drivers and stressors.

  12. Do promises matter? An exploration of the role of promises in psychological contract breach.

    PubMed

    Montes, Samantha D; Zweig, David

    2009-09-01

    Promises are positioned centrally in the study of psychological contract breach and are argued to distinguish psychological contracts from related constructs, such as employee expectations. However, because the effects of promises and delivered inducements are confounded in most research, the role of promises in perceptions of, and reactions to, breach remains unclear. If promises are not an important determinant of employee perceptions, emotions, and behavioral intentions, this would suggest that the psychological contract breach construct might lack utility. To assess the unique role of promises, the authors manipulated promises and delivered inducements separately in hypothetical scenarios in Studies 1 (558 undergraduates) and 2 (441 employees), and they measured them separately (longitudinally) in Study 3 (383 employees). The authors' results indicate that breach perceptions do not represent a discrepancy between what employees believe they were promised and were given. In fact, breach perceptions can exist in the absence of promises. Further, promises play a negligible role in predicting feelings of violation and behavioral intentions. Contrary to the extant literature, the authors' findings suggest that promises may matter little; employees are concerned primarily with what the organization delivers.

  13. Identifying optimal postmarket surveillance strategies for medical and surgical devices: implications for policy, practice and research.

    PubMed

    Gagliardi, Anna R; Umoquit, Muriah; Lehoux, Pascale; Ross, Sue; Ducey, Ariel; Urbach, David R

    2013-03-01

    Non-drug technologies offer many benefits, but have been associated with adverse events, prompting calls for improved postmarket surveillance. There is little empirical research to guide the development of such a system. The purpose of this study was to identify optimal postmarket surveillance strategies for medical and surgical devices. Qualitative methods were used for sampling, data collection and analysis. Stakeholders from Canada and the USA representing different roles and perspectives were first interviewed to identify examples and characteristics of different surveillance strategies. These stakeholders and others they recommended were then assembled at a 1-day nominal group meeting to discuss and prioritise the components of a postmarket device surveillance system, and research needed to achieve such a system. Consultations were held with 37 participants, and 47 participants attended the 1-day meeting. They recommended a multicomponent system including reporting by facilities, clinicians and patients, supported with some external surveillance for validation and real-time trials for high-risk devices. Many considerations were identified that constitute desirable characteristics of, and means by which to implement such a system. An overarching network was envisioned to broker linkages, establish a shared minimum dataset, and support communication and decision making. Numerous research questions were identified, which could be pursued in tandem with phased implementation of the system. These findings provide unique guidance for establishing a device safety network that is based on existing initiatives, and could be expanded and evaluated in a prospective, phased fashion as it was developed.

  14. CRISPR-Cas9 systems: versatile cancer modelling platforms and promising therapeutic strategies.

    PubMed

    Wen, Wan-Shun; Yuan, Zhi-Min; Ma, Shi-Jie; Xu, Jiang; Yuan, Dong-Tang

    2016-03-15

    The RNA-guided nuclease CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) and its variants such as nickase Cas9, dead Cas9, guide RNA scaffolds and RNA-targeting Cas9 are convenient and versatile platforms for site-specific genome editing and epigenome modulation. They are easy-to-use, simple-to-design and capable of targeting multiple loci simultaneously. Given that cancer develops from cumulative genetic and epigenetic alterations, CRISPR-Cas9 and its variants (hereafter referred to as CRISPR-Cas9 systems) hold extensive application potentials in cancer modeling and therapy. To date, they have already been applied to model oncogenic mutations in cell lines (e.g., Choi and Meyerson, Nat Commun 2014;5:3728) and in adult animals (e.g., Xue et al., Nature 2014;514:380-4), as well as to combat cancer by disabling oncogenic viruses (e.g., Hu et al., Biomed Res Int 2014;2014:612823) or by manipulating cancer genome (e.g., Liu et al., Nat Commun 2014;5:5393). Given the importance of epigenome and transcriptome in tumourigenesis, manipulation of cancer epigenome and transcriptome for cancer modeling and therapy is a promising area in the future. Whereas (epi)genetic modifications of cancer microenvironment with CRISPR-Cas9 systems for therapeutic purposes represent another promising area in cancer research. Herein, we introduce the functions and mechanisms of CRISPR-Cas9 systems in genome editing and epigenome modulation, retrospect their applications in cancer modelling and therapy, discuss limitations and possible solutions and propose future directions, in hope of providing concise and enlightening information for readers interested in this area. © 2015 UICC.

  15. Clinicians' preventive strategies for children and adolescents identified as at high risk of developing caries.

    PubMed

    Sarmadi, Roxana; Gahnberg, Lars; Gabre, Pia

    2011-05-01

    Clinicians handle diagnosis and treatment planning of caries in different ways, and the underlying factors leading to management of risk and choice of treatment strategies are poorly understood. The aim of this study was to investigate dentists' and dental hygienists' choices of preventive strategies for children and adolescents identified as at high risk of developing caries. A sample of dental records from 432 of a total of 3372 children in a Swedish county identified as at high risk of developing caries, aged 3-19 years, was randomly selected for analysis in the study. Information of importance for the therapists' choice of caries management strategies were obtained from the dental records. The results showed that therapists considered tooth brushing instruction and fluoride treatment at the clinic to be of primary importance as treatment given in 60% of the cases, respectively. Fluoride treatment at home and diet counselling were both chosen in half of the cases. Fissure sealant therapy was used in 21% of the cases, and 15% of the patients did not receive any preventive treatment at all. The results also showed that girls more often received fluoride treatment, tooth brushing instruction and oral hygiene information than boys. In the majority of the children and adolescents, several preventive measures were given. The more background factors included in the risk assessment, the more preventive measures were given. The differences between the treatments given to girls and the boys need to be further investigated. © 2010 The Authors. International Journal of Paediatric Dentistry © 2010 BSPD, IAPD and Blackwell Publishing Ltd.

  16. Workplace-based assessment: a review of user perceptions and strategies to address the identified shortcomings.

    PubMed

    Massie, Jonathan; Ali, Jason M

    2016-05-01

    Workplace based assessments (WBAs) are now commonplace in postgraduate medical training. User acceptability and engagement is essential to the success of any medical education innovation. To this end, possessing an insight into trainee and trainer perceptions towards WBAs will help identify the major problems, permitting strategies to be introduced to improve WBA implementation. A review of literature was performed to identify studies examining trainee and trainer perceptions towards WBAs. Studies were excluded if non-English or sampling a non-medical/dental population. The identified literature was synthesised for the purpose of this critical narrative review. It is clear that there is widespread negativity towards WBAs in the workplace. This has negatively impacted on the effectiveness of WBA tools as learning aids. This negativity exists in trainees but also to an extent in their trainers. Insight gained from the literature reveals three dominant problems with WBA implementation: poor understanding as to the purpose of WBAs; insufficient time available for undertaking these assessments; and inadequate training of trainers. Approaches to addressing these three problems with WBA implementation are discussed. It is likely that a variety of solutions will be required. The prevalence of negativity towards WBAs is substantial in both trainees and trainers, eroding the effectiveness of learning that is consequent upon them. The educational community must now listen to the concerns being raised by the users and consider the range of strategies being proposed to improve the experiences of trainees, and their trainers.

  17. 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.

  18. The Quality of Clinical Maternal and Neonatal Healthcare – A Strategy for Identifying ‘Routine Care Signal Functions’

    PubMed Central

    Brenner, Stephan; De Allegri, Manuela; Gabrysch, Sabine; Chinkhumba, Jobiba; Sarker, Malabika; Muula, Adamson S.

    2015-01-01

    Background A variety of clinical process indicators exists to measure the quality of care provided by maternal and neonatal health (MNH) programs. To allow comparison across MNH programs in low- and middle-income countries (LMICs), a core set of essential process indicators is needed. Although such a core set is available for emergency obstetric care (EmOC), the ‘EmOC signal functions’, a similar approach is currently missing for MNH routine care evaluation. We describe a strategy for identifying core process indicators for routine care and illustrate their usefulness in a field example. Methods We first developed an indicator selection strategy by combining epidemiological and programmatic aspects relevant to MNH in LMICs. We then identified routine care process indicators meeting our selection criteria by reviewing existing quality of care assessment protocols. We grouped these indicators into three categories based on their main function in addressing risk factors of maternal or neonatal complications. We then tested this indicator set in a study assessing MNH quality of clinical care in 33 health facilities in Malawi. Results Our strategy identified 51 routine care processes: 23 related to initial patient risk assessment, 17 to risk monitoring, 11 to risk prevention. During the clinical performance assessment a total of 82 cases were observed. Birth attendants’ adherence to clinical standards was lowest in relation to risk monitoring processes. In relation to major complications, routine care processes addressing fetal and newborn distress were performed relatively consistently, but there were major gaps in the performance of routine care processes addressing bleeding, infection, and pre-eclampsia risks. Conclusion The identified set of process indicators could identify major gaps in the quality of obstetric and neonatal care provided during the intra- and immediate postpartum period. We hope our suggested indicators for essential routine care processes

  19. Developing Mathematically Promising Students.

    ERIC Educational Resources Information Center

    Sheffield, Linda Jensen, Ed.

    This book, written on the recommendation of the Task Force on Mathematically Promising Students, investigates issues involving the development of promising mathematics students. Recommendations are made concerning topics such as the definition of promising students; the identification of such students; appropriate curriculum, instruction, and…

  20. Methodology to explore interactions between the water system and society in order to identify adaptation strategies

    NASA Astrophysics Data System (ADS)

    Offermans, A. G. E.; Haasnoot, M.

    2009-04-01

    Development of sustainable water management strategies involves analysing current and future vulnerability, identification of adaptation possibilities, effect analysis and evaluation of the strategies under different possible futures. Recent studies on water management often followed the pressure-effect chain and compared the state of social, economic and ecological functions of the water systems in one or two future situations with the current situation. The future is, however, more complex and dynamic. Water management faces major challenges to cope with future uncertainties in both the water system as well as the social system. Uncertainties in our water system relate to (changes in) drivers and pressures and their effects on the state, like the effects of climate change on discharges. Uncertainties in the social world relate to changing of perceptions, objectives and demands concerning water (management), which are often related with the aforementioned changes in the physical environment. The methodology presented here comprises the 'Perspectives method', derived from the Cultural Theory, a method on analyzing and classifying social response to social and natural states and pressures. The method will be used for scenario analysis and to identify social responses including changes in perspectives and management strategies. The scenarios and responses will be integrated within a rapid assessment tool. The purpose of the tool is to provide users with insight about the interaction of the social and physical system and to identify robust water management strategies by analysing the effectiveness under different possible futures on the physical, social and socio-economic system. This method allows for a mutual interaction between the physical and social system. We will present the theoretical background of the perspectives method as well as a historical overview of perspective changes in the Dutch Meuse area to show how social and physical systems interrelate. We

  1. A Promising Development: "Promise" Scholarships Targeting Individual Communities Reduce Barriers to College Access--and Completion

    ERIC Educational Resources Information Center

    Pierce, Dennis

    2015-01-01

    This article discusses Promise Scholarships in community colleges and sources of funding. The following community colleges and their scholarships are mentioned in this article: (1) Oregon Promise, Oregon; (2) Ventura College Promise, California; (3) Kalamazoo Promise, Michigan; (4) Pittsburgh Promise, Pennsylvania; (5) SEED Scholarship, Delaware;…

  2. 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.

  3. Stem Cell Therapy: A Promising Therapeutic Method for Intracerebral Hemorrhage.

    PubMed

    Gao, Liansheng; Xu, Weilin; Li, Tao; Chen, Jingyin; Shao, Anwen; Yan, Feng; Chen, Gao

    2018-01-01

    Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.

  4. Utility, Limitations, and Promise of Proteomics in Animal Science

    USDA-ARS?s Scientific Manuscript database

    Proteomics experiments have the ability to simultaneously identify and quantify thousands of proteins in one experiment. The use of this technology in veterinary/animal science is still in its infancy, yet it holds significant promise as a method for advancing veterinary/animal science research. E...

  5. Assessing college students' attitudes toward responsible drinking messages to identify promising binge drinking intervention strategies.

    PubMed

    Pilling, Valerie K; Brannon, Laura A

    2007-01-01

    Health communication appeals were utilized through a Web site simulation to evaluate the potential effectiveness of 3 intervention approaches to promote responsible drinking among college students. Within the Web site simulation, participants were exposed to a persuasive message designed to represent either the generalized social norms advertising approach (based on others' behavior), the personalized behavioral feedback approach (tailored to the individual's behavior), or the schema-based approach (tailored to the individual's self-schema, or personality). A control group was exposed to a message that was designed to be neutral (it was designed to discourage heavy drinking, but it did not represent any of the previously mentioned approaches). It was hypothesized that the more personalized the message was to the individual, the more favorable college students' attitudes would be toward the responsible drinking message. Participants receiving the more personalized messages did report more favorable attitudes toward the responsible drinking message.

  6. Optimal CINAHL search strategies for identifying therapy studies and review articles.

    PubMed

    Wong, Sharon S L; Wilczynski, Nancy L; Haynes, R Brian

    2006-01-01

    To design optimal search strategies for locating sound therapy studies and review articles in CiNAHL in the year 2000. An analytic survey was conducted, comparing hand searches of 75 journals with retrievals from CINAHL for 5,020 candidate search terms and 17,900 combinations for therapy and 5,977 combinations for review articles. All articles were rated with purpose and quality indicators. Candidate search strategies were used in CINAHL, and the retrievals were compared with results of the hand searches. The proposed search strategies were treated as "diagnostic tests" for sound studies and the manual review of the literature was treated as the "gold standard." Operating characteristics of the search strategies were calculated. Of the 1,383 articles about treatment, 506 (36.6%) met basic criteria for scientific merit and 127 (17.9%) of the 711 articles classified as a review met the criteria for systematic reviews. For locating sound treatment studies, a three-term strategy maximized sensitivity at 99.4% but with compromised specificity at 58.3%, and a two-term strategy maximized specificity at 98.5% but with compromised sensitivity at 52.0%. For detecting systematic reviews, a three-term strategy maximized sensitivity at 91.3% while keeping specificity high at 95.4%, and a single-term strategy maximized specificity at 99.6% but with compromised sensitivity at 42.5%. Three-term search strategies optimizing sensitivity and specificity achieved these values over 91% for detecting sound treatment studies and over 76% for detecting systematic reviews. Search strategies combining indexing terms and text words can achieve high sensitivity and specificity for retrieving sound treatment studies and review articles in CINAHL.

  7. 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.

  8. Promising Practices in Drug Treatment: Findings from Southeast Asia

    ERIC Educational Resources Information Center

    Libretto, Salvatore; Nemes, Susanna; Namur, Jenny; Garrett, Gerald; Hess, Lauren; Kaplan, Linda

    2005-01-01

    In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in three countries in Southeast Asia--Malaysia, Singapore, and Thailand--were examined to identify promising practices and to…

  9. 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.

  10. 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.

  11. Promising Practices in Drug Treatment: Findings from Latin America

    ERIC Educational Resources Information Center

    Nemes, Susanna; Libretto, Salvatore; Garrett, Gerald; Johansson, Anna Carin; Hess, Lauren

    2005-01-01

    In a study to evaluate the drug treatment and aftercare efforts sponsored by the State Department's International Narcotics and Law Enforcement Affairs Bureau, residential Therapeutic Community (TC) treatment programs in three Latin American countries--Brazil, Peru and Argentina--were examined to identify promising practices and to assess lessons…

  12. Keeping the Promise

    ERIC Educational Resources Information Center

    Whissemore, Tabitha

    2016-01-01

    Since its launch in September 2015, Heads Up America has collected information on nearly 125 promise programs across the country, many of which were instituted long before President Barack Obama announced the America's College Promise (ACP) plan in 2015. At least 27 new free community college programs have launched in states, communities, and at…

  13. Between worst and best: developing criteria to identify promising practices in health promotion and disease prevention for the Canadian Best Practices Portal.

    PubMed

    Fazal, Nadia; Jackson, Suzanne F; Wong, Katy; Yessis, Jennifer; Jetha, Nina

    2017-11-01

    In health promotion and chronic disease prevention, both best and promising practices can provide critical insights into what works for enhancing the healthrelated outcomes of individuals and communities, and how/why these practices work in different situations and contexts. The promising practices criteria were developed using the Public Health Agency of Canada's (PHAC's) existing best practices criteria as the foundation. They were modified and pilot tested (three rounds) using published interventions. Theoretical and methodological issues and challenges were resolved via consultation and in-depth discussions with a working group. The team established a set of promising practices criteria, which differentiated from the best practices criteria via six specific measures. While a number of complex challenges emerged in the development of these criteria, they were thoroughly discussed, debated and resolved. The Canadian Best Practices Portal's screening criteria allow one to screen for both best and promising practices in the fields of public health, health promotion, chronic disease prevention, and potentially beyond.

  14. The promise and pitfalls of community resilience.

    PubMed

    Uscher-Pines, Lori; Chandra, Anita; Acosta, Joie

    2013-12-01

    An important shift in terminology has occurred in emergency preparedness, and the concept of community resilience has become ubiquitous. Although enhancing community resilience is broader than preparedness, and emphasizes a distinct set of activities and participants, the terms are often used interchangeably. The implications of this shift have not been fully explored. This commentary describes the potential promise and pitfalls of the concept of community resilience and recommends strategies to overcome its limitations. We believe that resilience has the power to dramatically change this field in immense, positive ways, but some important challenges such as confusion about definitions and lack of accountability must first be overcome. (Disaster Med Public Health Preparedness. 2013;7:603-606).

  15. 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.

  16. Phage display as a promising approach for vaccine development.

    PubMed

    Aghebati-Maleki, Leili; Bakhshinejad, Babak; Baradaran, Behzad; Motallebnezhad, Morteza; Aghebati-Maleki, Ali; Nickho, Hamid; Yousefi, Mehdi; Majidi, Jafar

    2016-09-29

    Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mammalian body during a long-standing evolutionary period. The birth of phage display technology has been a turning point in the development of phage-based vaccines. Phage display vaccines are made by expressing multiple copies of an antigen on the surface of immunogenic phage particles, thereby eliciting a powerful and effective immune response. Also, the ability to produce combinatorial peptide libraries with a highly diverse pool of randomized ligands has transformed phage display into a straightforward, versatile and high throughput screening methodology for the identification of potential vaccine candidates against different diseases in particular microbial infections. These libraries can be conveniently screened through an affinity selection-based strategy called biopanning against a wide variety of targets for the selection of mimotopes with high antigenicity and immunogenicity. Also, they can be panned against the antiserum of convalescent individuals to recognize novel peptidomimetics of pathogen-related epitopes. Phage display has represented enormous promise for finding new strategies of vaccine discovery and production and current breakthroughs promise a brilliant future for the development of different phage-based vaccine platforms.

  17. Search strategies for identifying qualitative studies in CINAHL.

    PubMed

    Wilczynski, Nancy L; Marks, Susan; Haynes, R Brian

    2007-05-01

    Nurses, allied health professionals, clinicians, and researchers increasingly use online access to evidence in the course of patient care or when conducting reviews on a particular topic. Qualitative research has an important role in evidence-based health care. Online searching for qualitative studies can be difficult, however, resulting in the need to develop search filters. The objective of this study was to develop optimal search strategies to retrieve qualitative studies in CINAHL for the 2000 publishing year. The authors conducted an analytic survey comparing hand searches of journals with retrievals from CINAHL for candidate search terms and combinations. Combinations of search terms reached peak sensitivities of 98.9% and peak specificities of 99.5%. Combining search terms optimized both sensitivity and specificity at 94.2%. Empirically derived search strategies combining indexing terms and textwords can achieve high sensitivity and high specificity for retrieving qualitative studies from CINAHL.

  18. An integrative strategy to identify the entire protein coding potential of prokaryotic genomes by proteogenomics.

    PubMed

    Omasits, Ulrich; Varadarajan, Adithi R; Schmid, Michael; Goetze, Sandra; Melidis, Damianos; Bourqui, Marc; Nikolayeva, Olga; Québatte, Maxime; Patrignani, Andrea; Dehio, Christoph; Frey, Juerg E; Robinson, Mark D; Wollscheid, Bernd; Ahrens, Christian H

    2017-12-01

    Accurate annotation of all protein-coding sequences (CDSs) is an essential prerequisite to fully exploit the rapidly growing repertoire of completely sequenced prokaryotic genomes. However, large discrepancies among the number of CDSs annotated by different resources, missed functional short open reading frames (sORFs), and overprediction of spurious ORFs represent serious limitations. Our strategy toward accurate and complete genome annotation consolidates CDSs from multiple reference annotation resources, ab initio gene prediction algorithms and in silico ORFs (a modified six-frame translation considering alternative start codons) in an integrated proteogenomics database (iPtgxDB) that covers the entire protein-coding potential of a prokaryotic genome. By extending the PeptideClassifier concept of unambiguous peptides for prokaryotes, close to 95% of the identifiable peptides imply one distinct protein, largely simplifying downstream analysis. Searching a comprehensive Bartonella henselae proteomics data set against such an iPtgxDB allowed us to unambiguously identify novel ORFs uniquely predicted by each resource, including lipoproteins, differentially expressed and membrane-localized proteins, novel start sites and wrongly annotated pseudogenes. Most novelties were confirmed by targeted, parallel reaction monitoring mass spectrometry, including unique ORFs and single amino acid variations (SAAVs) identified in a re-sequenced laboratory strain that are not present in its reference genome. We demonstrate the general applicability of our strategy for genomes with varying GC content and distinct taxonomic origin. We release iPtgxDBs for B. henselae , Bradyrhizobium diazoefficiens and Escherichia coli and the software to generate both proteogenomics search databases and integrated annotation files that can be viewed in a genome browser for any prokaryote. © 2017 Omasits et al.; Published by Cold Spring Harbor Laboratory Press.

  19. Promising approaches for the treatment and prevention of viral respiratory illnesses.

    PubMed

    Papadopoulos, Nikolaos G; Megremis, Spyridon; Kitsioulis, Nikolaos A; Vangelatou, Olympia; West, Peter; Xepapadaki, Paraskevi

    2017-10-01

    Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  20. 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

  1. Service-Learning: Promise and Possibility in Post-Secondary Education

    ERIC Educational Resources Information Center

    Kalles, Susan; Ryan, Thomas G.

    2015-01-01

    Herein we identify and address promising practices, essential theories, and related cautions within service-learning. The argument that service-learning is an organized community service which is connected to curriculum in an effort to deepen learning around content was scrutinized and endorsed. We envisioned service-learning as more than a joint…

  2. Promising treatments in development for food allergies.

    PubMed

    Rancé, Fabienne

    2004-11-01

    Up to 6% of young children and 2% of adults suffer from food allergy. Among them many have IgE-mediated food allergy, a condition with potentially fatal allergic reactions. The only proven treatment is avoidance of the offending food, which can be identified using standardised allergic tests. However, several studies have addressed possible definite treatment options for food allergy. Immunotherapy, administered orally or by systemic injections, shows promising preliminary results, but these therapeutics are based on studies with insufficient scientific support, or are associated with a high risk of severe side effects. At present, no studies can support pharmacotherapy. However, promising results were recently published with anti-IgE antibodies in a human trial, and various approaches in a mouse model of food allergy (chinese herbal medicine, specific modulation of the T-cell response). Rapidly evolving findings might provide hope for a cure for food allergy in the near future.

  3. 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…

  4. Dance and Hometown Associations are Promising Strategies to Improve Physical Activity Participation Among US Nigerian Transnational Immigrants.

    PubMed

    Ibe-Lamberts, Kelechi; Tshiswaka, Daudet Ilunga; Onyenekwu, Ifeyinwa; Schwingel, Andiara; Iwelunmor, Juliet

    2018-04-01

    Lack of physical activity participation has been identified as a determinant for negative health outcomes across various ethnicities worldwide and within the USA. We investigated the perceptions of the prospects of promoting dancing within hometown associations as a form for improving physical activity participation for Nigerian Transnational Immigrants (NTIs) in the USA: a migrant cohort subset of individuals who maintain cross-border ties with their indigenous communities of origin. Using PEN-3 cultural model, we conducted semi-structured interviews with 24 transnational African migrants (11 males and 13 females) living in Chicago to explore culturally sensitive strategies to promote physical activity participation among our target population. The findings revealed positive perceptions related to dancing that might help to promote physical activity (PA) among NTI, existential or unique perceptions related to Nigerian parties that may also play a role with PA promotion, and negative perception in the form of limited discussions about PA in Nigerian hometown associations in the USA. Results from this study highlight the need for further investigation on culturally sensitive strategies to improve physical activity and participation in diverse Black immigrant populations, specifically in the form of cultural dance and activities such as parties in which this population frequently participate in. Furthermore, hometown associations may also serve as a platform for the implementation of PA programs due to its large reach to a rather covert group.

  5. Strategy for Identifying Repurposed Drugs for the Treatment of Cerebral Cavernous Malformation

    PubMed Central

    Gibson, Christopher C.; Zhu, Weiquan; Davis, Chadwick T.; Bowman-Kirigin, Jay A.; Chan, Aubrey C.; Ling, Jing; Walker, Ashley E.; Goitre, Luca; Monache, Simona Delle; Retta, Saverio Francesco; Shiu, Yan-Ting E.; Grossmann, Allie H.; Thomas, Kirk R.; Donato, Anthony J.; Lesniewski, Lisa A.; Whitehead, Kevin J.; Li, Dean Y.

    2014-01-01

    Background Cerebral cavernous malformation (CCM) is a hemorrhagic stroke disease affecting up to 0.5% of North Americans with no approved non-surgical treatment. A subset of patients have a hereditary form of the disease due primarily to loss-of-function mutations in KRIT1, CCM2, or PDCD10. We sought to identify known drugs that could be repurposed to treat CCM. Methods and Results We developed an unbiased screening platform based on both cellular and animal models of loss-of-function of CCM2. Our discovery strategy consisted of four steps: an automated immunofluorescence and machine-learning-based primary screen of structural phenotypes in human endothelial cells deficient in CCM2; a secondary screen of functional changes in endothelial stability in these same cells; a rapid in vivo tertiary screen of dermal microvascular leak in mice lacking endothelial Ccm2; and finally a quaternary screen of CCM lesion burden in these same mice. We screened 2,100 known drugs and bioactive compounds, and identified two candidates for further study, cholecalciferol (Vitamin D3) and tempol (a scavenger of superoxide). Each drug decreased lesion burden in a mouse model of CCM vascular disease by approximately 50%. Conclusions By identifying known drugs as potential therapeutics for CCM, we have decreased the time, cost, and risk of bringing treatments to patients. Each drug also prompts additional exploration of biomarkers of CCM disease. We further suggest that the structure-function screening platform presented here may be adapted and scaled to facilitate drug discovery for diverse loss-of-function genetic vascular disease. PMID:25486933

  6. Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

    PubMed

    Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

    2015-01-01

    Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

  7. The Utility, Limitations, and Promise of Proteomics in Animal Science

    USDA-ARS?s Scientific Manuscript database

    Proteomics experiments have the ability to simultaneously identify and quantify potentially thousands of proteins in one experiment. The use of this technology in animal science is still in its infancy, yet it holds significant promise as a method for advancing animal science research. Examples of...

  8. Improving High School Success: Searching for Evidence of Promise

    ERIC Educational Resources Information Center

    Mazzeo, Christopher; Fleischman, Steve; Heppen, Jessica; Jahangir, Theresa

    2016-01-01

    Improving the nation's high schools--particularly those that are low-performing--involves challenges that are far easier to catalog than to surmount. In this chapter, the authors identify a handful of promising approaches that can help to achieve the goal that all students will graduate from high school well-prepared for further learning,…

  9. Predictive Validity of an Empirical Approach for Selecting Promising Message Topics: A Randomized-Controlled Study

    PubMed Central

    Lee, Stella Juhyun; Brennan, Emily; Gibson, Laura Anne; Tan, Andy S. L.; Kybert-Momjian, Ani; Liu, Jiaying; Hornik, Robert

    2016-01-01

    Several message topic selection approaches propose that messages based on beliefs pretested and found to be more strongly associated with intentions will be more effective in changing population intentions and behaviors when used in a campaign. This study aimed to validate the underlying causal assumption of these approaches which rely on cross-sectional belief–intention associations. We experimentally tested whether messages addressing promising themes as identified by the above criterion were more persuasive than messages addressing less promising themes. Contrary to expectations, all messages increased intentions. Interestingly, mediation analyses showed that while messages deemed promising affected intentions through changes in targeted promising beliefs, messages deemed less promising also achieved persuasion by influencing nontargeted promising beliefs. Implications for message topic selection are discussed. PMID:27867218

  10. 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.

  11. The social process of escalation: a promising focus for crisis management research

    PubMed Central

    2012-01-01

    Background This study identifies a promising, new focus for the crisis management research in the health care domain. After reviewing the literature on health care crisis management, there seems to be a knowledge-gap regarding organisational change and adaption, especially when health care situations goes from normal, to non-normal, to pathological and further into a state of emergency or crisis. Discussion Based on studies of escalating situations in obstetric care it is suggested that two theoretical perspectives (contingency theory and the idea of failure as a result of incomplete interaction) tend to simplify the issue of escalation rather than attend to its complexities (including the various power relations among the stakeholders involved). However studying the process of escalation as inherently complex and social allows us to see the definition of a situation as normal or non-normal as an exercise of power in itself, rather than representing a putatively correct response to a particular emergency. Implications The concept of escalation, when treated this way, can help us further the analysis of clinical and institutional acts and competence. It can also turn our attention to some important elements in a class of social phenomenon, crises and emergencies, that so far have not received the attention they deserve. Focusing on organisational choreography, that interplay of potential factors such as power, professional identity, organisational accountability, and experience, is not only a promising focus for future naturalistic research but also for developing more pragmatic strategies that can enhance organisational coordination and response in complex events. PMID:22704075

  12. Identifying optimal agricultural countermeasure strategies for a hypothetical contamination scenario using the strategy model.

    PubMed

    Cox, G; Beresford, N A; Alvarez-Farizo, B; Oughton, D; Kis, Z; Eged, K; Thørring, H; Hunt, J; Wright, S; Barnett, C L; Gil, J M; Howard, B J; Crout, N M J

    2005-01-01

    A spatially implemented model designed to assist the identification of optimal countermeasure strategies for radioactively contaminated regions is described. Collective and individual ingestion doses for people within the affected area are estimated together with collective exported ingestion dose. A range of countermeasures are incorporated within the model, and environmental restrictions have been included as appropriate. The model evaluates the effectiveness of a given combination of countermeasures through a cost function which balances the benefit obtained through the reduction in dose with the cost of implementation. The optimal countermeasure strategy is the combination of individual countermeasures (and when and where they are implemented) which gives the lowest value of the cost function. The model outputs should not be considered as definitive solutions, rather as interactive inputs to the decision making process. As a demonstration the model has been applied to a hypothetical scenario in Cumbria (UK). This scenario considered a published nuclear power plant accident scenario with a total deposition of 1.7x10(14), 1.2x10(13), 2.8x10(10) and 5.3x10(9)Bq for Cs-137, Sr-90, Pu-239/240 and Am-241, respectively. The model predicts that if no remediation measures were implemented the resulting collective dose would be approximately 36 000 person-Sv (predominantly from 137Cs) over a 10-year period post-deposition. The optimal countermeasure strategy is predicted to avert approximately 33 000 person-Sv at a cost of approximately 160 million pounds. The optimal strategy comprises a mixture of ploughing, AFCF (ammonium-ferric hexacyano-ferrate) administration, potassium fertiliser application, clean feeding of livestock and food restrictions. The model recommends specific areas within the contaminated area and time periods where these measures should be implemented.

  13. The Promise of Virtual Teams: Identifying Key Factors in Effectiveness and Failure

    ERIC Educational Resources Information Center

    Horwitz, Frank M.; Bravington, Desmond; Silvis, Ulrik

    2006-01-01

    Purpose: The aim of the investigation is to identify enabling and disenabling factors in the development and operation of virtual teams; to evaluate the importance of factors such as team development, cross-cultural variables, leadership, communication and social cohesion as contributors to virtual team effectiveness. Design/methodology/approach:…

  14. 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

  15. 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

  16. Promising More Information

    NASA Technical Reports Server (NTRS)

    2003-01-01

    When NASA needed a real-time, online database system capable of tracking documentation changes in its propulsion test facilities, engineers at Stennis Space Center joined with ECT International, of Brookfield, Wisconsin, to create a solution. Through NASA's Dual-Use Program, ECT developed Exdata, a software program that works within the company's existing Promise software. Exdata not only satisfied NASA s requirements, but also expanded ECT s commercial product line. Promise, ECT s primary product, is an intelligent software program with specialized functions for designing and documenting electrical control systems. An addon to AutoCAD software, Promis e generates control system schematics, panel layouts, bills of material, wire lists, and terminal plans. The drawing functions include symbol libraries, macros, and automatic line breaking. Primary Promise customers include manufacturing companies, utilities, and other organizations with complex processes to control.

  17. 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.

  18. 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

  19. 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…

  20. Promising SINEs for embargoing nuclear-cytoplasmic export as an anticancer strategy.

    PubMed

    Tan, David S P; Bedard, Philippe L; Kuruvilla, John; Siu, Lillian L; Razak, Albiruni R Abdul

    2014-05-01

    In cancer cells, the nuclear-cytoplasmic transport machinery is frequently disrupted, resulting in mislocalization and loss of function for many key regulatory proteins. In this review, the mechanisms by which tumor cells co-opt the nuclear transport machinery to facilitate carcinogenesis, cell survival, drug resistance, and tumor progression will be elucidated, with a particular focus on the role of the nuclear-cytoplasmic export protein. The recent development of a new generation of selective inhibitors of nuclear export (XPO1 antagonists) and how these novel anticancer drugs may bring us closer to the implementation of this therapeutic strategy in the clinic will be discussed.

  1. The accuracy and cost-effectiveness of strategies used to identify peripheral artery disease among patients with diabetic foot ulcers.

    PubMed

    Barshes, Neal R; Flores, Everardo; Belkin, Michael; Kougias, Panos; Armstrong, David G; Mills, Joseph L

    2016-12-01

    Patients with diabetic foot ulcers (DFUs) should be evaluated for peripheral artery disease (PAD). We sought to estimate the overall diagnostic accuracy for various strategies that are used to identify PAD in this population. A Markov model with probabilistic and deterministic sensitivity analyses was used to simulate the clinical events in a population of 10,000 patients with diabetes. One of 14 different diagnostic strategies was applied to those who developed DFUs. Baseline data on diagnostic accuracy of individual noninvasive tests were based on a meta-analysis of previously reported studies. The overall sensitivity and cost-effectiveness of the 14 strategies were then compared. The overall sensitivity of various combinations of diagnostic testing strategies ranged from 32.6% to 92.6%. Cost-effective strategies included ankle-brachial indices for all patients; skin perfusion pressures (SPPs) or toe-brachial indices (TBIs) for all patients; and SPPs or TBIs to corroborate normal pulse examination findings, a strategy that lowered leg amputation rates by 36%. Strategies that used noninvasive vascular testing to investigate only abnormal pulse examination results had low overall diagnostic sensitivity and were weakly dominated in cost-effectiveness evaluations. Population prevalence of PAD did not alter strategy ordering by diagnostic accuracy or cost-effectiveness. TBIs or SPPs used uniformly or to corroborate a normal pulse examination finding are among the most sensitive and cost-effective strategies to improve the identification of PAD among patients presenting with DFUs. These strategies may significantly reduce leg amputation rates with only modest increases in cost. Published by Elsevier Inc.

  2. 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

  3. The Syrian hamster embryo cells transformation assay identifies efficiently nongenotoxic carcinogens, and can contribute to alternative, integrated testing strategies.

    PubMed

    Benigni, Romualdo; Bossa, Cecilia; Tcheremenskaia, Olga; Battistelli, Chiara Laura; Giuliani, Alessandro

    2015-02-01

    The long-term carcinogenesis bioassays have played a central role in protecting human health, but for ethical and practical reasons their use is dramatically diminishing and the genotoxicity short-term tests have taken the pivotal role in the pre-screening of chemical carcinogenicity. However, this strategy cannot detect nongenotoxic carcinogens. Since up to 25% of IARC human carcinogens are recognized to have nongenotoxic mechanisms of action, the risk they pose to human health cannot be disregarded, and it is urgent to fill the gap in the tools for alternative testing. In this paper, we analyze from different perspectives the ability of Cell Transformation Assays to identify nongenotoxic carcinogens, and we conclude that the Syrian hamster embryo cells test is able to identify nongenotoxic carcinogens with 80-90% efficiency, and thus, can play an important role in integrated, alternative testing strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. 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

  5. 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.

  6. Costs, equity, efficiency and feasibility of identifying the poor in Ghana's National Health Insurance Scheme: empirical analysis of various strategies.

    PubMed

    Aryeetey, Genevieve Cecilia; Jehu-Appiah, Caroline; Spaan, Ernst; Agyepong, Irene; Baltussen, Rob

    2012-01-01

    To analyse the costs and evaluate the equity, efficiency and feasibility of four strategies to identify poor households for premium exemptions in Ghana's National Health Insurance Scheme (NHIS): means testing (MT), proxy means testing (PMT), participatory wealth ranking (PWR) and geographic targeting (GT) in urban, rural and semi-urban settings in Ghana. We conducted the study in 145-147 households per setting with MT as our gold standard strategy. We estimated total costs that included costs of household surveys and cost of premiums paid to the poor, efficiency (cost per poor person identified), equity (number of true poor excluded) and the administrative feasibility of implementation. The cost of exempting one poor individual ranged from US$15.87 to US$95.44; exclusion of the poor ranged between 0% and 73%. MT was most efficient and equitable in rural and urban settings with low-poverty incidence; GT was efficient and equitable in the semi-urban setting with high-poverty incidence. PMT and PWR were less equitable and inefficient although feasible in some settings. We recommend MT as optimal strategy in low-poverty urban and rural settings and GT as optimal strategy in high-poverty semi-urban setting. The study is relevant to other social and developmental programmes that require identification and exemptions of the poor in low-income countries. © 2011 Blackwell Publishing Ltd.

  7. 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.

  8. A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus.

    PubMed

    Cheng, Han; Koning, Katie; O'Hearn, Aileen; Wang, Minxiu; Rumschlag-Booms, Emily; Varhegyi, Elizabeth; Rong, Lijun

    2015-11-24

    Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.

  9. Nanoparticles for the delivery of therapeutic antibodies: Dogma or promising strategy?

    PubMed

    Sousa, Flávia; Castro, Pedro; Fonte, Pedro; Kennedy, Patrick J; Neves-Petersen, Maria Teresa; Sarmento, Bruno

    2017-10-01

    Over the past two decades, therapeutic antibodies have demonstrated promising results in the treatment of a wide array of diseases. However, the application of antibody-based therapy implies multiple administrations and a high cost of antibody production, resulting in costly therapy. Another disadvantage inherent to antibody-based therapy is the limited stability of antibodies and the low level of tissue penetration. The use of nanoparticles as delivery systems for antibodies allows for a reduction in antibody dosing and may represent a suitable alternative to increase antibody stability Areas covered: We discuss different nanocarriers intended for the delivery of antibodies as well as the corresponding encapsulation methods. Recent developments in antibody nanoencapsulation, particularly the possible toxicity issues that may arise from entrapment of antibodies into nanocarriers, are also assessed. In addition, this review will discuss the alterations in antibody structure and bioactivity that occur with nanoencapsulation. Expert opinion: Nanocarriers can protect antibodies from degradation, ensuring superior bioavailability. Encapsulation of therapeutic antibodies may offer some advantages, including potential targeting, reduced immunogenicity and controlled release. Furthermore, antibody nanoencapsulation may aid in the incorporation of the antibodies into the cells, if intracellular components (e.g. intracellular enzymes, oncogenic proteins, transcription factors) are to be targeted.

  10. Porous liquids: A promising class of media for gas separation

    DOE PAGES

    Zhang, Jinshui; Chai, Song -Hai; Qiao, Zhen -An; ...

    2014-11-17

    In porous liquids with empty cavities we successfully has been successfully fabricated by surface engineering of hollow structures with suitable corona and canopy species. By taking advantage of the liquid-like polymeric matrices as a separation medium and the empty cavities as gas transport pathway, this unique porous liquid can function as a promising candidate for gas separation. A facile synthetic strategy can be further extended to other types of nanostructure-based porous liquid fabrication, opening up new opportunities for preparation of porous liquids with attractive properties for specific tasks.

  11. How to reduce sitting time? A review of behaviour change strategies used in sedentary behaviour reduction interventions among adults.

    PubMed

    Gardner, Benjamin; Smith, Lee; Lorencatto, Fabiana; Hamer, Mark; Biddle, Stuart J H

    2016-01-01

    Sedentary behaviour - i.e., low energy-expending waking behaviour while seated or lying down - is a health risk factor, even when controlling for physical activity. This review sought to describe the behaviour change strategies used within interventions that have sought to reduce sedentary behaviour in adults. Studies were identified through existing literature reviews, a systematic database search, and hand-searches of eligible papers. Interventions were categorised as 'very promising', 'quite promising', or 'non-promising' according to observed behaviour changes. Intervention functions and behaviour change techniques were compared across promising and non-promising interventions. Twenty-six eligible studies reported thirty-eight interventions, of which twenty (53%) were worksite-based. Fifteen interventions (39%) were very promising, eight quite promising (21%), and fifteen non-promising (39%). Very or quite promising interventions tended to have targeted sedentary behaviour instead of physical activity. Interventions based on environmental restructuring, persuasion, or education were most promising. Self-monitoring, problem solving, and restructuring the social or physical environment were particularly promising behaviour change techniques. Future sedentary reduction interventions might most fruitfully incorporate environmental modification and self-regulatory skills training. The evidence base is, however, weakened by low-quality evaluation methods; more RCTs, employing no-treatment control groups, and collecting objective data are needed.

  12. A Strategy for Identifying Quantitative Trait Genes Using Gene Expression Analysis and Causal Analysis.

    PubMed

    Ishikawa, Akira

    2017-11-27

    Large numbers of quantitative trait loci (QTL) affecting complex diseases and other quantitative traits have been reported in humans and model animals. However, the genetic architecture of these traits remains elusive due to the difficulty in identifying causal quantitative trait genes (QTGs) for common QTL with relatively small phenotypic effects. A traditional strategy based on techniques such as positional cloning does not always enable identification of a single candidate gene for a QTL of interest because it is difficult to narrow down a target genomic interval of the QTL to a very small interval harboring only one gene. A combination of gene expression analysis and statistical causal analysis can greatly reduce the number of candidate genes. This integrated approach provides causal evidence that one of the candidate genes is a putative QTG for the QTL. Using this approach, I have recently succeeded in identifying a single putative QTG for resistance to obesity in mice. Here, I outline the integration approach and discuss its usefulness using my studies as an example.

  13. 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

  14. The Kalamazoo Promise Scholarship

    ERIC Educational Resources Information Center

    Bartik, Timothy J.; Lachowska, Marta

    2014-01-01

    This study takes advantage of the unexpected announcement of the Kalamazoo Promise to study its effects on student achievement and behavior in high school. The Kalamazoo Promise provides college scholarships to graduates of Kalamazoo Public Schools (KPS), a midsized urban school district in Michigan that is racially and economically diverse.…

  15. Identifying health facilities outside the enterprise: challenges and strategies for supporting health reform and meaningful use.

    PubMed

    Dixon, Brian E; Colvard, Cyril; Tierney, William M

    2014-06-24

    Objective: To support collation of data for disability determination, we sought to accurately identify facilities where care was delivered across multiple, independent hospitals and clinics. Methods: Data from various institutions' electronic health records were merged and delivered as continuity of care documents to the United States Social Security Administration (SSA). Results: Electronic records for nearly 8000 disability claimants were exchanged with SSA. Due to the lack of standard nomenclature for identifying the facilities in which patients received the care documented in the electronic records, SSA could not match the information received with information provided by disability claimants. Facility identifiers were generated arbitrarily by health care systems and therefore could not be mapped to the existing international standards. Discussion: We propose strategies for improving facility identification in electronic health records to support improved tracking of a patient's care between providers to better serve clinical care delivery, disability determination, health reform and meaningful use. Conclusion: Accurately identifying the facilities where health care is delivered to patients is important to a number of major health reform and improvement efforts underway in many nations. A standardized nomenclature for identifying health care facilities is needed to improve tracking of care and linking of electronic health records.

  16. Comparing spatially explicit ecological and social values for natural areas to identify effective conservation strategies.

    PubMed

    Bryan, Brett Anthony; Raymond, Christopher Mark; Crossman, Neville David; King, Darran

    2011-02-01

    Consideration of the social values people assign to relatively undisturbed native ecosystems is critical for the success of science-based conservation plans. We used an interview process to identify and map social values assigned to 31 ecosystem services provided by natural areas in an agricultural landscape in southern Australia. We then modeled the spatial distribution of 12 components of ecological value commonly used in setting spatial conservation priorities. We used the analytical hierarchy process to weight these components and used multiattribute utility theory to combine them into a single spatial layer of ecological value. Social values assigned to natural areas were negatively correlated with ecological values overall, but were positively correlated with some components of ecological value. In terms of the spatial distribution of values, people valued protected areas, whereas those natural areas underrepresented in the reserve system were of higher ecological value. The habitats of threatened animal species were assigned both high ecological value and high social value. Only small areas were assigned both high ecological value and high social value in the study area, whereas large areas of high ecological value were of low social value, and vice versa. We used the assigned ecological and social values to identify different conservation strategies (e.g., information sharing, community engagement, incentive payments) that may be effective for specific areas. We suggest that consideration of both ecological and social values in selection of conservation strategies can enhance the success of science-based conservation planning. ©2010 Society for Conservation Biology.

  17. Gender Equity Expert Panel: Exemplary & Promising Gender Equity Programs, 2000.

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC.

    The U.S. Department of Education developed the Gender Equity Expert Panel to identify promising and exemplary programs that promote gender equity in and through education. This panel of experts reviewed self-nominated programs to determine whether they met four criteria: evidence of success/effectiveness in promoting gender equity; quality of the…

  18. Promising Directions for Research Regarding Adult Education in Latin America.

    ERIC Educational Resources Information Center

    Knox, Alan B.

    Documents about adult education in Latin America at the Survey and Analysis Center of the Adult Education Association of the U.S.A. were reviewed to identify promising research directions. A theoretical framework for research should be developed and should include definitions of concepts and variables in different settings and identification of…

  19. 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.

  20. 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…

  1. Multiple strategies of oxygen supply in Drosophila malignancies identify tracheogenesis as a novel cancer hallmark.

    PubMed

    Grifoni, Daniela; Sollazzo, Manuela; Fontana, Elisabetta; Froldi, Francesca; Pession, Annalisa

    2015-03-12

    Angiogenesis is the term used to describe all the alterations in blood vessel growth induced by a tumour mass following hypoxic stress. The occurrence of multiple strategies of vessel recruitment favours drug resistance, greatly complicating the treatment of certain tumours. In Drosophila, oxygen is conveyed to the internal organs by the tracheal system, a closed tubular network whose role in cancer growth is so far unexplored. We found that, as observed in human cancers, Drosophila malignant cells suffer from oxygen shortage, release pro-tracheogenic factors, co-opt nearby vessels and get incorporated into the tracheal walls. We also found that the parallelisms observed in cellular behaviours are supported by genetic and molecular conservation. Finally, we identified a molecular circuitry associated with the differentiation of cancer cells into tracheal cells. In summary, our findings identify tracheogenesis as a novel cancer hallmark in Drosophila, further expanding the power of the fly model in cancer research.

  2. 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…

  3. Generating demand for pharmacist-provided medication therapy management: identifying patient-preferred marketing strategies.

    PubMed

    Garcia, Gladys M; Snyder, Margie E; McGrath, Stephanie Harriman; Smith, Randall B; McGivney, Melissa Somma

    2009-01-01

    To identify effective strategies for marketing pharmacist-provided medication therapy management (MTM) services to patients in a self-insured employer setting. Qualitative study. University of Pittsburgh during March through May 2008. 26 university employees taking at least one chronic medication. Three focus group sessions were conducted using a semistructured topic guide to facilitate the discussion. Employees' perceived medication-related needs, perceived benefits of pharmacist-provided MTM, potential barriers for employee participation in MTM, and effective strategies for marketing MTM. Participants reported concerns with timing of doses, medication costs, access, and ensuring adherence. Participants generally felt positively toward pharmacists; however, the level of reported patient contact with pharmacists varied among participants. Some participants questioned pharmacists' education and qualifications for this enhanced role in patient care. Perceived benefits of MTM noted by participants included the opportunity to obtain personalized information about their medications and the potential for improved communication among their health providers. Barriers to patient participation were out-of-pocket costs and lack of time for MTM visits. Participants suggested use of alternative words to describe MTM and marketing approaches that involve personal contact. Pharmacists should emphasize parts of MTM that patients feel are most beneficial (i.e., provision of a personal medication record) and use patient-friendly language to describe MTM when marketing their practice. Patients will need greater exposure to the concept of MTM and the pharmacists' role in order to correctly describe and assign value to this type of pharmacist patient care practice.

  4. The promise of molecular epidemiology in defining the association between radiation and cancer

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

    Neta, R.

    2000-07-01

    Molecular epidemiology involves the inclusion in epidemiologic studies of biologic measurements made at a genetic and molecular level and aims to improve the current knowledge of disease etiology and risk. One of the goals of molecular epidemiology studies of cancer is to determine the role of environmental and genetic factors in initiation and progression of malignancies and to use this knowledge to develop preventive strategies. This approach promises extraordinary opportunities for revolutionizing the practice of medicine and reducing risk. However, this will be accompanied by the need to address and resolve many challenges, such as ensuring the appropriate interpretation ofmore » molecular testing and resolving associated ethical, legal, and social issues. Traditional epidemiologic approaches determined that exposure to ionizing radiation poses significantly increased risk of leukemia and several other types of cancer. Such studies provided the basis for setting exposure standards to protect the public and the workforce from potentially adverse effects of ionizing radiation. These standards were set by using modeling approaches to extrapolate from the biological effects observed in high-dose radiation studies to predicted, but mostly immeasurable, effects at low radiation doses. It is anticipated that the addition of the molecular parameters to the population-based studies will help identify the genes and pathways characteristic of cancers due to radiation exposure of individuals, as well as identify susceptible or resistant subpopulations. In turn, the information about the molecular mechanisms should aid to improve risk assessment. While studies on radiogenic concerns are currently limited to only a few candidate genes, the exponential growth of scientific knowledge and technology promises expansion of knowledge about identity of participating genes and pathways in the future. This article is meant to provide an introductory overview of recent advances in

  5. 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.

  6. 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.

  7. Application of microorganisms in concrete: a promising sustainable strategy to improve concrete durability.

    PubMed

    Wang, Jianyun; Ersan, Yusuf Cagatay; Boon, Nico; De Belie, Nele

    2016-04-01

    The beneficial effect of microbially induced carbonate precipitation on building materials has been gradually disclosed in the last decade. After the first applications of on historical stones, promising results were obtained with the respect of improved durability. An extensive study then followed on the application of this environmentally friendly and compatible material on a currently widely used construction material, concrete. This review is focused on the discussion of the impact of the two main applications, bacterial surface treatment and bacteria based crack repair, on concrete durability. Special attention was paid to the choice of suitable bacteria and the metabolic pathway aiming at their functionality in concrete environment. Interactions between bacterial cells and cementitious matrix were also elaborated. Furthermore, recommendations to improve the effectiveness of bacterial treatment are provided. Limitations of current studies, updated applications and future application perspectives are shortly outlined.

  8. CD22: A Promising Target for Acute Lymphoblastic Leukemia Treatment | Center for Cancer Research

    Cancer.gov

    There are about 4,000 new cases of acute lymphoblastic leukemia (ALL) in the United States each year. Great improvements have been made in the treatment of ALL, but many patients suffer from side effects of standard therapy and continue to die of this disease. One of the most promising therapeutic strategies includes engineering T cells with a chimeric antigen receptor (CAR)

  9. Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies

    PubMed Central

    Doctor, Allan; Zimmerman, Jerry; Agus, Michael; Rajasekaran, Surender; Wardenburg, Juliane Bubeck; Fortenberry, James; Zajicek, Anne; Typpo, Katri

    2016-01-01

    Objective To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome (MODS) presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015). Data Sources Literature review, research data, and expert opinion. Study Selection Not applicable. Data Extraction Moderated by an expert from the field, issues relevant to the association of MODS with a variety of conditions were presented, discussed and debated with a focus on identifying knowledge gaps and research priorities. Data Synthesis Summary of presentations and discussion supported and supplemented by relevant literature. Conclusions Among critically ill children, MODS is relatively common and associated with significant morbidity and mortality. For outcomes to improve, effective therapies aimed at preventing and treating this condition must be discovered and rigorously evaluated. In this manuscript, a number of potential opportunities to enhance current care are highlighted including the need for a better understanding of the pharmacokinetics and pharmacodynamics of medications, the effect of early and optimized nutrition, and the impact of effective glucose control in the setting of MODS. Additionally, a handful of the promising therapies either currently being implemented or developed are described. These include extracorporeal therapies, anti-cytokine therapies, anti-toxin treatments, anti-oxidant approaches and multiple forms of exogenous steroids. For the field to advance, these and other therapies must be assessed in rigorous manner and implemented accordingly. PMID:28248836

  10. 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.

  11. 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.

  12. Promising Fuel Cycle Options for R&D – Results, Insights, and Future Directions

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

    Wigeland, Roald Arnold

    2015-05-01

    The Fuel Cycle Options (FCO) campaign in the U.S. DOE Fuel Cycle Research & Development Program conducted a detailed evaluation and screening of nuclear fuel cycles. The process for this study was described at the 2014 ICAPP meeting. This paper reports on detailed insights and questions from the results of the study. The comprehensive study identified continuous recycle in fast reactors as the most promising option, using either U/Pu or U/TRU recycle, and potentially in combination with thermal reactors, as reported at the ICAPP 2014 meeting. This paper describes the examination of the results in detail that indicated that theremore » was essentially no difference in benefit between U/Pu and U/TRU recycle, prompting questions about the desirability of pursuing the more complex U/TRU approach given that the estimated greater challenges for development and deployment. The results will be reported from the current effort that further explores what, if any, benefits of TRU recycle (minor actinides in addition to plutonium recycle) may be in order to inform decisions on future R&D directions. The study also identified continuous recycle using thorium-based fuel cycles as potentially promising, in either fast or thermal systems, but with lesser benefit. Detailed examination of these results indicated that the lesser benefit was confined to only a few of the evaluation metrics, identifying the conditions under which thorium-based fuel cycles would be promising to pursue. For the most promising fuel cycles, the FCO is also conducting analyses on the potential transition to such fuel cycles to identify the issues, challenges, and the timing for critical decisions that would need to be made to avoid unnecessary delay in deployment, including investigation of issues such as the effects of a temporary lack of plutonium fuel resources or supporting infrastructure. These studies are placed in the context of an overall analysis approach designed to provide comprehensive

  13. 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.

  14. Identifying Strategies to Decrease Overtime, Absenteeism and Agency Use: Insights from Healthcare Leaders.

    PubMed

    Jeffs, Lianne; Grinspun, Doris; Closson, Tom; Mainville, Marie-Claude

    2015-09-01

    Working overtime, absenteeism and agency use can negatively impact working environments, the health of staff and patient outcomes, and increase healthcare costs. The purpose of this study was to explore how healthcare leaders in Ontario hospitals implement and sustain best practices that advance workforce stability within their organization. Qualitative study design using semi-structured interviews and thematic analysis. Participants included 23 healthcare leaders from 16 hospital sites. Two main themes emerged: (1) enacting proactive human resource practices and (2) having strong, caring and strategic leaders that create learning and supportive work environments. A number of sub-themes identified were reported through narratives stratified according to size (small/large) and performance (low/high) of each site. Insights gained from this study may offer healthcare leaders strategies to maximize the nursing workforce and minimize overtime, absenteeism and agency use to ensure safe, efficient and quality healthcare. Copyright © 2015 Longwoods Publishing.

  15. 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.

  16. A gene-trap strategy identifies quiescence-induced genes in synchronized myoblasts.

    PubMed

    Sambasivan, Ramkumar; Pavlath, Grace K; Dhawan, Jyotsna

    2008-03-01

    Cellular quiescence is characterized not only by reduced mitotic and metabolic activity but also by altered gene expression. Growing evidence suggests that quiescence is not merely a basal state but is regulated by active mechanisms. To understand the molecular programme that governs reversible cell cycle exit, we focused on quiescence-related gene expression in a culture model of myogenic cell arrest and activation. Here we report the identification of quiescence-induced genes using a gene-trap strategy. Using a retroviral vector, we generated a library of gene traps in C2C12 myoblasts that were screened for arrest-induced insertions by live cell sorting (FACS-gal). Several independent gene- trap lines revealed arrest-dependent induction of betagal activity, confirming the efficacy of the FACS screen. The locus of integration was identified in 15 lines. In three lines,insertion occurred in genes previously implicated in the control of quiescence, i.e. EMSY - a BRCA2--interacting protein, p8/com1 - a p300HAT -- binding protein and MLL5 - a SET domain protein. Our results demonstrate that expression of chromatin modulatory genes is induced in G0, providing support to the notion that this reversibly arrested state is actively regulated.

  17. 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

  18. 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.

  19. Promising Practices in Citywide Afterschool Initiatives. CityWorks: Focus on Infrastructure.

    ERIC Educational Resources Information Center

    Hall, Georgia

    This brief is the first in a series featuring promising practices in city-wide after-school initiatives, with a focus at the infrastructure level, focusing on the infrastructure representing the underlying elements or framework that hold a system or initiative together. The brief identifies practices to support the public relations function and…

  20. How to reduce sitting time? A review of behaviour change strategies used in sedentary behaviour reduction interventions among adults

    PubMed Central

    Gardner, Benjamin; Smith, Lee; Lorencatto, Fabiana; Hamer, Mark; Biddle, Stuart JH

    2016-01-01

    Sedentary behaviour – i.e., low energy-expending waking behaviour while seated or lying down – is a health risk factor, even when controlling for physical activity. This review sought to describe the behaviour change strategies used within interventions that have sought to reduce sedentary behaviour in adults. Studies were identified through existing literature reviews, a systematic database search, and hand-searches of eligible papers. Interventions were categorised as ‘very promising’, ‘quite promising’, or ‘non-promising’ according to observed behaviour changes. Intervention functions and behaviour change techniques were compared across promising and non-promising interventions. Twenty-six eligible studies reported thirty-eight interventions, of which twenty (53%) were worksite-based. Fifteen interventions (39%) were very promising, eight quite promising (21%), and fifteen non-promising (39%). Very or quite promising interventions tended to have targeted sedentary behaviour instead of physical activity. Interventions based on environmental restructuring, persuasion, or education were most promising. Self-monitoring, problem solving, and restructuring the social or physical environment were particularly promising behaviour change techniques. Future sedentary reduction interventions might most fruitfully incorporate environmental modification and self-regulatory skills training. The evidence base is, however, weakened by low-quality evaluation methods; more RCTs, employing no-treatment control groups, and collecting objective data are needed. PMID:26315814

  1. Chalcone Derivatives: Promising Starting Points for Drug Design.

    PubMed

    Gomes, Marcelo N; Muratov, Eugene N; Pereira, Maristela; Peixoto, Josana C; Rosseto, Lucimar P; Cravo, Pedro V L; Andrade, Carolina H; Neves, Bruno J

    2017-07-25

    Medicinal chemists continue to be fascinated by chalcone derivatives because of their simple chemistry, ease of hydrogen atom manipulation, straightforward synthesis, and a variety of promising biological activities. However, chalcones have still not garnered deserved attention, especially considering their high potential as chemical sources for designing and developing new effective drugs. In this review, we summarize current methodological developments towards the design and synthesis of new chalcone derivatives and state-of-the-art medicinal chemistry strategies (bioisosterism, molecular hybridization, and pro-drug design). We also highlight the applicability of computer-assisted drug design approaches to chalcones and address how this may contribute to optimizing research outputs and lead to more successful and cost-effective drug discovery endeavors. Lastly, we present successful examples of the use of chalcones and suggest possible solutions to existing limitations.

  2. 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

  3. Promising systemic immunotherapies in head and neck squamous cell carcinoma

    PubMed Central

    Gildener-Leapman, Neil; Ferris, Robert L.; Bauman, Julie E.

    2016-01-01

    SUMMARY Patients with head and neck squamous cell carcinoma (HNSCC) demonstrate poor survival and significant treatment morbidity with standard therapy. The immune profile in HNSCC, whether caused by carcinogen exposure or human papillomavirus (HPV), is notably immunosuppressive. Early clinical trials of immunotherapy in HNSCC were troubled by systemic toxicity or difficulties in local administration. Now, interest in immunotherapy has been revitalized by mechanistic insights into immune evasion by HNSCC, coupled to ongoing development of novel immunotherapies. This review will summarize immune escape mechanisms in HNSCC, namely downregulation of tumor antigen (TA) presentation, aberrant regulation of the signal transducer and activator of transcription (STAT) family, the immunosuppressive cytokine milieu, and dysregulation of immune effector cells. Therapeutic strategies hypothesized to specifically counter HNSCC immunosuppression will then be discussed. We will survey TA-targeted monoclonal antibodies (mAb), including the prototype cetuximab, as well as adjunctive strategies to enhance antibody-dependent cell-mediated cytotoxicity. We will review immunomodulation to restore STAT1/STAT3 activation balance. Examples of mAb therapy to block immunosuppressive cytokines, such as interleukin-6 or VEGF, will be provided. mAbs which release co-inhibitory T cell receptors such as CTLA-4 and PD-1, overexpressed in HNSCC, also hold therapeutic promise. Finally, we will describe principles for therapeutic vaccination in HPV-associated HNSCC, where non-host TAs such as viral oncoproteins represent ideal targets, and HPV-negative HNSCC, where p53 is a promising target. Insights into immunosuppression in HNSCC have elucidated mechanistic targets for immunotherapy. Rational clinical investigation may lead to effective stand alone or combinatorial treatment approaches. PMID:24126223

  4. 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.

  5. Promising Practices in Small High Schools. A Report of 15 Northwest Projects.

    ERIC Educational Resources Information Center

    Northwest Regional Educational Lab., Portland, OR.

    Promising methods utilized in small rural high schools to provide a wider range of experiences for students are identified and described. Programs reported on include the Arctic Nursing Program, Career Research Program, Contractual Study Program, Eye-opening Experience, Field Experience Program, Guitar and Folk Music Program, Individualized…

  6. Identifying Instructional Strategies Used to Design Mobile Learning in a Corporate Setting

    ERIC Educational Resources Information Center

    Jackson-Butler, Uletta

    2016-01-01

    The purpose of this qualitative embedded multiple case study was to describe what instructional strategies corporate instructional designers were using to design mobile learning and to understand from their experiences which instructional strategies they believed enhance learning. Participants were five instructional designers who were actively…

  7. Identifying and Prioritizing Implementation Barriers, Gaps, and Strategies Through the Nigeria Implementation Science Alliance: Getting to Zero in the Prevention of Mother-to-Child Transmission of HIV.

    PubMed

    Ezeanolue, Echezona E; Powell, Byron J; Patel, Dina; Olutola, Ayodotun; Obiefune, Michael; Dakum, Patrick; Okonkwo, Prosper; Gobir, Bola; Akinmurele, Timothy; Nwandu, Anthea; Torpey, Kwasi; Oyeledum, Bolanle; Aina, Muyiwa; Eyo, Andy; Oleribe, Obinna; Ibanga, Ikoedem; Oko, John; Anyaike, Chukwuma; Idoko, John; Aliyu, Muktar H; Sturke, Rachel; Watts, Heather; Siberry, George

    2016-08-01

    In 2013, Nigeria accounted for 15% of the 1.3 million pregnant women living with HIV in sub-Saharan Africa and 26% of new infections among children worldwide. Despite this, less than 20% of pregnant women in Nigeria received an HIV test during pregnancy, and only 23% of HIV-infected pregnant women received appropriate intervention following HIV diagnosis. This article reports findings from 2 structured group exercises conducted at the first Nigeria Implementation Science Alliance Conference to identify (1) barriers and research gaps related to prevention of mother-to-child transmission (PMTCT) and (2) potential strategies and interventions that could address PMTCT challenges. Two 1-hour structured group exercises were conducted with 10 groups of 14-15 individuals (n = 145), who were asked to brainstorm barriers and strategies and to rank their top 3 in each category. Data analysis eliminated duplicate responses and categorized each of the priorities along the HIV care continuum: HIV diagnosis, linkage to care, or retention in care. Participating stakeholders identified 20 unique barriers and research gaps related to PMTCT across the HIV continuum. Twenty-five unique interventions and implementation strategies were identified. Similar to the barriers and research gaps, these interventions and strategies were distributed across the HIV care continuum. The barriers and strategies identified in this study represent important pathways to progress addressing MTCT. The deliberate involvement of state and federal policy makers, program implementers, and researchers helps ensure that they are relevant and actionable.

  8. 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

  9. Coalitional game theory as a promising approach to identify candidate autism genes.

    PubMed

    Gupta, Anika; Sun, Min Woo; Paskov, Kelley Marie; Stockham, Nate Tyler; Jung, Jae-Yoon; Wall, Dennis Paul

    2018-01-01

    Despite mounting evidence for the strong role of genetics in the phenotypic manifestation of Autism Spectrum Disorder (ASD), the specific genes responsible for the variable forms of ASD remain undefined. ASD may be best explained by a combinatorial genetic model with varying epistatic interactions across many small effect mutations. Coalitional or cooperative game theory is a technique that studies the combined effects of groups of players, known as coalitions, seeking to identify players who tend to improve the performance--the relationship to a specific disease phenotype--of any coalition they join. This method has been previously shown to boost biologically informative signal in gene expression data but to-date has not been applied to the search for cooperative mutations among putative ASD genes. We describe our approach to highlight genes relevant to ASD using coalitional game theory on alteration data of 1,965 fully sequenced genomes from 756 multiplex families. Alterations were encoded into binary matrices for ASD (case) and unaffected (control) samples, indicating likely gene-disrupting, inherited mutations in altered genes. To determine individual gene contributions given an ASD phenotype, a "player" metric, referred to as the Shapley value, was calculated for each gene in the case and control cohorts. Sixty seven genes were found to have significantly elevated player scores and likely represent significant contributors to the genetic coordination underlying ASD. Using network and cross-study analysis, we found that these genes are involved in biological pathways known to be affected in the autism cases and that a subset directly interact with several genes known to have strong associations to autism. These findings suggest that coalitional game theory can be applied to large-scale genomic data to identify hidden yet influential players in complex polygenic disorders such as autism.

  10. Long-Term Priming by Three Small Molecules Is a Promising Strategy for Enhancing Late Endothelial Progenitor Cell Bioactivities.

    PubMed

    Kim, Yeon-Ju; Ji, Seung Taek; Kim, Da Yeon; Jung, Seok Yun; Kang, Songhwa; Park, Ji Hye; Jang, Woong Bi; Yun, Jisoo; Ha, Jongseong; Lee, Dong Hyung; Kwon, Sang-Mo

    2018-06-12

    Endothelial progenitor cells (EPCs) and outgrowth endothelial cells (OECs) play a pivotal role in vascular regeneration in ischemic tissues; however, their therapeutic application in clinical settings is limited due to the low quality and quantity of patient-derived circulating EPCs. To solve this problem, we evaluated whether three priming small molecules (tauroursodeoxycholic acid, fucoidan, oleuropein) could enhance the angiogenic potential of EPCs. Such enhancement would promote the cellular bioactivities and help to develop functionally improved EPC therapeutics for ischemic diseases by accelerating the priming effect of the defined physiological molecules. We found that preconditioning of each of the three small molecules significantly induced the differentiation potential of CD34+ stem cells into EPC lineage cells. Notably, long-term priming of OECs with the three chemical cocktail (OEC-3C) increased the proliferation potential of EPCs via ERK activation. The migration, invasion, and tube-forming capacities were also significantly enhanced in OEC-3Cs compared with unprimed OECs. Further, the cell survival ratio was dramatically increased in OEC-3Cs against H2O2-induced oxidative stress via the augmented expression of Bcl-2, a prosurvival protein. In conclusion, we identified three small molecules for enhancing the bioactivities of ex vivo-expanded OECs for vascular repair. Long-term 3C priming might be a promising methodology for EPC-based therapy against ischemic diseases.

  11. Gene Manipulation Strategies to Identify Molecular Regulators of Axon Regeneration in the Central Nervous System

    PubMed Central

    Ribas, Vinicius T.; Costa, Marcos R.

    2017-01-01

    Limited axon regeneration in the injured adult mammalian central nervous system (CNS) usually results in irreversible functional deficits. Both the presence of extrinsic inhibitory molecules at the injury site and the intrinsically low capacity of adult neurons to grow axons are responsible for the diminished capacity of regeneration in the adult CNS. Conversely, in the embryonic CNS, neurons show a high regenerative capacity, mostly due to the expression of genes that positively control axon growth and downregulation of genes that inhibit axon growth. A better understanding of the role of these key genes controlling pro-regenerative mechanisms is pivotal to develop strategies to promote robust axon regeneration following adult CNS injury. Genetic manipulation techniques have been widely used to investigate the role of specific genes or a combination of different genes in axon regrowth. This review summarizes a myriad of studies that used genetic manipulations to promote axon growth in the injured CNS. We also review the roles of some of these genes during CNS development and suggest possible approaches to identify new candidate genes. Finally, we critically address the main advantages and pitfalls of gene-manipulation techniques, and discuss new strategies to promote robust axon regeneration in the mature CNS. PMID:28824380

  12. Identifying the trends in wound-healing patents for successful investment strategies

    PubMed Central

    Gwak, Jae Ha

    2017-01-01

    Background Recently, the need for rapid wound-healing has significantly increased because of the increasing number of patients who are diagnosed with diabetes and obesity. These conditions have contributed to a surge in the number of patients with chronic wounds worldwide. Furthermore, many cost-effective wound-healing technologies have been developed in order to keep up with the increased demand. In this paper, we performed a quantitative study of the trends associated with wound-healing technologies using patent data. Methodology We analyzed the trends considering four different groups of patent applicants: firms, universities, research institutes, and individuals using a structural topic model. In addition, we analyzed the knowledge flow between patent applicants using citation analysis, and confirmed the role of applicants in the knowledge-flow network using k-means clustering. As a result, the primary wound-healing technology patents applied for by the four groups varied considerably, and we classified the roles of patent applicants were found in the knowledge-flow network. Conclusions Our results showed the organizations that are leading each area of wound-healing technology. Furthermore, from the results, we identified specific institutions that are efficient for spreading knowledge related to wound-healing technology based on the patents. This information can contribute to the planning of investment strategies and technology policies related to wound-healing. PMID:28306732

  13. 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.

  14. IARC classes 1 and 2 carcinogens are successfully identified by an alternative strategy that detects DNA-reactivity and cell transformation ability of chemicals.

    PubMed

    Benigni, Romualdo; Bossa, Cecilia; Battistelli, Chiara Laura; Tcheremenskaia, Olga

    2013-12-12

    For decades, traditional toxicology has been the ultimate source of information on the carcinogenic potential of chemicals; however with increasing demand on regulation of chemicals and decreasing resources for testing, opportunities to accept "alternative" approaches have dramatically expanded. The need for tools able to identify carcinogens in shorter times and at a lower cost in terms of animal lives and money is still an open issue, and the present strategies and regulations for carcinogenicity pre-screening do not adequately protect human health. In previous papers, we have proposed an integrated in vitro/in silico strategy that detects DNA-reactivity and tissue disorganization/disruption by chemicals, and we have shown that the combination of Salmonella and Structural Alerts for the DNA-reactive carcinogens, and in vitro cell transformation assays for nongenotoxic carcinogens permits the identification of a very large proportion (up to 95%) of rodent carcinogens, while having a considerable specificity with the rodent noncarcinogens. In the present paper we expand the previous investigation and show that this alternative strategy identifies correctly IARC Classes 1 and 2 carcinogens. If implemented, this alternative strategy can contribute to improve the protection of human health while decreasing the use of animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. 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.

  16. Image is more than a uniform: the promise of assurance.

    PubMed

    Wocial, Lucia D; Sego, Kelly; Rager, Carrie; Laubersheimer, Shellee; Everett, Linda Q

    2014-05-01

    The purpose of this qualitative study was to explore the meaning of the phrase "image of the nurse" in the context of the desired brand experience of assurance. A brand is a promise that lives in the minds of consumers. Nurses play a key role in delivering on the brand promise of a hospital. Using focus groups, the authors applied a deductive approach to generate data. Discussion transcripts were analyzed by establishing codes and identifying themes. The most frequent comment from participants was that for nurses to communicate assurance, they must 1st be clean, well groomed, and understated in overall appearance. Nurse behaviors that reassure patients include being present with patients, helping patients know what to expect, and demonstrating a consistent team approach. Overall appearance and behaviors define the image of nurses and contribute significantly to the brand of assurance.

  17. 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

  18. National variety trials identify clones with high potential

    USDA-ARS?s Scientific Manuscript database

    Quality potato varieties are the backbone of a strong potato industry. Variety trials have been used to identify promising new varieties for well over a century. Trials are repeated and information collected over many years in order to confidently identify lines that may be well suited for productio...

  19. A New Strategy for Analyzing Time-Series Data Using Dynamic Networks: Identifying Prospective Biomarkers of Hepatocellular Carcinoma.

    PubMed

    Huang, Xin; Zeng, Jun; Zhou, Lina; Hu, Chunxiu; Yin, Peiyuan; Lin, Xiaohui

    2016-08-31

    Time-series metabolomics studies can provide insight into the dynamics of disease development and facilitate the discovery of prospective biomarkers. To improve the performance of early risk identification, a new strategy for analyzing time-series data based on dynamic networks (ATSD-DN) in a systematic time dimension is proposed. In ATSD-DN, the non-overlapping ratio was applied to measure the changes in feature ratios during the process of disease development and to construct dynamic networks. Dynamic concentration analysis and network topological structure analysis were performed to extract early warning information. This strategy was applied to the study of time-series lipidomics data from a stepwise hepatocarcinogenesis rat model. A ratio of lyso-phosphatidylcholine (LPC) 18:1/free fatty acid (FFA) 20:5 was identified as the potential biomarker for hepatocellular carcinoma (HCC). It can be used to classify HCC and non-HCC rats, and the area under the curve values in the discovery and external validation sets were 0.980 and 0.972, respectively. This strategy was also compared with a weighted relative difference accumulation algorithm (wRDA), multivariate empirical Bayes statistics (MEBA) and support vector machine-recursive feature elimination (SVM-RFE). The better performance of ATSD-DN suggests its potential for a more complete presentation of time-series changes and effective extraction of early warning information.

  20. A New Strategy for Analyzing Time-Series Data Using Dynamic Networks: Identifying Prospective Biomarkers of Hepatocellular Carcinoma

    NASA Astrophysics Data System (ADS)

    Huang, Xin; Zeng, Jun; Zhou, Lina; Hu, Chunxiu; Yin, Peiyuan; Lin, Xiaohui

    2016-08-01

    Time-series metabolomics studies can provide insight into the dynamics of disease development and facilitate the discovery of prospective biomarkers. To improve the performance of early risk identification, a new strategy for analyzing time-series data based on dynamic networks (ATSD-DN) in a systematic time dimension is proposed. In ATSD-DN, the non-overlapping ratio was applied to measure the changes in feature ratios during the process of disease development and to construct dynamic networks. Dynamic concentration analysis and network topological structure analysis were performed to extract early warning information. This strategy was applied to the study of time-series lipidomics data from a stepwise hepatocarcinogenesis rat model. A ratio of lyso-phosphatidylcholine (LPC) 18:1/free fatty acid (FFA) 20:5 was identified as the potential biomarker for hepatocellular carcinoma (HCC). It can be used to classify HCC and non-HCC rats, and the area under the curve values in the discovery and external validation sets were 0.980 and 0.972, respectively. This strategy was also compared with a weighted relative difference accumulation algorithm (wRDA), multivariate empirical Bayes statistics (MEBA) and support vector machine-recursive feature elimination (SVM-RFE). The better performance of ATSD-DN suggests its potential for a more complete presentation of time-series changes and effective extraction of early warning information.

  1. CD22: A Promising Target for Acute Lymphoblastic Leukemia Treatment | Center for Cancer Research

    Cancer.gov

    There are about 4,000 new cases of acute lymphoblastic leukemia (ALL) in the United States each year. Great improvements have been made in the treatment of ALL, but many patients suffer from side effects of standard therapy and continue to die of this disease. One of the most promising therapeutic strategies includes engineering T cells with a chimeric antigen receptor (CAR) that alters T cell specificity and function to recognize tumor antigens.

  2. 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

  3. 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.

  4. Keeping Our Students: Identifying Factors that Influence Student Withdrawal and Strategies to Enhance the Experience and Retention of First-Year Students

    ERIC Educational Resources Information Center

    Parmar, Deeba; Trotter, Eileen

    2004-01-01

    This article derives from local research at two UK universities as part of their institutional strategies to address retention and progression and enhance their students' experiences of higher education. In both Middlesex University and the University of Salford, research has been undertaken to identify factors which influence the retention and…

  5. Chromatographic fingerprinting as a strategy to identify regulated plants in illegal herbal supplements.

    PubMed

    Custers, D; Van Praag, N; Courselle, P; Apers, S; Deconinck, E

    2017-03-01

    Erectile dysfunction (ED) is a sexual disorder characterized by the inability to achieve or maintain a sufficiently rigid erection. Despite the availability of non-invasive oral treatment options, many patients turn to herbal alternatives. Furthermore, herbal supplements are increasingly gaining popularity in industrialized countries and, as a consequence, quality control is a highly important issue. Unfortunately, this is not a simple task since plants are often crushed and mixed with other plants, which complicates their identification by usage of classical approaches such as microscopy. The aim of this study was to explore the potential use of chromatographic fingerprinting to identify plants present in herbal preparations intended for the treatment of ED. To achieve this goal, a HPLC-PDA and a HPLC-MS method were developed, using a full factorial experimental design in order to acquire characteristic fingerprints of three plants which are potentially beneficial for treating ED: Epimedium spp., Pausinystalia yohimbe and Tribulus terrestris. The full factorial design demonstrated that for all three plant references a C8 column (250mm×4.6mm; 5µm particle size) is best suited; methanol and an ammonium formate buffer (pH 3) were found to be the best constituents for the mobile phase. The suitability of this strategy was demonstrated by analysing several self-made triturations in three different botanical matrices, which mimic the influential effects that could be expected when analysing herbal supplements. To conclude, this study demonstrates that chromatographic fingerprinting could provide a useful means to identify plants in a complex herbal mixture. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Career Education. Administrators and Counselors Implementation Model. Module III--Teacher Information and Orientation for Administrators. (3.1) Identify Change Strategy.

    ERIC Educational Resources Information Center

    Thompson, John A.; Chock, Mona K.O.

    Part of a 13-volume series designed to be used as a group inservice or a self-learning system to train school administrators and counselors for their role in career education, this section of module 3 is designed to identify change strategies to help the principal motivate teachers to accept the concept of career education. (Module 3 is one of six…

  7. 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.

  8. 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.

  9. 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.

  10. Identifying strategies to assist final semester nursing students to develop numeracy skills: a mixed methods study.

    PubMed

    Ramjan, Lucie M; Stewart, Lyn; Salamonson, Yenna; Morris, Maureen M; Armstrong, Lyn; Sanchez, Paula; Flannery, Liz

    2014-03-01

    It remains a grave concern that many nursing students within tertiary institutions continue to experience difficulties with achieving medication calculation competency. In addition, universities have a moral responsibility to prepare proficient clinicians for graduate practice. This requires risk management strategies to reduce adverse medication errors post registration. To identify strategies and potential predictors that may assist nurse academics to tailor their drug calculation teaching and assessment methods. This project builds on previous experience and explores students' perceptions of newly implemented interventions designed to increase confidence and competence in medication calculation. This mixed method study surveyed students (n=405) enrolled in their final semester of study at a large, metropolitan university in Sydney, Australia. Tailored, contextualised interventions included online practice quizzes, simulated medication calculation scenarios developed for clinical practice classes, contextualised 'pen and paper' tests, visually enhanced didactic remediation and 'hands-on' contextualised workshops. Surveys were administered to students to determine their perceptions of interventions and to identify whether these interventions assisted with calculation competence. Test scores were analysed using SPSS v. 20 for correlations between students' perceptions and actual performance. Qualitative open-ended survey questions were analysed manually and thematically. The study reinforced that nursing students preferred a 'hands-on,' contextualised approach to learning that was 'authentic' and aligned with clinical practice. Our interventions assisted with supporting students' learning and improvement of calculation confidence. Qualitative data provided further insight into students' awareness of their calculation errors and preferred learning styles. Some of the strongest predictors for numeracy skill performance included (1) being an international student, (2

  11. Identifying Proactive Collaboration Strategies for Teacher Readiness for Marginalized Students

    ERIC Educational Resources Information Center

    Akin, Imani; Neumann, Crystal

    2013-01-01

    This research discusses the value of collaborating to develop strategies that enhance teacher readiness for the marginalized student and the use of qualitative data that can lead to student academic and social success. Education domains include the learning environment, technology, and building parent and community connections. This research…

  12. 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.

  13. Strategies in Forecasting Outcomes in Ethical Decision-making: Identifying and Analyzing the Causes of the Problem

    PubMed Central

    Beeler, Cheryl K.; Antes, Alison L.; Wang, Xiaoqian; Caughron, Jared J.; Thiel, Chase E.; Mumford, Michael D.

    2010-01-01

    This study examined the role of key causal analysis strategies in forecasting and ethical decision-making. Undergraduate participants took on the role of the key actor in several ethical problems and were asked to identify and analyze the causes, forecast potential outcomes, and make a decision about each problem. Time pressure and analytic mindset were manipulated while participants worked through these problems. The results indicated that forecast quality was associated with decision ethicality, and the identification of the critical causes of the problem was associated with both higher quality forecasts and higher ethicality of decisions. Neither time pressure nor analytic mindset impacted forecasts or ethicality of decisions. Theoretical and practical implications of these findings are discussed. PMID:20352056

  14. 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.

  15. Achieving Literacy Excellence through Identifying and Utilizing High Yield Strategies

    ERIC Educational Resources Information Center

    Hardison, Ashley

    2017-01-01

    The purpose of this study was to delve into the literacy instructional strategies of selected high-performing K-2 teachers in a Clark County, Nevada school district. The study assessed the efficacy of teachers using five core literacy components: phonemic awareness, phonics, vocabulary, fluency, and comprehension for student achievement. High…

  16. Identifying potential environmental impacts of waste handling strategies in textile industry.

    PubMed

    Yacout, Dalia M M; Hassouna, M S

    2016-08-01

    Waste management is a successful instrument to minimize generated waste and improve environmental conditions. In spite of the large share of developing countries in the textile industry, limited information is available concerning the waste management strategies implemented for textiles on those countries and their environmental impacts. In the current study, two waste management approaches for hazardous solid waste treatment of acrylic fibers (landfill and incineration) were investigated. The main research questions were: What are the different impacts of each waste management strategy? Which waste management strategy is more ecofriendly? Life cycle assessment was employed in order to model the environmental impacts of each waste streaming approach separately then compare them together. Results revealed that incineration was the more ecofriendly approach. Highest impacts of both approaches were on ecotoxicity and carcinogenic potentials due to release of metals from pigment wastes. Landfill had an impact of 46.8 % on human health as compared to 28 % by incineration. Incineration impact on ecosystem quality was higher than landfill impact (68.4 and 51.3 %, respectively). As for resources category, incineration had a higher impact than landfill (3.5 and 2.0 %, respectively). Those impacts could be mitigated if state-of-the-art landfill or incinerator were used and could be reduced by applying waste to energy approaches for both management systems In conclusion, shifting waste treatment from landfill to incineration would decrease the overall environmental impacts and allow energy recovery. The potential of waste to energy approach by incineration with heat recovery could be considered in further studies. Future research is needed in order to assess the implementation of waste management systems and the preferable waste management strategies in the textile industry on developing countries.

  17. Identifying governance strategies that effectively support ecosystem services, resource sustainability, and biodiversity

    PubMed Central

    Kenward, R. E.; Whittingham, M. J.; Arampatzis, S.; Manos, B. D.; Hahn, T.; Terry, A.; Simoncini, R.; Alcorn, J.; Bastian, O.; Donlan, M.; Elowe, K.; Franzén, F.; Karacsonyi, Z.; Larsson, M.; Manou, D.; Navodaru, I.; Papadopoulou, O.; Papathanasiou, J.; von Raggamby, A.; Sharp, R. J. A.; Söderqvist, T.; Soutukorva, Å.; Vavrova, L.; Aebischer, N. J.; Leader-Williams, N.; Rutz, C.

    2011-01-01

    Conservation scientists, national governments, and international conservation groups seek to devise, and implement, governance strategies that mitigate human impact on the environment. However, few studies to date have systematically investigated the performance of different systems of governance in achieving successful conservation outcomes. Here, we use a newly-developed analytic framework to conduct analyses of a suite of case studies, linking different governance strategies to standardized scores for delivering ecosystem services, achieving sustainable use of natural resources, and conserving biodiversity, at both local and international levels. Our results: (i) confirm the benefits of adaptive management; and (ii) reveal strong associations for the role of leadership. Our work provides a critical step toward implementing empirically justified governance strategies that are capable of improving the management of human-altered environments, with benefits for both biodiversity and people. PMID:21402916

  18. 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.

  19. Strategies to prevent or reduce allergic disease.

    PubMed

    Prescott, Susan; Nowak-Węgrzyn, Anna

    2011-01-01

    The need for allergy prevention strategies has never been greater. Surging rates of food allergy and eczema are now adding to the already substantial burden of asthma and respiratory allergic diseases. The parallel rise in many other immune diseases suggests that the developing immune system is highly vulnerable to modern environmental changes. These strong environmental pressures may be one reason why simple allergen avoidance strategies have not been successful. Another more recent strategy to curtail the allergy epidemic has been to identify factors associated with modern lifestyle that may be causally linked with allergic disease, in an attempt to restore more favourable conditions for immune tolerance during early development. More hygienic conditions and disruption of microbial exposure have prompted strategies to restore this balance using probiotic and prebiotic supplements. Modern dietary changes linked with allergic diseases have prompted supplementation studies to assess the preventive merits of specific immunomodulatory dietary nutrients such as polyunsaturated fatty acids. Other nutrients such as antioxidants, folate, and vitamin D are also currently under investigation. Modern environmental pollutants have also been associated with adverse effects on immune development and the risk of disease. While many of these avenues have provided some promise, they have not yet translated into specific recommendations. Current evidence-based guidelines for allergy prevention remain limited to avoidance of cigarette smoke, promotion of breastfeeding and the use of hydrolysed formula when breastfeeding is not possible. Allergen avoidance strategies have been largely removed from most guidelines. It is hoped that a number of ongoing studies will help provide clearer recommendations around the use of probiotics, prebiotics, specific dietary nutrients and the role of early introduction of allergenic foods for the promotion of tolerance. Despite the current

  20. 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.

  1. Contexts for Promise: Noteworthy Practices and Innovations in the Identification of Gifted Students.

    ERIC Educational Resources Information Center

    Callahan, Carolyn M., Ed.; And Others

    This monograph contains 11 papers describing model projects that address the identification of gifted students. An introduction by Carolyn M. Callahan and Carol A. Tomlinson identifies commonalities and themes in the promising practices highlighted in the papers. The papers include: (1) "Project STREAM: Support, Training and Resources for…

  2. Sonographic Examination of The Fetus Vis-à-Vis Shoulder Dystocia: A Vexing Promise.

    PubMed

    Doty, Morgen S; Al-Hafez, Leen; Chauhan, Suneet P

    2016-12-01

    Since antepartum and intrapartum risk factors are poor at identifying women whose labor is complicated by shoulder dystocia, sonographic examination of the fetus holds promise. Though there are several measurements of biometric parameters to identify the parturient who will have shoulder dystocia, none are currently clinically useful. Three national guidelines confirm that sonographic measurements do not serve as appropriate diagnostic tests to identify women who will have shoulder dystocia with or without concurrent injury. In summary, biometric measurements of the fetus should not be used to alter clinical management with the aim of averting shoulder dystocia.

  3. Strategies for stroke rehabilitation.

    PubMed

    Dobkin, Bruce H

    2004-09-01

    Rehabilitation after hemiplegic stroke has typically relied on the training of patients in compensatory strategies. The translation of neuroscientific research into care has led to new approaches and renewed promise for better outcomes. Improved motor control can progress with task-specific training incorporating increased use of proximal and distal movements during intensive practice of real-world activities. Functional gains are incorrectly said to plateau by 3-6 months. Many patients retain latent sensorimotor function that can be realised any time after stroke with a pulse of goal-directed therapy. The amount of practice probably best determines gains for a given level of residual movement ability. Clinicians should encourage patients to build greater strength, speed, endurance, and precision of multijoint movements on tasks that increase independence and enrich daily activity. Imaging tools may help clinicians determine the capacity of residual networks to respond to a therapeutic approach and help establish optimal dose-response curves for training. Promising adjunct approaches include practice with robotic devices or in a virtual environment, electrical stimulation to increase cortical excitability during training, and drugs to optimise molecular mechanisms for learning. Biological strategies for neural repair may augment rehabilitation in the next decade.

  4. Strategies for stroke rehabilitation

    PubMed Central

    Dobkin, Bruce H

    2014-01-01

    Rehabilitation after hemiplegic stroke has typically relied on the training of patients in compensatory strategies. The translation of neuroscientific research into care has led to new approaches and renewed promise for better outcomes. Improved motor control can progress with task-specific training incorporating increased use of proximal and distal movements during intensive practice of real-world activities. Functional gains are incorrectly said to plateau by 3–6 months. Many patients retain latent sensorimotor function that can be realised any time after stroke with a pulse of goal-directed therapy. The amount of practice probably best determines gains for a given level of residual movement ability. Clinicians should encourage patients to build greater strength, speed, endurance, and precision of multijoint movements on tasks that increase independence and enrich daily activity. Imaging tools may help clinicians determine the capacity of residual networks to respond to a therapeutic approach and help establish optimal dose-response curves for training. Promising adjunct approaches include practice with robotic devices or in a virtual environment, electrical stimulation to increase cortical excitability during training, and drugs to optimise molecular mechanisms for learning. Biological strategies for neural repair may augment rehabilitation in the next decade. PMID:15324721

  5. 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

  6. 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

  7. A promising new thermoelectric material - Ruthenium silicide

    NASA Technical Reports Server (NTRS)

    Vining, Cronin B.; Mccormack, Joseph A.; Zoltan, Andrew; Zoltan, Leslie D.

    1991-01-01

    Experimental and theoretical efforts directed toward increasing thermoelectric figure of merit values by a factor of 2 or 3 have been encouraging in several respects. An accurate and detailed theoretical model developed for n-type silicon-germanium (SiGe) indicates that ZT values several times higher than currently available are expected under certain conditions. These new, high ZT materials are expected to be significantly different from SiGe, but not unreasonably so. Several promising candidate materials have been identified which may meet the conditions required by theory. One such candidate, ruthenium silicide, currently under development at JPL, has been estimated to have the potential to exhibit figure of merit values 4 times higher than conventional SiGe materials. Recent results are summarized.

  8. Multiple strategies to identify HIV-positive black men who have sex with men and transgender women in New York City: a cross-sectional analysis of recruitment results.

    PubMed

    Franks, Julie; Mannheimer, Sharon B; Hirsch-Moverman, Yael; Hayes-Larson, Eleanor; Colson, Paul W; Ortega, Hugo; El-Sadr, Wafaa M

    2018-03-01

    Black men who have sex with men and transgender women are at high risk for HIV infection, but are more likely to be unaware of their infection or not in care for diagnosed HIV compared to other races. Respondent driven sampling has been advanced as a method to reach stigmatized and hidden populations for HIV testing. We compared strategies to recruit black, substance-using men who have sex with men and transgender women to identify newly diagnosed HIV infection, or those previously diagnosed but not in care. The STAR (Seek, Test, and Retain) study (ClinicalTrials.gov NCT01790360) used several recruitment strategies to identify black, substance-using men who have sex with men and transgender women with undiagnosed HIV infection or with previously diagnosed HIV infection but who were not in HIV care. Respondent-driven sampling, community-based recruitment and online advertising were used to recruit participants. Incentivized peer referral was integrated into all recruitment strategies. Participants completed interviewer-administered questionnaires and HIV testing. Demographic and HIV risk-related characteristics and recruitment strategy were summarized and stratified by HIV status. Associations were tested using Pearson's chi-squared, Fisher's exact, and Wilcoxon rank sum tests. Factors associated with HIV-positive diagnosis at p < 0.1 were included in a multivariable logistic regression model. From July 2012 through October 2015, the study enrolled 1929 participants; 96.3% men who have sex with men and 3.7% transgender women. Behavioural risk factors included recent condomless anal sex (55.6%) and recent substance use during sex (73.1%). HIV prevalence was 8.7%. In multivariable analysis, significant associations with HIV infection included being transgender; non-Hispanic black; gay/homosexual orientation; not homeless; and less likely to have insufficient income for necessities. Among recruitment strategies, respondent driven sampling was least effective in

  9. Making Something of It: The Untold Stories of Promising Black Males at a Predominately White Institution of Higher Education

    ERIC Educational Resources Information Center

    Funk, Michael Sean

    2012-01-01

    Promising Black males are an understudied and underserved population in the field of higher education. The purpose of this study was to understand how promising Black males define academic success and to identify the factors that affect academic success at a large predominately White public institutions of higher education located in the…

  10. 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

  11. A systems biology strategy to identify molecular mechanisms of action and protein indicators of traumatic brain injury.

    PubMed

    Yu, Chenggang; Boutté, Angela; Yu, Xueping; Dutta, Bhaskar; Feala, Jacob D; Schmid, Kara; Dave, Jitendra; Tawa, Gregory J; Wallqvist, Anders; Reifman, Jaques

    2015-02-01

    The multifactorial nature of traumatic brain injury (TBI), especially the complex secondary tissue injury involving intertwined networks of molecular pathways that mediate cellular behavior, has confounded attempts to elucidate the pathology underlying the progression of TBI. Here, systems biology strategies are exploited to identify novel molecular mechanisms and protein indicators of brain injury. To this end, we performed a meta-analysis of four distinct high-throughput gene expression studies involving different animal models of TBI. By using canonical pathways and a large human protein-interaction network as a scaffold, we separately overlaid the gene expression data from each study to identify molecular signatures that were conserved across the different studies. At 24 hr after injury, the significantly activated molecular signatures were nonspecific to TBI, whereas the significantly suppressed molecular signatures were specific to the nervous system. In particular, we identified a suppressed subnetwork consisting of 58 highly interacting, coregulated proteins associated with synaptic function. We selected three proteins from this subnetwork, postsynaptic density protein 95, nitric oxide synthase 1, and disrupted in schizophrenia 1, and hypothesized that their abundance would be significantly reduced after TBI. In a penetrating ballistic-like brain injury rat model of severe TBI, Western blot analysis confirmed our hypothesis. In addition, our analysis recovered 12 previously identified protein biomarkers of TBI. The results suggest that systems biology may provide an efficient, high-yield approach to generate testable hypotheses that can be experimentally validated to identify novel mechanisms of action and molecular indicators of TBI. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

  12. Latino Immigrants, Acculturation, and Health: Promising New Directions in Research.

    PubMed

    Abraído-Lanza, Ana F; Echeverría, Sandra E; Flórez, Karen R

    2016-01-01

    This article provides an analysis of novel topics emerging in recent years in research on Latino immigrants, acculturation, and health. In the past ten years, the number of studies assessing new ways to conceptualize and understand how acculturation-related processes may influence health has grown. These new frameworks draw from integrative approaches testing new ground to acknowledge the fundamental role of context and policy. We classify the emerging body of evidence according to themes that we identify as promising directions--intrapersonal, interpersonal, social environmental, community, political, and global contexts, cross-cutting themes in life course and developmental approaches, and segmented assimilation--and discuss the challenges and opportunities each theme presents. This body of work, which considers acculturation in context, points to the emergence of a new wave of research that holds great promise in driving forward the study of Latino immigrants, acculturation, and health. We provide suggestions to further advance the ideologic and methodologic rigor of this new wave.

  13. Sphaeropsidin A shows promising activity against drug-resistant cancer cells by targeting regulatory volume increase.

    PubMed

    Mathieu, Véronique; Chantôme, Aurélie; Lefranc, Florence; Cimmino, Alessio; Miklos, Walter; Paulitschke, Verena; Mohr, Thomas; Maddau, Lucia; Kornienko, Alexander; Berger, Walter; Vandier, Christophe; Evidente, Antonio; Delpire, Eric; Kiss, Robert

    2015-10-01

    Despite the recent advances in the treatment of tumors with intrinsic chemotherapy resistance, such as melanoma and renal cancers, their prognosis remains poor and new chemical agents with promising activity against these cancers are urgently needed. Sphaeropsidin A, a fungal metabolite whose anticancer potential had previously received little attention, was isolated from Diplodia cupressi and found to display specific anticancer activity in vitro against melanoma and kidney cancer subpanels in the National Cancer Institute (NCI) 60-cell line screen. The NCI data revealed a mean LC50 of ca. 10 µM and a cellular sensitivity profile that did not match that of any other agent in the 765,000 compound database. Subsequent mechanistic studies in melanoma and other multidrug-resistant in vitro cancer models showed that sphaeropsidin A can overcome apoptosis as well as multidrug resistance by inducing a marked and rapid cellular shrinkage related to the loss of intracellular Cl(-) and the decreased HCO3 (-) concentration in the culture supernatant. These changes in ion homeostasis and the absence of effects on the plasma membrane potential were attributed to the sphaeropsidin A-induced impairment of regulatory volume increase (RVI). Preliminary results also indicate that depending on the type of cancer, the sphaeropsidin A effects on RVI could be related to Na-K-2Cl electroneutral cotransporter or Cl(-)/HCO3 (-) anion exchanger(s) targeting. This study underscores the modulation of ion-transporter activity as a promising therapeutic strategy to combat drug-resistant cancers and identifies the fungal metabolite, sphaeropsidin A, as a lead to develop anticancer agents targeting RVI in cancer cells.

  14. 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.

  15. 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.

  16. Identifying Strategic Scientific Opportunities

    Cancer.gov

    As NCI's central scientific strategy office, CRS collaborates with the institute's divisions, offices, and centers to identify research opportunities to advance NCI's vision for the future of cancer research.

  17. Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV.

    PubMed

    Wang, Xiaona; Wang, Li; Huang, Xuewei; Ma, Sunting; Yu, Meiling; Shi, Wen; Qiao, Xinyuan; Tang, Lijie; Xu, Yigang; Li, Yijing

    2017-10-25

    Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences ( p < 0.05) in the immune response levels were observed between probiotics expressing the COE-DCpep fusion protein and COE antigen alone, suggesting better immune efficiency of the probiotics vaccine expressing the DC-targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection.

  18. How might contact with nature promote human health? Promising mechanisms and a possible central pathway.

    PubMed

    Kuo, Ming

    2015-01-01

    How might contact with nature promote human health? Myriad studies have linked the two; at this time the task of identifying the mechanisms underlying this link is paramount. This article offers: (1) a compilation of plausible pathways between nature and health; (2) criteria for identifying a possible central pathway; and (3) one promising candidate for a central pathway. The 21 pathways identified here include environmental factors, physiological and psychological states, and behaviors or conditions, each of which has been empirically tied to nature and has implications for specific physical and mental health outcomes. While each is likely to contribute to nature's impacts on health to some degree and under some circumstances, this paper explores the possibility of a central pathway by proposing criteria for identifying such a pathway and illustrating their use. A particular pathway is more likely to be central if it can account for the size of nature's impacts on health, account for nature's specific health outcomes, and subsume other pathways. By these criteria, enhanced immune functioning emerges as one promising candidate for a central pathway between nature and health. There may be others.

  19. Strategy Instruction. ERIC Digest.

    ERIC Educational Resources Information Center

    Beckman, Pat

    This digest discusses using strategy instruction to assist students with learning disabilities. It begins by describing strategy instruction as teaching students about strategies, teaching them how and when to use strategies, helping students identify personally effective strategies, and encouraging students to make strategic behaviors part of…

  20. Promising behavior change techniques in a multicomponent intervention to reduce concerns about falls in old age: a Delphi study.

    PubMed

    Vestjens, Lotte; Kempen, Gertrudis I J M; Crutzen, Rik; Kok, Gerjo; Zijlstra, G A Rixt

    2015-04-01

    Complex behavior change interventions need evidence regarding the effectiveness of individual components to understand how these interventions work. The objective of this study was to identify the least and most promising behavior change techniques (BCTs) within the Dutch intervention 'A Matter of Balance' (AMB-NL) aimed at concerns about falls in old age as an example. After the identification of 27 BCTs within AMB-NL, an online two-round Delphi survey among 16 international experts was conducted to reach consensus on the least and most promising BCTs. The level of consensus and the level of importance of BCTs were determined. In total, 23 of the 27 (>85%) BCTs identified reached consensus. Most promising BCTs were goal setting (behavior), graded tasks and behavioral practice/rehearsal. Information about health consequences, salience of consequences and information about emotional consequences were considered least promising. These outcomes provide a first but important step in the evidence building process regarding the effectiveness of BCTs in a complex intervention. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. 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.

  2. 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.

  3. 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

  4. 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…

  5. Dopamine-assisted co-deposition: An emerging and promising strategy for surface modification.

    PubMed

    Qiu, Wen-Ze; Yang, Hao-Cheng; Xu, Zhi-Kang

    2018-04-27

    Mussel-inspired chemistry based on polydopamine (PDA) deposition has been developed as a facile and universal method for the surface modification of various materials. However, the inherent shortcomings of PDA coatings still impede their practical applications in the development of functional materials. In this review, we introduce the recent progress in the emerging dopamine-assisted co-deposition as a one-step strategy for functionalizing PDA-based coatings, and improving them in the aspects of deposition rate, morphology uniformity, surface wettability and chemical stability. The co-deposition mechanisms are categorized and discussed according to the interactions of dopamine or PDA with the introduced co-component. We also emphasize the influence of these interactions on the properties of the resultant PDA-based coatings. Meanwhile, we conclude the representative potential applications of those dopamine-assisted co-deposited coatings in material science, especially including separation membranes and biomaterials. Finally, some important issues and perspectives for theoretical study and applications are briefly discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Stop! Look & Lesson: A Guide to Identifying and Correcting Common Mathematical Errors Strategies.

    ERIC Educational Resources Information Center

    Palmer, Don; And Others

    This book provides a comprehensive collection of 66 teaching strategies and ideas to help overcome problems with number, each linked to a specific kind of error described in the related manual. Most of these strategies are classroom-ready and easily implemented. Some are notes for the teacher to read and then plan activities accordingly, and many…

  7. 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.

  8. Identifying e-cigarette vape stores: description of an online search methodology.

    PubMed

    Kim, Annice E; Loomis, Brett; Rhodes, Bryan; Eggers, Matthew E; Liedtke, Christopher; Porter, Lauren

    2016-04-01

    Although the overall impact of Electronic Nicotine Delivery Systems (ENDS) on public health is unclear, awareness, use, and marketing of the products have increased markedly in recent years. Identifying the increasing number of 'vape stores' that specialise in selling ENDS can be challenging given the lack of regulatory policies and licensing. This study assesses the utility of online search methods in identifying ENDS vape stores. We conducted online searches in Google Maps, Yelp, and YellowPages to identify listings of ENDS vape stores in Florida, and used a crowdsourcing platform to call and verify stores that primarily sold ENDS to consumers. We compared store listings generated from the online search and crowdsourcing methodology to list licensed tobacco and ENDS retailers from the Florida Department of Business and Professional Regulation. The combined results from all three online sources yielded a total of 403 ENDS vape stores. Nearly 32.5% of these stores were on the state tobacco licensure list, while 67.5% were not. Accuracy of online results was highest for Yelp (77.6%), followed by YellowPages (77.1%) and Google (53.0%). Using the online search methodology we identified more ENDS vape stores than were on the state tobacco licensure list. This approach may be a promising strategy to identify and track the growth of ENDS vape stores over time, especially in states without a systematic licensing requirement for such stores. 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/

  9. 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

  10. 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.

  11. 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.

  12. The Internship Divide: The Promise and Challenges of Internships in the Arts. Special Report

    ERIC Educational Resources Information Center

    Frenette, Alexandre

    2015-01-01

    The Strategic National Alumni Project (SNAAP)--an online survey, data management, and institutional improvement system designed to enhance the impact of arts-school education--brings much-needed nuance to assessing the promise and addressing the challenges of the intern economy. In particular, SNAAP data help participants identify historical…

  13. Diagnosing climate change impacts and identifying adaptation strategies by involving key stakeholder organisations and farmers in Sikkim, India: Challenges and opportunities.

    PubMed

    Azhoni, Adani; Goyal, Manish Kumar

    2018-06-01

    Narrowing the gap between research, policy making and implementing adaptation remains a challenge in many parts of the world where climate change is likely to severely impact water security. This research aims to narrow this gap by matching the adaptation strategies being framed by policy makers to that of the perspectives of development agencies, researchers and farmers in the Himalayan state of Sikkim in India. Our case study examined the perspectives of various stakeholders for climate change impacts, current adaptation strategies, knowledge gaps and adaptation barriers, particularly in the context of implementing the Sikkim State Action Plan on Climate Change through semi-structured interviews carried out with decision makers in the Sikkim State Government, researchers, consultants, local academia, development agencies and farmers. Using Stakeholders Network Analysis tools, this research unravels the complexities of perceiving climate change impacts, identifying strategies, and implementing adaptation. While farmers are less aware about the global phenomenon of climate change impacts for water security, their knowledge of the local conditions and their close interaction with the State Government Agriculture Department provides them opportunities. Although important steps are being initiated through the Sikkim State Action Plan on Climate Change it is yet to deliver effective means of adaptation implementation and hence, strengthening the networks of close coordination between the various implementing agencies will pay dividends. Knowledge gaps and the need for capacity building identified in this research, based on the understandings of key stakeholders are highly relevant to both the research community and for informing policy. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. 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

  15. Identifying Effective Strategies for Climate Change Education: The Coastal Areas Climate Change Education (CACCE) Partnership Audiences and Activities

    NASA Astrophysics Data System (ADS)

    Ryan, J. G.; Feldman, A.; Muller-Karger, F. E.; Gilbes, F.; Stone, D.; Plank, L.; Reynolds, C. J.

    2011-12-01

    Many past educational initiatives focused on global climate change have foundered on public skepticism and disbelief. Some key reasons for these past failures can be drawn directly from recognized best practices in STEM education - specifically, the necessity to help learners connect new knowledge with their own experiences and perspectives, and the need to create linkages with issues or concerns that are both important for and relevant to the audiences to be educated. The Coastal Areas Climate Change Education (CACCE) partnership has sought to follow these tenets as guiding principles in identifying critical audiences and developing new strategies for educating the public living in the low-lying coastal areas of Florida and the Caribbean on the realities, risks, and adaptation and mitigation strategies for dealing with the regional impacts of global climate change. CACCE is currently focused on three key learner audiences: a) The formal education spectrum, targeting K-12 curricula through middle school marine science courses, and student and educator audiences through coursework and participatory research strategies engaging participants in a range of climate-related investigations. b) Informal science educators and outlets, in particular aquaria and nature centers, as an avenue toward K-12 teacher professional development as well as for public education. c) Regional planning, regulatory and business professionals focused on the built environment along the coasts, many of whom require continuing education to maintain licensing and/or other professional certifications. Our current activities are focused on bringing together an effective set of educational, public- and private-sector partners to target the varied needs of these audiences in Florida and the U.S. Caribbean, and tailoring an educational plan aimed at these stakeholder audiences that starts with the regionally and topically relevant impacts of climate change, and strategies for effective adaptation and

  16. 76 FR 55889 - Reopening Notice: Promise Neighborhoods Program-Implementation Grant Competition; Promise...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... AGENCY: Office of Innovation and Improvement, Department of Education. ACTION: Notice. SUMMARY: The Department of Education (Department) reopens the competition for transmittal of applications for new awards... DEPARTMENT OF EDUCATION [CFDA Numbers 84.215N; 84.215P] Reopening Notice: Promise Neighborhoods...

  17. 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.

  18. 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…

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. A model-based assessment of the cost-utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients.

    PubMed

    Snowsill, Tristan; Huxley, Nicola; Hoyle, Martin; Jones-Hughes, Tracey; Coelho, Helen; Cooper, Chris; Frayling, Ian; Hyde, Chris

    2015-04-25

    Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost-utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS. A decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum. All strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could outweigh

  5. Why Identify Gifted Children?

    ERIC Educational Resources Information Center

    Congdon, Peter

    1985-01-01

    Emphasizes need to systematically identify gifted children. Defines the term "gifted" and considers three groups in detail: children of high intelligence, children of high academic aptitude, and talented children. Offers strategy for educational diagnosis of gifted children. (DST)

  6. Children's understanding of promising, lying, and false belief.

    PubMed

    Maas, Fay K

    2008-07-01

    Understanding promising and lying requires an understanding of intention and the ability to interpret mental states. The author examined (a) the extent to which 4- to 6-year-olds focus on the sincerity of the speaker's intention when the 4-to 6-year-olds make judgments about promises and lies and (b) whether false-belief reasoning skills are related to understanding promising and lying. Participants watched videotaped stories and made promise and lie judgments from their own perspective and from the listener-character's perspective. Children also completed false-belief reasoning tasks. Older children made more correct promise judgments from both perspectives. All children made correct lie judgments from the listener's perspective. The author found that Ist-order false-belief reasoning was related to making judgments from the participant's perspective; 2nd-order false-belief reasoning was related to making judgments from the listener-character's perspective. Results suggest that children's understanding of promising and lying moves from a focus on outcome toward a focus on the belief that each utterance is designed to create.

  7. Gravitational-wave astronomy: delivering on the promises

    NASA Astrophysics Data System (ADS)

    Schutz, B. F.

    2018-05-01

    Now that LIGO and Virgo have begun to detect gravitational-wave events with regularity, the field of gravitational-wave astronomy is beginning to realize its promise. Binary black holes and, very recently, binary neutron stars have been observed, and we are already learning much from them. The future, with improved sensitivity, more detectors and detectors like LISA in different frequency bands, has even more promise to open a completely hidden side of the Universe to our exploration. This article is part of a discussion meeting issue `The promises of gravitational-wave astronomy'.

  8. 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…

  9. 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.

  10. 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.

  11. 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.

  12. Oleaginous yeasts: Promising platforms for the production of oleochemicals and biofuels.

    PubMed

    Adrio, José L

    2017-09-01

    Oleaginous yeasts have a unique physiology that makes them the best suited hosts for the production of lipids, oleochemicals, and diesel-like fuels. Their high lipogenesis, capability of growing on many different carbon sources (including lignocellulosic sugars), easy large-scale cultivation, and an increasing number of genetic tools are some of the advantages that have encouraged their use to develop sustainable processes. This mini-review summarizes the metabolic engineering strategies developed in oleaginous yeasts within the last 2 years to improve process metrics (titer, yield, and productivity) for the production of lipids, free fatty acids, fatty acid-based chemicals (e.g., fatty alcohols, fatty acid ethyl esters), and alkanes. During this short period of time, tremendous progress has been made in Yarrowia lipolytica, the model oleaginous yeast, which has been engineered to improve lipid production by different strategies including increasing lipogenic pathway flux and biosynthetic precursors, and blocking degradation pathways. Moreover, remarkable advances have also been reported in Rhodosporidium toruloides and Lipomyces starkey despite the limited genetic tools available for these two very promising hosts. Biotechnol. Bioeng. 2017;114: 1915-1920. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Harnessing the Promise of Moral Distress: A Call for Re-Orientation.

    PubMed

    Carse, Alisa; Rushton, Cynda Hylton

    2017-01-01

    Despite over three decades of research into the sources and costs of what has become an "epidemic" of moral distress among healthcare professionals, spanning many clinical disciplines and roles, there has been little significant progress in effectively addressing moral distress. We believe the persistent sense of frustration, helplessness, and despair still dominating the clinical moral distress narrative signals a need for re-orientation in the way moral distress is understood and worked with. Most fundamentally, moral distress reveals moral investment and energy. It is the troubled call of conscience, an expression of fidelity to moral commitments seen as imperiled or compromised. It is crucial that we find ways to empower clinicians in heeding this call-to support clinicians' moral agency and voice, foster their moral resilience, and facilitate their ability to contribute to needed reform within the organizations and systems in which they work. These objectives must inform creative expansion in the design of strategies for addressing moral distress in the day-to-day of clinical practice. We include suggestions about promising directions such strategies might take in the hope of spurring further innovation within clinical environments. Copyright 2016 The Journal of Clinical Ethics. All rights reserved.

  14. 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.

  15. Simultaneous co-fermentation of mixed sugars: a promising strategy for producing cellulosic ethanol.

    PubMed

    Kim, Soo Rin; Ha, Suk-Jin; Wei, Na; Oh, Eun Joong; Jin, Yong-Su

    2012-05-01

    The lack of microbial strains capable of fermenting all sugars prevalent in plant cell wall hydrolyzates to ethanol is a major challenge. Although naturally existing or engineered microorganisms can ferment mixed sugars (glucose, xylose and galactose) in these hydrolyzates sequentially, the preferential utilization of glucose to non-glucose sugars often results in lower overall yield and productivity of ethanol. Therefore, numerous metabolic engineering approaches have been attempted to construct optimal microorganisms capable of co-fermenting mixed sugars simultaneously. Here, we present recent findings and breakthroughs in engineering yeast for improved ethanol production from mixed sugars. In particular, this review discusses new sugar transporters, various strategies for simultaneous co-fermentation of mixed sugars, and potential applications of co-fermentation for producing fuels and chemicals. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. 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

  17. 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.

  18. Performance of Risk-Based and Birth-Cohort Strategies for Identifying Hepatitis C Virus Infection Among People Entering Prison, Wisconsin, 2014.

    PubMed

    Stockman, Lauren J; Greer, James; Holzmacher, Ryan; Dittmann, Beth; Hoftiezer, Scott A; Alsum, Lori E; Prieve, Audrey; Westergaard, Ryan P; Guilfoyle, Sheila M; Vergeront, James M

    2016-01-01

    The prevalence of hepatitis C virus (HCV) infection among young adults is rising in Wisconsin. We examined the prevalence of HCV infection among male and female inmates entering two Wisconsin prisons and evaluated existing and alternate risk-based strategies for identifying HCV infection at intake. We added HCV testing to the intake procedures for all 1,239 adults prison entrants at the Wisconsin Department of Corrections (WDOC) from November 3, 2014, to January 31, 2015. We identified risk factors associated with HCV infection during the routine intake examination and calculated the sensitivity and specificity of risk-based testing strategies for identifying HCV infection. The prevalence of HCV antibody among prison entrants was 12.5% (95% confidence interval [CI] 10.7, 14.4) overall and was almost two times higher at the women's facility (21.3%, 95% CI 15.4, 27.2) than at the men's facility (11.0%, 95% CI 0.0, 12.9) (p<0.001). The sensitivity and specificity of the WDOC risk-based criteria were 88% (95% CI 83, 93) and 80% (95% CI 78, 83), respectively. Adding a new criterion, the 1945-1965 birth cohort, to the risk-based criteria improved the sensitivity to 92% (95% CI 88, 96) and lowered the specificity to 71% (95% CI 68, 74). Compared with entrants without these risk factors, HCV antibody prevalence was significantly higher among prison entrants who had the following risk factors: injection drug use (prevalence ratio [PR] = 9.9, 95% CI 7.4, 13.2), liver disease (PR=9.7, 95% CI 7.8, 12.0), and elevated levels of alanine transaminase (PR=3.6, 95% CI 2.7, 4.9). The WDOC risk criteria for HCV testing identified 88% of HCV infections among prison entrants. Including the 1945-1965 birth cohort as a criterion along with the other WDOC risk criteria increased the sensitivity of targeted testing to 92%. These findings may be informative to jurisdictions where universal HCV testing is not feasible because of resource limitations.

  19. Development of a strategy to identify gastrointestinal epithelial membrane proteins induced by irradiation

    NASA Astrophysics Data System (ADS)

    Griffin, Kathleen P.

    up to 34 % and 17 % respectively. These findings, and the fact that cell growth was blocked by the addition of 1 muM of the K[ATP] specific inhibitor glibenclamide, suggest that KATP functions in the growth and/or survival of the intestinal epithelium and thus may provide a new target for mucositis therapies. This action of K[ATP], along with the detection of an additional target (CFTR) that has since been implicated in the gastrointestinal radiation response by others, shows that the strategy adopted in this thesis was successful in identifying modulators of gastrointestinal epithelial cell function.

  20. Borophene as a Promising Material for Charge-Modulated Switchable CO2 Capture.

    PubMed

    Tan, Xin; Tahini, Hassan A; Smith, Sean C

    2017-06-14

    Ideal carbon dioxide (CO 2 ) capture materials for practical applications should bind CO 2 molecules neither too weakly to limit good loading kinetics nor too strongly to limit facile release. Although charge-modulated switchable CO 2 capture has been proposed to be a controllable, highly selective, and reversible CO 2 capture strategy, the development of a practical gas-adsorbent material remains a great challenge. In this study, by means of density functional theory (DFT) calculations, we have examined the possibility of conductive borophene nanosheets as promising sorbent materials for charge-modulated switchable CO 2 capture. Our results reveal that the binding strength of CO 2 molecules on negatively charged borophene can be significantly enhanced by injecting extra electrons into the adsorbent. At saturation CO 2 capture coverage, the negatively charged borophene achieves CO 2 capture capacities up to 6.73 × 10 14 cm -2 . In contrast to the other CO 2 capture methods, the CO 2 capture/release processes on negatively charged borophene are reversible with fast kinetics and can be easily controlled via switching on/off the charges carried by borophene nanosheets. Moreover, these negatively charged borophene nanosheets are highly selective for separating CO 2 from mixtures with CH 4 , H 2 , and/or N 2 . This theoretical exploration will provide helpful guidance for identifying experimentally feasible, controllable, highly selective, and high-capacity CO 2 capture materials with ideal thermodynamics and reversibility.

  1. Phytoremediation of Polychlorinated Biphenyls: New Trends and Promises

    PubMed Central

    Van Aken, Benoit; Correa, Paola A.; Schnoor, Jerald L.

    2011-01-01

    Transgenic plants and associated bacteria constitute a new generation of genetically modified organisms for efficient and environmental-friendly treatment of soil and water contaminated with polychlorinated biphenyls (PCBs). This review focuses on recent advances in phytoremediation for the treatment of PCBs, including the development of transgenic plants and associated bacteria. Phytoremediation, or the use of higher plants for rehabilitation of soil and groundwater, is a promising strategy for cost-effective treatment of sites contaminated by toxic compounds, including toxic PCBs. Plants can help mitigate environmental pollution by PCBs through a range of mechanisms: besides uptake from soil (phytoextraction), plants are capable of enzymatic transformation of PCBs (phytotransformation); by releasing a variety of secondary metabolites, plants also enhance the microbial activity in the root zone, improving biodegradation of PCBs (rhizoremediation). However, because of their hydrophobicity and chemical stability, PCBs are only slowly taken up and degraded by plants and associated bacteria, resulting in incomplete treatment and potential release of toxic metabolites into the environment. Moreover, naturally occurring plant-associated bacteria may not possess the enzymatic machinery necessary for PCB degradation. In order to overcome these limitations, bacterial genes involved in the metabolism of PCBs, such as biphenyl dioxygenases, have been introduced into higher plants, following a strategy similar to the development of transgenic crops. Similarly, bacteria have then been genetically modified that exhibit improved biodegradation capabilities and are able to maintain stable relationships with plants. Transgenic plants and associated bacteria bring hope for a broader and more efficient application of phytoremediation for the treatment of PCBs. PMID:20384372

  2. 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

  3. VLSI Technology: Impact and Promise. Identifying Emerging Issues and Trends in Technology for Special Education.

    ERIC Educational Resources Information Center

    Bayoumi, Magdy

    As part of a 3-year study to identify emerging issues and trends in technology for special education, this paper addresses the implications of very large scale integrated (VLSI) technology. The first section reviews the development of educational technology, particularly microelectronics technology, from the 1950s to the present. The implications…

  4. Targeting Tumor Microenvironment with Silibinin: Promise and Potential for a Translational Cancer Chemopreventive Strategy

    PubMed Central

    Deep, Gagan; Agarwal, Rajesh

    2014-01-01

    Tumor microenvironment (TME) refers to the dynamic cellular and extra-cellular components surrounding tumor cells at each stage of the carcinogenesis. TME has now emerged as an integral and inseparable part of the carcinogenesis that plays a critical role in tumor growth, angiogenesis, epithelial to mesenchymal transition (EMT), invasion, migration and metastasis. Besides its vital role in carcinogenesis, TME is also a better drug target because of its relative genetic stability with lesser probability for the development of drug-resistance. Several drugs targeting the TME (endothelial cells, macrophages, cancer-associated fibroblasts, or extra-cellular matrix) have either been approved or are in clinical trials. Recently, non-steroidal anti-inflammatory drugs targeting inflammation were reported to also prevent several cancers. These exciting developments suggest that cancer chemopreventive strategies targeting both tumor and TME would be better and effective towards preventing, retarding or reversing the process of carcinogenesis. Here, we have reviewed the effect of a well established hepatoprotective and chemopreventive agent silibinin on cellular (endothelial, fibroblast and immune cells) and non-cellular components (cytokines, growth factors, proteinases etc.) of the TME. Silibinin targets TME constituents as well as their interaction with cancer cells, thereby inhibiting tumor growth, angiogenesis, inflammation, EMT, and metastasis. Silibinin is already in clinical trials, and based upon completed studies we suggest that its chemopreventive effectiveness should be verified through its effect on biological end points in both tumor and TME. Overall, we believe that the chemopreventive strategies targeting both tumor and TME have practical and translational utility in lowering the cancer burden. PMID:23617249

  5. The Promise of Mesenchymal Stem Cell Therapy for Diabetic Kidney Disease.

    PubMed

    Griffin, Tomás P; Martin, William Patrick; Islam, Nahidul; O'Brien, Timothy; Griffin, Matthew D

    2016-05-01

    Diabetes mellitus (DM) commonly leads to progressive chronic kidney disease despite current best medical practice. The pathogenesis of diabetic kidney disease (DKD) involves a complex network of primary and secondary mechanisms with both intra-renal and systemic components. Apart from inhibition of the renin angiotensin aldosterone system, targeting individual pathogenic mediators with drug therapy has not, thus far, been proven to have high clinical value. Stem or progenitor cell therapies offer an alternative strategy for modulating complex disease processes through suppressing multiple pathogenic pathways and promoting pro-regenerative mechanisms. Mesenchymal stem cells (MSCs) have shown particular promise based on their accessibility from adult tissues and their diverse mechanisms of action including secretion of paracrine anti-inflammatory and cyto-protective factors. In this review, the progress toward clinical translation of MSC therapy for DKD is critically evaluated. Results from animal models suggest distinct potential for systemic MSC infusion to favourably modulate DKD progression. However, only a few early phase clinical trials have been initiated and efficacy in humans remains to be proven. Key knowledge gaps and research opportunities exist in this field. These include the need to gain greater understanding of in vivo mechanism of action, to identify quantifiable biomarkers of response to therapy and to define the optimal source, dose and timing of MSC administration. Given the rising prevalence of DM and DKD worldwide, continued progress toward harnessing the inherent regenerative functions of MSCs and other progenitor cells for even a subset of those affected has potential for profound societal benefits.

  6. A strategy to discover new organizers identifies a putative heart organizer

    PubMed Central

    Anderson, Claire; Khan, Mohsin A. F.; Wong, Frances; Solovieva, Tatiana; Oliveira, Nidia M. M.; Baldock, Richard A.; Tickle, Cheryll; Burt, Dave W.; Stern, Claudio D.

    2016-01-01

    Organizers are regions of the embryo that can both induce new fates and impart pattern on other regions. So far, surprisingly few organizers have been discovered, considering the number of patterned tissue types generated during development. This may be because their discovery has relied on transplantation and ablation experiments. Here we describe a new approach, using chick embryos, to discover organizers based on a common gene expression signature, and use it to uncover the anterior intestinal portal (AIP) endoderm as a putative heart organizer. We show that the AIP can induce cardiac identity from non-cardiac mesoderm and that it can pattern this by specifying ventricular and suppressing atrial regional identity. We also uncover some of the signals responsible. The method holds promise as a tool to discover other novel organizers acting during development. PMID:27557800

  7. 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.

  8. Understanding the Promise: A Typology of State and Local College Promise Programs

    ERIC Educational Resources Information Center

    Perna, Laura W.; Leigh, Elaine W.

    2018-01-01

    Over the past decade, but especially in the past few years, programs with a "promise" label have been advanced at the local, state, and federal levels. To advance understanding of the design, implementation, and impact of the many different versions of emerging programs, policymakers, practitioners, and researchers need an organizing…

  9. 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…

  10. Tennessee Promise: A Response to Organizational Change

    ERIC Educational Resources Information Center

    Littlepage, Ben; Clark, Teresa; Wilson, Randal; Stout, Logan

    2018-01-01

    Community colleges in Tennessee, either directly or indirectly, experienced unprecedented change as a result of Tennessee Promise. The present study explored how student support service administrators at three community colleges responded to organizational change as a result of the Tennessee Promise legislation. Investigators selected community…

  11. Gravitational-wave astronomy: delivering on the promises.

    PubMed

    Schutz, B F

    2018-05-28

    Now that LIGO and Virgo have begun to detect gravitational-wave events with regularity, the field of gravitational-wave astronomy is beginning to realize its promise. Binary black holes and, very recently, binary neutron stars have been observed, and we are already learning much from them. The future, with improved sensitivity, more detectors and detectors like LISA in different frequency bands, has even more promise to open a completely hidden side of the Universe to our exploration.This article is part of a discussion meeting issue 'The promises of gravitational-wave astronomy'. © 2018 The Author(s).

  12. An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.

    PubMed

    Bonnet, Crystel; Riahi, Zied; Chantot-Bastaraud, Sandra; Smagghe, Luce; Letexier, Mélanie; Marcaillou, Charles; Lefèvre, Gaëlle M; Hardelin, Jean-Pierre; El-Amraoui, Aziz; Singh-Estivalet, Amrit; Mohand-Saïd, Saddek; Kohl, Susanne; Kurtenbach, Anne; Sliesoraityte, Ieva; Zobor, Ditta; Gherbi, Souad; Testa, Francesco; Simonelli, Francesca; Banfi, Sandro; Fakin, Ana; Glavač, Damjan; Jarc-Vidmar, Martina; Zupan, Andrej; Battelino, Saba; Martorell Sampol, Loreto; Claveria, Maria Antonia; Catala Mora, Jaume; Dad, Shzeena; Møller, Lisbeth B; Rodriguez Jorge, Jesus; Hawlina, Marko; Auricchio, Alberto; Sahel, José-Alain; Marlin, Sandrine; Zrenner, Eberhart; Audo, Isabelle; Petit, Christine

    2016-12-01

    Usher syndrome (USH), the most prevalent cause of hereditary deafness-blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1-3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.

  13. An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients

    PubMed Central

    Bonnet, Crystel; Riahi, Zied; Chantot-Bastaraud, Sandra; Smagghe, Luce; Letexier, Mélanie; Marcaillou, Charles; Lefèvre, Gaëlle M; Hardelin, Jean-Pierre; El-Amraoui, Aziz; Singh-Estivalet, Amrit; Mohand-Saïd, Saddek; Kohl, Susanne; Kurtenbach, Anne; Sliesoraityte, Ieva; Zobor, Ditta; Gherbi, Souad; Testa, Francesco; Simonelli, Francesca; Banfi, Sandro; Fakin, Ana; Glavač, Damjan; Jarc-Vidmar, Martina; Zupan, Andrej; Battelino, Saba; Martorell Sampol, Loreto; Claveria, Maria Antonia; Catala Mora, Jaume; Dad, Shzeena; Møller, Lisbeth B; Rodriguez Jorge, Jesus; Hawlina, Marko; Auricchio, Alberto; Sahel, José-Alain; Marlin, Sandrine; Zrenner, Eberhart; Audo, Isabelle; Petit, Christine

    2016-01-01

    Usher syndrome (USH), the most prevalent cause of hereditary deafness–blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1–3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods. PMID:27460420

  14. Safety huddles to proactively identify and address electronic health record safety

    PubMed Central

    Menon, Shailaja; Singh, Hardeep; Giardina, Traber D; Rayburn, William L; Davis, Brenda P; Russo, Elise M

    2017-01-01

    Objective: Methods to identify and study safety risks of electronic health records (EHRs) are underdeveloped and largely depend on limited end-user reports. “Safety huddles” have been found useful in creating a sense of collective situational awareness that increases an organization’s capacity to respond to safety concerns. We explored the use of safety huddles for identifying and learning about EHR-related safety concerns. Design: Data were obtained from daily safety huddle briefing notes recorded at a single midsized tertiary-care hospital in the United States over 1 year. Huddles were attended by key administrative, clinical, and information technology staff. We conducted a content analysis of huddle notes to identify what EHR-related safety concerns were discussed. We expanded a previously developed EHR-related error taxonomy to categorize types of EHR-related safety concerns recorded in the notes. Results: On review of daily huddle notes spanning 249 days, we identified 245 EHR-related safety concerns. For our analysis, we defined EHR technology to include a specific EHR functionality, an entire clinical software application, or the hardware system. Most concerns (41.6%) involved “EHR technology working incorrectly,” followed by 25.7% involving “EHR technology not working at all.” Concerns related to “EHR technology missing or absent” accounted for 16.7%, whereas 15.9% were linked to “user errors.” Conclusions: Safety huddles promoted discussion of several technology-related issues at the organization level and can serve as a promising technique to identify and address EHR-related safety concerns. Based on our findings, we recommend that health care organizations consider huddles as a strategy to promote understanding and improvement of EHR safety. PMID:28031286

  15. (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.

  16. Homosexuality in Turkey: strategies for managing heterosexism.

    PubMed

    Bakacak, Ayça Gelgeç; Oktem, Pinar

    2014-01-01

    The goal of this study was to identify the strategies used by young homosexuals to manage their sexual minority status in Turkey. In-depth interviews were conducted with 15 self-identified homosexual university students. The data on the strategies employed by homosexuals suggested a categorization of these strategies into four interrelated areas: strategies employed in the process of self-acceptance; strategies to manage sexual stigma and prejudice; strategies specific to the coming-out process; and the strategies used while openly expressing their sexual identities.

  17. Comparison of genome-wide selection strategies to identify furfural tolerance genes in Escherichia coli.

    PubMed

    Glebes, Tirzah Y; Sandoval, Nicholas R; Gillis, Jacob H; Gill, Ryan T

    2015-01-01

    Engineering both feedstock and product tolerance is important for transitioning towards next-generation biofuels derived from renewable sources. Tolerance to chemical inhibitors typically results in complex phenotypes, for which multiple genetic changes must often be made to confer tolerance. Here, we performed a genome-wide search for furfural-tolerant alleles using the TRackable Multiplex Recombineering (TRMR) method (Warner et al. (2010), Nature Biotechnology), which uses chromosomally integrated mutations directed towards increased or decreased expression of virtually every gene in Escherichia coli. We employed various growth selection strategies to assess the role of selection design towards growth enrichments. We also compared genes with increased fitness from our TRMR selection to those from a previously reported genome-wide identification study of furfural tolerance genes using a plasmid-based genomic library approach (Glebes et al. (2014) PLOS ONE). In several cases, growth improvements were observed for the chromosomally integrated promoter/RBS mutations but not for the plasmid-based overexpression constructs. Through this assessment, four novel tolerance genes, ahpC, yhjH, rna, and dicA, were identified and confirmed for their effect on improving growth in the presence of furfural. © 2014 Wiley Periodicals, Inc.

  18. Virtual High-Throughput Screening To Identify Novel Activin Antagonists

    PubMed Central

    Zhu, Jie; Mishra, Rama K.; Schiltz, Gary E.; Makanji, Yogeshwar; Scheidt, Karl A.; Mazar, Andrew P.; Woodruff, Teresa K.

    2015-01-01

    Activin belongs to the TGFβ superfamily, which is associated with several disease conditions, including cancer-related cachexia, preterm labor with delivery, and osteoporosis. Targeting activin and its related signaling pathways holds promise as a therapeutic approach to these diseases. A small-molecule ligand-binding groove was identified in the interface between the two activin βA subunits and was used for a virtual high-throughput in silico screening of the ZINC database to identify hits. Thirty-nine compounds without significant toxicity were tested in two well-established activin assays: FSHβ transcription and HepG2 cell apoptosis. This screening workflow resulted in two lead compounds: NUCC-474 and NUCC-555. These potential activin antagonists were then shown to inhibit activin A-mediated cell proliferation in ex vivo ovary cultures. In vivo testing showed that our most potent compound (NUCC-555) caused a dose-dependent decrease in FSH levels in ovariectomized mice. The Blitz competition binding assay confirmed target binding of NUCC-555 to the activin A:ActRII that disrupts the activin A:ActRII complex’s binding with ALK4-ECD-Fc in a dose-dependent manner. The NUCC-555 also specifically binds to activin A compared with other TGFβ superfamily member myostatin (GDF8). These data demonstrate a new in silico-based strategy for identifying small-molecule activin antagonists. Our approach is the first to identify a first-in-class small-molecule antagonist of activin binding to ALK4, which opens a completely new approach to inhibiting the activity of TGFβ receptor superfamily members. in addition, the lead compound can serve as a starting point for lead optimization toward the goal of a compound that may be effective in activin-mediated diseases. PMID:26098096

  19. Identifying Motivational Strategies to Engage Undergraduate Learning in Web-Based Instruction

    ERIC Educational Resources Information Center

    Glore, Peyton R.

    2010-01-01

    Increased access to the Internet and online technologies has allowed a growing number of students to take part in college courses online. Participants in these courses tend not to be as motivated to engage in learning with the same thoroughness as they do in a classroom-based course. This study investigates strategies that are perceived as…

  20. Computational analysis of antibody dynamics identifies recent HIV-1 infection.

    PubMed

    Seaton, Kelly E; Vandergrift, Nathan A; Deal, Aaron W; Rountree, Wes; Bainbridge, John; Grebe, Eduard; Anderson, David A; Sawant, Sheetal; Shen, Xiaoying; Yates, Nicole L; Denny, Thomas N; Liao, Hua-Xin; Haynes, Barton F; Robb, Merlin L; Parkin, Neil; Santos, Breno R; Garrett, Nigel; Price, Matthew A; Naniche, Denise; Duerr, Ann C; Keating, Sheila; Hampton, Dylan; Facente, Shelley; Marson, Kara; Welte, Alex; Pilcher, Christopher D; Cohen, Myron S; Tomaras, Georgia D

    2017-12-21

    Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1-infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation.

  1. Computational analysis of antibody dynamics identifies recent HIV-1 infection

    PubMed Central

    Seaton, Kelly E.; Vandergrift, Nathan A.; Deal, Aaron W.; Rountree, Wes; Anderson, David A.; Sawant, Sheetal; Shen, Xiaoying; Yates, Nicole L.; Denny, Thomas N.; Haynes, Barton F.; Robb, Merlin L.; Parkin, Neil; Santos, Breno R.; Price, Matthew A.; Naniche, Denise; Duerr, Ann C.; Hampton, Dylan; Facente, Shelley; Marson, Kara; Welte, Alex; Pilcher, Christopher D.; Cohen, Myron S.

    2017-01-01

    Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1–infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation. PMID:29263306

  2. Promise-based management: the essence of execution.

    PubMed

    Sull, Donald N; Spinosa, Charles

    2007-04-01

    Critical initiatives stall for a variety of reasons--employee disengagement, a lack of coordination between functions, complex organizational structures that obscure accountability, and so on. To overcome such obstacles, managers must fundamentally rethink how work gets done. Most of the challenges stem from broken or poorly crafted commitments. That's because every company is, at its heart, a dynamic network of promises made between employees and colleagues, customers, outsourcing partners, or other stakeholders. Executives can overcome many problems in the short-term and foster productive, reliable workforces for the long-term by practicing what the authors call "promise-based management," which involves cultivating and coordinating commitments in a systematic way. Good promises share five qualities: They are public, active, voluntary, explicit, and mission based. To develop and execute an effective promise, the "provider" and the "customer" in the deal should go through three phases of conversation. The first, achieving a meeting of minds, entails exploring the fundamental questions of coordinated effort: What do you mean? Do you understand what I mean? What should I do? What will you do? Who else should we talk to? In the next phase, making it happen, the provider executes on the promise. In the final phase, closing the loop, the customer publicly declares that the provider has either delivered the goods or failed to do so. Leaders must weave and manage their webs of promises with great care-encouraging iterative conversation and making sure commitments are fulfilled reliably. If they do, they can enhance coordination and cooperation among colleagues, build the organizational agility required to seize new business opportunities, and tap employees' entrepreneurial energies.

  3. Ensemble of surrogates-based optimization for identifying an optimal surfactant-enhanced aquifer remediation strategy at heterogeneous DNAPL-contaminated sites

    NASA Astrophysics Data System (ADS)

    Jiang, Xue; Lu, Wenxi; Hou, Zeyu; Zhao, Haiqing; Na, Jin

    2015-11-01

    The purpose of this study was to identify an optimal surfactant-enhanced aquifer remediation (SEAR) strategy for aquifers contaminated by dense non-aqueous phase liquid (DNAPL) based on an ensemble of surrogates-based optimization technique. A saturated heterogeneous medium contaminated by nitrobenzene was selected as case study. A new kind of surrogate-based SEAR optimization employing an ensemble surrogate (ES) model together with a genetic algorithm (GA) is presented. Four methods, namely radial basis function artificial neural network (RBFANN), kriging (KRG), support vector regression (SVR), and kernel extreme learning machines (KELM), were used to create four individual surrogate models, which were then compared. The comparison enabled us to select the two most accurate models (KELM and KRG) to establish an ES model of the SEAR simulation model, and the developed ES model as well as these four stand-alone surrogate models was compared. The results showed that the average relative error of the average nitrobenzene removal rates between the ES model and the simulation model for 20 test samples was 0.8%, which is a high approximation accuracy, and which indicates that the ES model provides more accurate predictions than the stand-alone surrogate models. Then, a nonlinear optimization model was formulated for the minimum cost, and the developed ES model was embedded into this optimization model as a constrained condition. Besides, GA was used to solve the optimization model to provide the optimal SEAR strategy. The developed ensemble surrogate-optimization approach was effective in seeking a cost-effective SEAR strategy for heterogeneous DNAPL-contaminated sites. This research is expected to enrich and develop the theoretical and technical implications for the analysis of remediation strategy optimization of DNAPL-contaminated aquifers.

  4. Ensemble of Surrogates-based Optimization for Identifying an Optimal Surfactant-enhanced Aquifer Remediation Strategy at Heterogeneous DNAPL-contaminated Sites

    NASA Astrophysics Data System (ADS)

    Lu, W., Sr.; Xin, X.; Luo, J.; Jiang, X.; Zhang, Y.; Zhao, Y.; Chen, M.; Hou, Z.; Ouyang, Q.

    2015-12-01

    The purpose of this study was to identify an optimal surfactant-enhanced aquifer remediation (SEAR) strategy for aquifers contaminated by dense non-aqueous phase liquid (DNAPL) based on an ensemble of surrogates-based optimization technique. A saturated heterogeneous medium contaminated by nitrobenzene was selected as case study. A new kind of surrogate-based SEAR optimization employing an ensemble surrogate (ES) model together with a genetic algorithm (GA) is presented. Four methods, namely radial basis function artificial neural network (RBFANN), kriging (KRG), support vector regression (SVR), and kernel extreme learning machines (KELM), were used to create four individual surrogate models, which were then compared. The comparison enabled us to select the two most accurate models (KELM and KRG) to establish an ES model of the SEAR simulation model, and the developed ES model as well as these four stand-alone surrogate models was compared. The results showed that the average relative error of the average nitrobenzene removal rates between the ES model and the simulation model for 20 test samples was 0.8%, which is a high approximation accuracy, and which indicates that the ES model provides more accurate predictions than the stand-alone surrogate models. Then, a nonlinear optimization model was formulated for the minimum cost, and the developed ES model was embedded into this optimization model as a constrained condition. Besides, GA was used to solve the optimization model to provide the optimal SEAR strategy. The developed ensemble surrogate-optimization approach was effective in seeking a cost-effective SEAR strategy for heterogeneous DNAPL-contaminated sites. This research is expected to enrich and develop the theoretical and technical implications for the analysis of remediation strategy optimization of DNAPL-contaminated aquifers.

  5. 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

  6. Telepsychiatry: Promise, potential, and challenges

    PubMed Central

    Malhotra, Savita; Chakrabarti, Subho; Shah, Ruchita

    2013-01-01

    Despite the high prevalence and potentially disabling consequences of mental disorders, specialized mental health services are extremely deficient, leading to the so-called ‘Mental Health Gap’. Moreover, the services are concentrated in the urban areas, further worsening the rural-urban and tertiary primary care divide. Strengthening of and expanding the existing human resources and infrastructure, and integrating mental health into primary care appear to be the two major solutions. However, both the strategies are riddled with logistic difficulties and have a long gestation period. In such a scenario, telepsychiatry or e-mental health, defined as the use of information and communication technology to provide or support psychiatric services across distances, appears to be a promising answer. Due to its enormous potential, a review of the existing literature becomes imperative. An extensive search of literature was carried out and has been presented to delineate the modes of communication, acceptability and satisfaction, reliability, outcomes, cost-effectiveness, and legal and ethical challenges related to telepsychiatry. Telepsychiatry has been applied for direct patient care (diagnosis and management), consultation, and training, education, and research purposes. Both real-time, live interaction (synchronous) and store–forward (asynchronous) types of technologies have been used for these purposes. A growing amount of literature shows that training, supervision, and consultation by specialists to primary care physicians through telepsychiatry has several advantages. In this background, we have further focused on the models of telepsychiatry best suited for India, considering that mental health care can be integrated into primary care and taken to the doorstep of patients in the community. PMID:23441027

  7. Molecular Diversity by Olefin Cross-Metathesis on Solid Support. Generation of Libraries of Biologically Promising β-Lactam Derivatives.

    PubMed

    Méndez, Luciana; Poeylaut-Palena, Andrés A; Mata, Ernesto G

    2018-05-16

    The application of the reagent-based diversification strategy for generation of libraries of biologically promising β-lactam derivatives is described. Key features are the versatility of the linker used and the cross-metathesis functionalization at the cleavage step. From an immobilized primary library, diversity was expanded by applying different cleavage conditions, leading to a series of cholesterol absorption inhibitor analogues together with interesting hybrid compounds through incorporation of a chalcone moiety.

  8. 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.

  9. Cost-effectiveness of diagnostic strategies using quantitative real-time PCR and bacterial culture to identify contagious mastitis cases in large dairy herds.

    PubMed

    Murai, Kiyokazu; Lehenbauer, Terry W; Champagne, John D; Glenn, Kathy; Aly, Sharif S

    2014-03-01

    the 3 pathogens. A stochastic model was used to assess the effect of prevalence or herd size on the cost-effectiveness of diagnostic strategies. In the current study, increasing the prevalence of mastitis did not alter the ranking of strategies by cost-effectiveness. However, larger herds could benefit from testing larger pools such as 50 or 100 samples to improve cost-effectiveness. Several diagnostic strategy options exist to identify contagious mastitis in herds, decisions should be based on cost and sensitivity of the strategies available. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Protocol: a systematic review of studies developing and/or evaluating search strategies to identify prognosis studies.

    PubMed

    Corp, Nadia; Jordan, Joanne L; Hayden, Jill A; Irvin, Emma; Parker, Robin; Smith, Andrea; van der Windt, Danielle A

    2017-04-20

    Prognosis research is on the rise, its importance recognised because chronic health conditions and diseases are increasingly common and costly. Prognosis systematic reviews are needed to collate and synthesise these research findings, especially to help inform effective clinical decision-making and healthcare policy. A detailed, comprehensive search strategy is central to any systematic review. However, within prognosis research, this is challenging due to poor reporting and inconsistent use of available indexing terms in electronic databases. Whilst many published search filters exist for finding clinical trials, this is not the case for prognosis studies. This systematic review aims to identify and compare existing methodological filters developed and evaluated to identify prognosis studies of any of the three main types: overall prognosis, prognostic factors, and prognostic [risk prediction] models. Primary studies reporting the development and/or evaluation of methodological search filters to retrieve any type of prognosis study will be included in this systematic review. Multiple electronic bibliographic databases will be searched, grey literature will be sought from relevant organisations and websites, experts will be contacted, and citation tracking of key papers and reference list checking of all included papers will be undertaken. Titles will be screened by one person, and abstracts and full articles will be reviewed for inclusion independently by two reviewers. Data extraction and quality assessment will also be undertaken independently by two reviewers with disagreements resolved by discussion or by a third reviewer if necessary. Filters' characteristics and performance metrics reported in the included studies will be extracted and tabulated. To enable comparisons, filters will be grouped according to database, platform, type of prognosis study, and type of filter for which it was intended. This systematic review will identify all existing validated

  11. 3p22.1p21.31 microdeletion identifies CCK as Asperger syndrome candidate gene and shows the way for therapeutic strategies in chromosome imbalances.

    PubMed

    Iourov, Ivan Y; Vorsanova, Svetlana G; Voinova, Victoria Y; Yurov, Yuri B

    2015-01-01

    In contrast to other autism spectrum disorders, chromosome abnormalities are rare in Asperger syndrome (AS) or high-functioning autism. Consequently, AS was occasionally subjected to classical positional cloning. Here, we report on a case of AS associated with a deletion of the short arm of chromosome 3. Further in silico analysis has identified a candidate gene for AS and has suggested a therapeutic strategy for manifestations of the chromosome rearrangement. Using array comparative genomic hybridization, an interstitial deletion of 3p22.1p21.31 (~2.5 Mb in size) in a child with Asperger's syndrome, seborrheic dermatitis and chronic pancreatitis was detected. Original bioinformatic approach to the prioritization of candidate genes/processes identified CCK (cholecystokinin) as a candidate gene for AS. In addition to processes associated with deleted genes, bioinformatic analysis of CCK gene interactome indicated that zinc deficiency might be a pathogenic mechanism in this case. This suggestion was supported by plasma zinc concentration measurements. The increase of zinc intake produced a rise in zinc plasma concentration and the improvement in the patient's condition. Our study supported previous linkage findings and had suggested a new candidate gene in AS. Moreover, bioinformatic analysis identified the pathogenic mechanism, which was used to propose a therapeutic strategy for manifestations of the deletion. The relative success of this strategy allows speculating that therapeutic or dietary normalization of metabolic processes altered by a chromosome imbalance or genomic copy number variations may be a way for treating at least a small proportion of cases of these presumably incurable genetic conditions.

  12. 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

  13. The promise of a cognitive perspective on jury deliberation.

    PubMed

    Salerno, Jessica M; Diamond, Shari Seidman

    2010-04-01

    Despite much psychological research regarding jury decision making, surprisingly little is known about the deliberation process that gives rise to jury verdicts. We review classic jury decision-making research regarding the importance of deliberation and more recent research, investigating deliberation and hung juries, that challenges the view that deliberation does not have an important impact on verdicts. We advocate greater attention to potential cognitive processes during deliberation that might explain the transition between predeliberation preferences and a jury's ultimate verdict. We then review cognitive work in the group context generally, and the jury context specifically, illustrating the promise of a cognitive perspective on jury deliberation. Finally, we identify cognitive phenomena likely to be particularly valuable in illuminating deliberation behavior.

  14. Young children mostly keep, and expect others to keep, their promises.

    PubMed

    Kanngiesser, Patricia; Köymen, Bahar; Tomasello, Michael

    2017-07-01

    Promises are speech acts that create an obligation to do the promised action. In three studies, we investigated whether 3- and 5-year-olds (N=278) understand the normative implications of promising in prosocial interactions. In Study 1, children helped a partner who promised to share stickers. When the partner failed to uphold the promise, 3- and 5-year-olds protested and referred to promise norms. In Study 2, when children in this same age range were asked to promise to continue a cleaning task-and they agreed-they persisted longer on the task and mentioned their obligation more frequently than without such a promise. They also persisted longer after a promise than after a cleaning reminder (Study 3). In prosocial interactions, thus, young children feel a normative obligation to keep their promises and expect others to keep their promises as well. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Realizing the promises of marine biotechnology.

    PubMed

    Luiten, Esther E M; Akkerman, Ida; Koulman, Albert; Kamermans, Pauline; Reith, Hans; Barbosa, Maria J; Sipkema, Detmer; Wijffels, René H

    2003-07-01

    High-quality research in the field of marine biotechnology is one of the key-factors for successful innovation in exploiting the vast diversity of marine life. However, fascinating scientific research with promising results and claims on promising potential applications (e.g. for pharmaceuticals, nutritional supplements, (feed-)products for aquaculture and bioremediation solutions) is not the only factor to realise the commercial applications of marine biotechnology. What else is needed to exploit the promising potential of marine biotechnology and to create new industrial possibilities? In the study project 'Ocean Farming-Sustainable exploitation of marine organisms', we explore the possibilities of marine organisms to fulfill needs, such as safe and healthy food, industrial (raw) materials and renewable energy in a sustainable way. One of the three design groups is envisioning the future of strong land-based 'marine' market chains. Marine biotechnology is one of the foci of attention in this design group. This article provides a model of future-oriented thinking in which a variety of experts actively participate.

  16. Low alcohol alternatives: a promising strategy for reducing alcohol related harm.

    PubMed

    Segal, David S; Stockwell, Tim

    2009-03-01

    Less than 1% of the beer market in British Columbia comprises beers with an alcohol content below 4%, despite the success of low alcohol beers in other countries, e.g. Australia. A small experimental study is described in which male students were given either unmarked low alcohol beer (3.8%) or regular strength beer (5.3%) to investigate their enjoyment and subjective intoxication. Thirty-four male students who reported drinking 5 or more beers in 1 day at least once in the last month volunteered for the study. In each drinking session, small groups of between 6 and 10 students consumed two servings of beer while playing dominoes. Each subject was his own control in the experiment by attending two group-drinking sessions, drinking a different beverage each time. The different beers were given in balanced order with half the subjects in each group drinking each type of beer. Standard measures of subjective intoxication and enjoyment were used. Blood alcohol levels were tested before, during and after drinking. Although significantly higher blood alcohol levels were obtained with the higher strength beer (means of 0.026 versus 0.033 mg/100 ml at the end of the study, p < 0.001), (i) most participants reported enjoying the two sessions equally or preferred the low alcohol beer session, (ii) most did not report feeling different between the two sessions and (iii) only about half correctly guessed which was the higher alcohol content beer. There was a preference, however, for the taste of the stronger beer. We conclude beer drinkers cannot readily distinguish low and regular strength beers and can enjoy socializing equally with either. We recommend taxation strategies to create incentives for the manufacture, marketing and consumption of low alcohol alternatives.

  17. 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.

  18. Therapeutic RNA interference for neurodegenerative diseases: From promise to progress.

    PubMed

    Gonzalez-Alegre, Pedro

    2007-04-01

    RNA interference (RNAi) has emerged as a powerful tool to manipulate gene expression in the laboratory. Due to its remarkable discriminating properties, individual genes, or even alleles can be targeted with exquisite specificity in cultured cells or living animals. Among its many potential biomedical applications, silencing of disease-linked genes stands out as a promising therapeutic strategy for many incurable disorders. Neurodegenerative diseases represent one of the more attractive targets for the development of therapeutic RNAi. In this group of diseases, the progressive loss of neurons leads to the gradual appearance of disabling neurological symptoms and premature death. Currently available therapies aim to improve the symptoms but not to halt the process of neurodegeneration. The increasing prevalence and economic burden of some of these diseases, such as Alzheimer's disease (AD) or Parkinson's disease (PD), has boosted the efforts invested in the development of interventions, such as RNAi, aimed at altering their natural course. This review will summarize where we stand in the therapeutic application of RNAi for neurodegenerative diseases. The basic principles of RNAi will be reviewed, focusing on features important for its therapeutic manipulation. Subsequently, a stepwise strategy for the development of therapeutic RNAi will be presented. Finally, the different preclinical trials of therapeutic RNAi completed in disease models will be summarized, stressing the experimental questions that need to be addressed before planning application in human disease.

  19. Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug.

    PubMed

    Cardaci, Simone; Desideri, Enrico; Ciriolo, Maria Rosa

    2012-02-01

    The Warburg effect refers to the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions. Although the molecular mechanisms underlying tumor reliance on glycolysis remains not completely clear, its inhibition opens feasible therapeutic windows for cancer treatment. Indeed, several small molecules have emerged by combinatorial studies exhibiting promising anticancer activity both in vitro and in vivo, as a single agent or in combination with other therapeutic modalities. Therefore, besides reviewing the alterations of glycolysis that occur with malignant transformation, this manuscript aims at recapitulating the most effective pharmacological therapeutics of its targeting. In particular, we describe the principal mechanisms of action and the main targets of 3-bromopyruvate, an alkylating agent with impressive antitumor effects in several models of animal tumors. Moreover, we discuss the chemo-potentiating strategies that would make unparalleled the putative therapeutic efficacy of its use in clinical settings.

  20. 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.

  1. 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

  2. Cannabidiol: a promising drug for neurodegenerative disorders?

    PubMed

    Iuvone, Teresa; Esposito, Giuseppe; De Filippis, Daniele; Scuderi, Caterina; Steardo, Luca

    2009-01-01

    Neurodegenerative diseases represent, nowadays, one of the main causes of death in the industrialized country. They are characterized by a loss of neurons in particular regions of the nervous system. It is believed that this nerve cell loss underlies the subsequent decline in cognitive and motor function that patients experience in these diseases. A range of mutant genes and environmental toxins have been implicated in the cause of neurodegenerative disorders but the mechanism remains largely unknown. At present, inflammation, a common denominator among the diverse list of neurodegenerative diseases, has been implicated as a critical mechanism that is responsible for the progressive nature of neurodegeneration. Since, at present, there are few therapies for the wide range of neurodegenerative diseases, scientists are still in search of new therapeutic approaches to the problem. An early contribution of neuroprotective and antiinflammatory strategies for these disorders seems particularly desirable because isolated treatments cannot be effective. In this contest, marijuana derivatives have attracted special interest, although these compounds have always raised several practical and ethical problems for their potential abuse. Nevertheless, among Cannabis compounds, cannabidiol (CBD), which lacks any unwanted psychotropic effect, may represent a very promising agent with the highest prospect for therapeutic use.

  3. Genetic testing for inherited ocular disease: delivering on the promise at last?

    PubMed

    Gillespie, Rachel L; Hall, Georgina; Black, Graeme C

    2014-01-01

    Genetic testing is of increasing clinical utility for diagnosing inherited eye disease. Clarifying a clinical diagnosis is important for accurate estimation of prognosis, facilitating genetic counselling and management of families, and in the future will direct gene-specific therapeutic strategies. Often, precise diagnosis of genetic ophthalmic conditions is complicated by genetic heterogeneity, a difficulty that the so-called 'next-generation sequencing' technologies promise to overcome. Despite considerable counselling and ethical complexities, next-generation sequencing offers to revolutionize clinical practice. This will necessitate considerable adjustment to standard practice but has the power to deliver a personalized approach to genomic medicine for many more patients and enhance the potential for preventing vision loss. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

  4. 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.

  5. The Promise of a College Scholarship Transforms a District

    ERIC Educational Resources Information Center

    Ritter, Gary W.; Ash, Jennifer

    2016-01-01

    Promise programs are place-based scholarships, generally tied to a city or school district, offering near-universal access to all living in the "place." While Promise programs share some characteristics with other scholarship programs, they're unique because they seek to change communities and schools. Underlying such promise programs is…

  6. 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

  7. Identifying Strategies that Facilitate EFL Learners' Oral Communication: A Classroom Study Using Multiple Data Collection Procedures

    ERIC Educational Resources Information Center

    Nakatani, Yasuo

    2010-01-01

    This article considers whether the use of specific communication strategies can improve learners' English proficiency in communicative tasks. Japanese college students (n= 62) participated in a 12-week course of English lessons using a communicative approach with strategy training. To investigate the influence of specific strategy use, their…

  8. 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

  9. Strategy to Identify and Test Putative Light-Sensitive Non-Opsin G-Protein-Coupled Receptors: A Case Study.

    PubMed

    Faggionato, Davide; Serb, Jeanne M

    2017-08-01

    The rise of high-throughput RNA sequencing (RNA-seq) and de novo transcriptome assembly has had a transformative impact on how we identify and study genes in the phototransduction cascade of non-model organisms. But the advantage provided by the nearly automated annotation of RNA-seq transcriptomes may at the same time hinder the possibility for gene discovery and the discovery of new gene functions. For example, standard functional annotation based on domain homology to known protein families can only confirm group membership, not identify the emergence of new biochemical function. In this study, we show the importance of developing a strategy that circumvents the limitations of semiautomated annotation and apply this workflow to photosensitivity as a means to discover non-opsin photoreceptors. We hypothesize that non-opsin G-protein-coupled receptor (GPCR) proteins may have chromophore-binding lysines in locations that differ from opsin. Here, we provide the first case study describing non-opsin light-sensitive GPCRs based on tissue-specific RNA-seq data of the common bay scallop Argopecten irradians (Lamarck, 1819). Using a combination of sequence analysis and three-dimensional protein modeling, we identified two candidate proteins. We tested their photochemical properties and provide evidence showing that these two proteins incorporate 11-cis and/or all-trans retinal and react to light photochemically. Based on this case study, we demonstrate that there is potential for the discovery of new light-sensitive GPCRs, and we have developed a workflow that starts from RNA-seq assemblies to the discovery of new non-opsin, GPCR-based photopigments.

  10. Drug-targeting strategies in cancer therapy.

    PubMed

    Huang, P S; Oliff, A

    2001-02-01

    Genetic changes in cell-cycle, apoptotic, and survival pathways cause tumorigenesis, leading to significant phenotypic changes in transformed cells. These changes in the tumor environment - elevated expression of surface proteases, increased angiogenesis and glucuronidase activity - can be taken advantage of to improve the therapeutic index of existing cancer therapies. Targeting cytotoxics to tumor cells by enzymatic activation is a promising strategy for improving chemotherapeutics.

  11. Discovery of novel drugs for promising targets.

    PubMed

    Martell, Robert E; Brooks, David G; Wang, Yan; Wilcoxen, Keith

    2013-09-01

    Once a promising drug target is identified, the steps to actually discover and optimize a drug are diverse and challenging. The goal of this study was to provide a road map to navigate drug discovery. Review general steps for drug discovery and provide illustrating references. A number of approaches are available to enhance and accelerate target identification and validation. Consideration of a variety of potential mechanisms of action of potential drugs can guide discovery efforts. The hit to lead stage may involve techniques such as high-throughput screening, fragment-based screening, and structure-based design, with informatics playing an ever-increasing role. Biologically relevant screening models are discussed, including cell lines, 3-dimensional culture, and in vivo screening. The process of enabling human studies for an investigational drug is also discussed. Drug discovery is a complex process that has significantly evolved in recent years. © 2013 Elsevier HS Journals, Inc. All rights reserved.

  12. NLEAP/GIS approach for identifying and mitigating regional nitrate-nitrogen leaching

    USGS Publications Warehouse

    Shaffer, M.J.; Hall, M.D.; Wylie, B.K.; Wagner, D.G.; Corwin, D.L.; Loague, K.

    1996-01-01

    Improved simulation-based methodology is needed to help identify broad geographical areas where potential NO3-N leaching may be occurring from agriculture and suggest management alternatives that minimize the problem. The Nitrate Leaching and Economic Analysis Package (NLEAP) model was applied to estimate regional NO3-N leaching in eastern Colorado. Results show that a combined NLEAP/GIS technology can be used to identify potential NO3-N hot spots in shallow alluvial aquifers under irrigated agriculture. The NLEAP NO3-N Leached (NL) index provided the most promising single index followed by NO3-N Available for Leaching (NAL). The same combined technology also shows promise in identifying Best Management Practice (BMP) methods that help minimize NO3-N leaching in vulnerable areas. Future plans call for linkage of the NLEAP/GIS procedures with groundwater modeling to establish a mechanistic analysis of agriculture-aquifer interactions at a regional scale.

  13. Promising Practices for Achieving Patient-centered Hospital Care: A National Study of High-performing US Hospitals.

    PubMed

    Aboumatar, Hanan J; Chang, Bickey H; Al Danaf, Jad; Shaear, Mohammad; Namuyinga, Ruth; Elumalai, Sathyanarayanan; Marsteller, Jill A; Pronovost, Peter J

    2015-09-01

    Patient-centered care is integral to health care quality, yet little is known regarding how to achieve patient-centeredness in the hospital setting. The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey measures patients' reports on clinician behaviors deemed by patients as key to a high-quality hospitalization experience. We conducted a national study of hospitals that achieved the highest performance on HCAHPS to identify promising practices for improving patient-centeredness, common challenges met, and how those were addressed. We identified hospitals that achieved the top ranks or remarkable recent improvements on HCAHPS and surveyed key informants at these hospitals. Using quantitative and qualitative methods, we described the interventions used at these hospitals and developed an explanatory model for achieving patient-centeredness in hospital care. Fifty-two hospitals participated in this study. Hospitals used similar interventions that focused on improving responsiveness to patient needs, the discharge experience, and patient-clinician interactions. To improve responsiveness, hospitals used proactive nursing rounds (reported at 83% of hospitals) and executive/leader rounds (62%); for the discharge experience, multidisciplinary rounds (56%), postdischarge calls (54%), and discharge folders (52%) were utilized; for clinician-patient interactions, hospitals promoted specific desired behaviors (65%) and set behavioral standards (60%) for which employees were held accountable. Similar strategies were also used to achieve successful intervention implementation including HCAHPS data feedback, and employee and leader engagement and accountability. High-performing hospitals used a set of patient-centered care processes that involved both leaders and clinicians in ensuring that patient needs and preferences are addressed.

  14. [Factors influencing research activity of Andalusian nurses and improvement strategies].

    PubMed

    López Alonso, Sergio R; Gálvez González, María; Amezcua, Manuel

    2013-04-01

    To identify factors influencing research activity of Andalusian nurses and to find improvement strategies. Qualitative research using SWOT analysis (weaknesses, threats, strengths, opportunities). Nurses were selected deliberately in eight groups according to predetermined criteria. Analysis included categorization and relationship of factors and strategies. 81 participants were included in groups of 7-12 range. 45 categories were identified with 212 factors: 12 weaknesses (50 factors), 10 strengths (44 factors), 12 threats (68 factors) and 11 opportunities (50 factors). In addition, 32 categories were identified with 53 strategies: 14 categories of W-T strategies (42 strategies), 3 categories of S-T strategies (11 strategies), 5 categories of W-O strategies (13 strategies) and 10 categories of S-O strategies (41 strategies). Nurses identified numerous factors, mainly threats. The strategies are focused on W-T but they also suggest many but weak 5-0 strategies due to the low potential of the opportunities and strengths perceived.

  15. 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.

  16. 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.

  17. Sleep Hygiene and Recovery Strategies in Elite Soccer Players.

    PubMed

    Nédélec, Mathieu; Halson, Shona; Delecroix, Barthélémy; Abaidia, Abd-Elbasset; Ahmaidi, Said; Dupont, Gregory

    2015-11-01

    In elite soccer, players are frequently exposed to various situations and conditions that can interfere with sleep (e.g., playing night matches interspersed with 3 days; performing activities demanding high levels of concentration close to bedtime; use of products containing caffeine or alcohol in the period preceding bedtime; regular daytime napping throughout the week; variable wake-up times or bedtime), potentially leading to sleep deprivation. We outline simple, practical, and pharmaceutical-free sleep strategies that are coordinated to the constraints of elite soccer in order to promote sleep. Sleep deprivation is best alleviated by sleep extension; however, sleep hygiene strategies (i.e., consistent sleep pattern, appropriate napping, and active daytime behaviors) can be utilized to promote restorative sleep. Light has a profound impact on sleep, and sleep hygiene strategies that support the natural environmental light-dark cycle (i.e., red-light treatment prior to sleep, dawn-simulation therapy prior to waking) and prevent cycle disruption (i.e., filtering short wavelengths prior to sleep) may be beneficial to elite soccer players. Under conditions of inordinate stress, techniques such as brainwave entrainment and meditation are promising sleep-promoting strategies, but future studies are required to ascertain the applicability of these techniques to elite soccer players. Consuming high-electrolyte fluids such as milk, high-glycemic index carbohydrates, some forms of protein immediately prior to sleep, as well as tart cherry juice concentrate and tryptophan may promote rehydration, substrate stores replenishment, muscle-damage repair and/or restorative sleep. The influence of cold water immersion performed close to bedtime on subsequent sleep is still debated. Conversely, the potential detrimental effects of sleeping medication must be recognized. Sleep initiation is influenced by numerous factors, reinforcing the need for future research to identify such

  18. Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity.

    PubMed

    Davis, Elizabeth; Sloan, Tyler; Aurelius, Krista; Barbour, Angela; Bodey, Elijah; Clark, Brigette; Dennis, Celeste; Drown, Rachel; Fleming, Megan; Humbert, Allison; Glasgo, Elizabeth; Kerns, Trent; Lingro, Kelly; McMillin, MacKenzie; Meyer, Aaron; Pope, Breanna; Stalevicz, April; Steffen, Brittney; Steindl, Austin; Williams, Carolyn; Wimberley, Carmen; Zenas, Robert; Butela, Kristen; Wildschutte, Hans

    2017-06-01

    The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil-derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole-genome sequencing and linker-mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  19. Gold Nanoparticles: Promising Agent to Improve the Diagnosis and Therapy of Cancer.

    PubMed

    Ning, Limin; Zhu, Benwei; Gao, Tao

    2017-01-01

    Gold nanoparticles have been exploited for nanobiotechnology applications for the last two decades. New insights of the nanomaterials as promising agent for cancer diagnosis and therapy have just started to emerge. Due to the size- and shape-dependent optical, electrical and thermal properties, gold nanoparticles are being developed as diagnostic reagents, drug carriers, contrast agents, photothermal agents and radiosensitisers. This review aims to summarize the latest advances of gold nanoparticles in cancer treatment. We undertook a systematical search for research literatures using a well-framed review question and presented the applications in different fields, including early cancer diagnosis, imaging, radiotherapy, chemotherapy, gene therapy and photothermal therapy, which were fully described, filtered, combined and analyzed in order to provide documented proofs on the applications of gold nanoparticles in current cancer treatments. One hundred and sixty papers were included in the review, the majority of which represent latest researches in the field of gold nanoparticle-based diagnosis and therapy for cancer. Conventional treatment strategies for cancer cannot identify normal and cancer cells. While due to the high surface area to volume ratio and rich surface functionalization chemistry, gold nanoparticle can greatly enhance the targeting with adverse side effects of traditional treatment on normal tissues being avoided. Gold nanoparticles have greatly improved the traditional treatment due to their unique properties. However, their size-dependent toxicity, distribution and clearance need further studies to make them a clinical reality. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. [Aedes aegypti control strategies: a review].

    PubMed

    Zara, Ana Laura de Sene Amâncio; Santos, Sandra Maria Dos; Fernandes-Oliveira, Ellen Synthia; Carvalho, Roberta Gomes; Coelho, Giovanini Evelim

    2016-01-01

    to describe the main strategies to control Aedes aegypti, with emphasis on promising technological innovations for use in Brazil. this study is a non-systematic review of the literature. several technologies have been developed as alternatives in the control of Ae. aegypti, using different mechanisms of action, such as selective monitoring of the infestation, social interventions, dispersing insecticides, new biological control agents and molecular techniques for population control of mosquitoes, also considering the combination between them. Evolving technologies require evaluation of the effectiveness, feasibility and costs of implementation strategies as complementary to the actions already recommended by the National Program for Dengue Control. the integration of different compatible and effective vector control strategies, considering the available technologies and regional characteristics, appears to be a viable method to try to reduce the infestation of mosquitoes and the incidence of arbovirus transmitted by them.

  1. Annual Research Review: Discovery science strategies in studies of the pathophysiology of child and adolescent psychiatric disorders--promises and limitations.

    PubMed

    Zhao, Yihong; Castellanos, F Xavier

    2016-03-01

    Psychiatric science remains descriptive, with a categorical nosology intended to enhance interobserver reliability. Increased awareness of the mismatch between categorical classifications and the complexity of biological systems drives the search for novel frameworks including discovery science in Big Data. In this review, we provide an overview of incipient approaches, primarily focused on classically categorical diagnoses such as schizophrenia (SZ), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD), but also reference convincing, if focal, advances in cancer biology, to describe the challenges of Big Data and discovery science, and outline approaches being formulated to overcome existing obstacles. A paradigm shift from categorical diagnoses to a domain/structure-based nosology and from linear causal chains to complex causal network models of brain-behavior relationship is ongoing. This (r)evolution involves appreciating the complexity, dimensionality, and heterogeneity of neuropsychiatric data collected from multiple sources ('broad' data) along with data obtained at multiple levels of analysis, ranging from genes to molecules, cells, circuits, and behaviors ('deep' data). Both of these types of Big Data landscapes require the use and development of robust and powerful informatics and statistical approaches. Thus, we describe Big Data analysis pipelines and the promise and potential limitations in using Big Data approaches to study psychiatric disorders. We highlight key resources available for psychopathological studies and call for the application and development of Big Data approaches to dissect the causes and mechanisms of neuropsychiatric disorders and identify corresponding biomarkers for early diagnosis. © 2016 Association for Child and Adolescent Mental Health.

  2. Annual Research Review: Discovery science strategies in studies of the pathophysiology of child and adolescent psychiatric disorders: promises and limitations

    PubMed Central

    Zhao, Yihong; Castellanos, F. Xavier

    2015-01-01

    Background and Scope Psychiatric science remains descriptive, with a categorical nosology intended to enhance inter-observer reliability. Increased awareness of the mismatch between categorical classifications and the complexity of biological systems drives the search for novel frameworks including discovery science in Big Data. In this review, we provide an overview of incipient approaches, primarily focused on classically categorical diagnoses such as schizophrenia (SZ), autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), but also reference convincing, if focal, advances in cancer biology, to describe the challenges of Big Data and discovery science, and outline approaches being formulated to overcome existing obstacles. Findings A paradigm shift from categorical diagnoses to a domain/structure-based nosology and from linear causal chains to complex causal network models of brain-behavior relationship is ongoing. This (r)evolution involves appreciating the complexity, dimensionality and heterogeneity of neuropsychiatric data collected from multiple sources (“broad” data) along with data obtained at multiple levels of analysis, ranging from genes to molecules, cells, circuits and behaviors (“deep” data). Both of these types of Big Data landscapes require the use and development of robust and powerful informatics and statistical approaches. Thus, we describe Big Data analysis pipelines and the promise and potential limitations in using Big Data approaches to study psychiatric disorders. Conclusion We highlight key resources available for psychopathological studies and call for the application and development of Big Data approaches to dissect the causes and mechanisms of neuropsychiatric disorders and identify corresponding biomarkers for early diagnosis. PMID:26732133

  3. A strategy to identify linker-based modules for the allosteric regulation of antibody-antigen binding affinities of different scFvs

    PubMed Central

    Thie, Holger

    2017-01-01

    ABSTRACT Antibody single-chain variable fragments (scFvs) are used in a variety of applications, such as for research, diagnosis and therapy. Essential for these applications is the extraordinary specificity, selectivity and affinity of antibody paratopes, which can also be used for efficient protein purification. However, this use is hampered by the high affinity for the protein to be purified because harsh elution conditions, which may impair folding, integrity or viability of the eluted biomaterials, are typically required. In this study, we developed a strategy to obtain structural elements that provide allosteric modulation of the affinities of different antibody scFvs for their antigen. To identify suitable allosteric modules, a complete set of cyclic permutations of calmodulin variants was generated and tested for modulation of the affinity when substituting the linker between VH and VL. Modulation of affinity induced by addition of different calmodulin-binding peptides at physiologic conditions was demonstrated for 5 of 6 tested scFvs of different specificities and antigens ranging from cell surface proteins to haptens. In addition, a variety of different modulator peptides were tested. Different structural solutions were found in respect of the optimal calmodulin permutation, the optimal peptide and the allosteric effect for scFvs binding to different antigen structures. Significantly, effective linker modules were identified for scFvs with both VH-VL and VL-VH architecture. The results suggest that this approach may offer a rapid, paratope-independent strategy to provide allosteric regulation of affinity for many other antibody scFvs. PMID:28055297

  4. Strategies for identifying new prions in yeast

    PubMed Central

    MacLea, Kyle S

    2011-01-01

    The unexpected discovery of two prions, [URE3] and [PSI+], in Saccharomyces cerevisiae led to questions about how many other proteins could undergo similar prion-based structural conversions. However, [URE3] and [PSI+] were discovered by serendipity in genetic screens. Cataloging the full range of prions in yeast or in other organisms will therefore require more systematic search methods. Taking advantage of some of the unique features of prions, various researchers have developed bioinformatic and experimental methods for identifying novel prion proteins. These methods have generated long lists of prion candidates. The systematic testing of some of these prion candidates has led to notable successes; however, even in yeast, where rapid growth rate and ease of genetic manipulation aid in testing for prion activity, such candidate testing is laborious. Development of better methods to winnow the field of prion candidates will greatly aid in the discovery of new prions, both in yeast and in other organisms, and help us to better understand the role of prions in biology. PMID:22052351

  5. 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.

  6. [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.

  7. Nanotechnology: Its Promise and Challenges

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

    Colvin, Vicki

    2009-05-14

    Vicki Colvin of Rice University talks about how nanotechnology-enabled systems, with dimensions on the scale of a billionth of a meter, offer great promise for solving difficult social problems and creating enormous possibilities.

  8. Medulloblastoma stem cells: Promising targets in medulloblastoma therapy.

    PubMed

    Huang, Guo-Hao; Xu, Qing-Fu; Cui, You-Hong; Li, Ningning; Bian, Xiu-Wu; Lv, Sheng-Qing

    2016-05-01

    Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite great improvements in the therapeutic regimen, relapse and leptomeningeal dissemination still pose great challenges to the long-term survival of MB patients. Developing more effective strategies has become extremely urgent. In recent years, a number of malignancies, including MB, have been found to contain a subpopulation of cancer cells known as cancer stem cells (CSCs), or tumor initiating/propagating cells. The CSCs are thought to be largely responsible for tumor initiation, maintenance, dissemination, and relapse; therefore, their pivotal roles have revealed them to be promising targets in MB therapy. Our growing understanding of the major medulloblastoma molecular subgroups and the derivation of some of these groups from specific stem or progenitor cells adds additional layers to the CSC knowledge base. Herein we review the current knowledge of MB stem cells, highlight the molecular mechanisms relating to MB relapse and leptomeningeal dissemination, and incorporate these with the need to develop more effective and accurate therapies for MB patients. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  9. 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

  10. 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…

  11. Cancer Chemoprevention by Dietary Polyphenols: Promising Role for Epigenetics

    PubMed Central

    Link, Alexander; Balaguer, Francesc; Goel, Ajay

    2010-01-01

    Epigenetics refers to heritable changes that are not encoded in the DNA sequence itself, but play an important role in the control of gene expression. In mammals, epigenetic mechanisms include changes in DNA methylation, histone modifications and non-coding RNAs. Although epigenetic changes are heritable in somatic cells, these modifications are also potentially reversible, which makes them attractive and promising avenues for tailoring cancer preventive and therapeutic strategies. Burgeoning evidence in the last decade has provided unprecedented clues that diet and environmental factors directly influence epigenetic mechanisms in humans. Dietary polyphenols from green tea, turmeric, soybeans, broccoli and others have shown to possess multiple cell-regulatory activities within cancer cells. More recently, we have begun to understand that some of the dietary polyphenols may exert their chemopreventive effects in part by modulating various components of the epigenetic machinery in humans. In this article, we first discuss the contribution of diet and environmental factors on epigenetic alterations; subsequently, we provide a comprehensive review of literature on the role of various dietary polyphenols. In particular, we summarize the current knowledge on a large number of dietary agents and their effects on DNA methylation, histone modifications and regulation of expression of non-coding miRNAs in various in vitro and in vivo models. We emphasize how increased understanding of the chemopreventive effects of dietary polyphenols on specific epigenetic alterations may provide unique and yet unexplored novel and highly effective chemopreventive strategies for reducing the health burden of cancer and other diseases in humans. PMID:20599773

  12. 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

  13. 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

  14. Cell-Based Strategies for Meniscus Tissue Engineering

    PubMed Central

    Niu, Wei; Guo, Weimin; Han, Shufeng; Zhu, Yun; Liu, Shuyun; Guo, Quanyi

    2016-01-01

    Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering. PMID:27274735

  15. Strategies for public health research in European Union countries.

    PubMed

    Grimaud, Olivier; McCarthy, Mark; Conceição, Claudia

    2013-11-01

    'Health' is an identifiable theme within the European Union multi-annual research programmes. Public Health Innovation and Research in Europe (PHIRE), led by the European Public Health Association, sought to identify public health research strategies in EU member states. Within PHIRE, national public health associations reviewed structures for health research, held stakeholder workshops and produced reports. This information, supplemented by further web searches, including using assisted translation, was analysed for national research strategies and health research strategies. All countries described general research strategies, outlining organizational and capacity objectives. Thematic fields, including health, are mentioned in some strategies. A health research strategy was identified for 15 EU countries and not for 12. Ministries of health led research strategies for nine countries. Public health research was identified in only three strategies. National research strategies did not refer to the European Union's health research programme. Public health research strategies of European countries need to be developed by ministries of health, working with the research community to achieve the European Research Area.

  16. Engaging Women in Computer Science and Engineering: Promising Practices for Promoting Gender Equity in Undergraduate Research Experiences

    ERIC Educational Resources Information Center

    Kim, Karen A.; Fann, Amy J.; Misa-Escalante, Kimberly O.

    2011-01-01

    Building on research that identifies and addresses issues of women's underrepresentation in computing, this article describes promising practices in undergraduate research experiences that promote women's long-term interest in computer science and engineering. Specifically, this article explores whether and how REU programs include programmatic…

  17. When a desired home death does not occur: the consequences of broken promises.

    PubMed

    Topf, Lorrianne; Robinson, Carole A; Bottorff, Joan L

    2013-08-01

    Evidence shows that most people prefer to die at home; however, the majority of expected deaths occur away from home. Although home deaths require family caregiver (FCG) commitment and care, we understand very little about their experiences in this context. The study's aim was to gain a better understanding of the experiences of FCGs when circumstances prevented a desired home death for a family member with advanced cancer. An interpretive description approach was used. Data collection involved semistructured interviews. Field notes and reflective journaling aided interpretive and analytical processes. The study was conducted in western Canada and included 18 bereaved FCGs. FCGs were committed to the promises made to care for their family member at home until death. These promises were challenged by a lack of preparedness for caregiving, difficulty accessing professional support and information, and frustration with the inadequate help they received. The events that precipitated dying family members leaving their home for hospital or hospice were unexpected and often influenced by FCGs' lack of situation-specific knowledge and ability to cope with complex caregiving responsibilities. FCGs found it extremely challenging to reconcile with breaking their promise to care at home until death and many were unable to do so. FCGs' despair about not being able to keep their promise for a home death was related to complicated bereavement. Prospective studies of the experiences of FCGs who are aiming for home deaths are needed to identify both short- and long-term interventions to effectively support death at home.

  18. Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma.

    PubMed

    Favoni, Roberto E; Daga, Antonio; Malatesta, Paolo; Florio, Tullio

    2012-05-01

    The incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up-to-date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum derivatives and pemetrexed or raltitrexed, as preferred first-line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy-resistant disease. Over these foundations, several promising studies are ongoing at preclinical level and novel molecules are currently under evaluation as well. Yet, established tumour cell lines, used for decades to investigate the efficacy of anticancer agents, although still the main source of drug efficacy studies, after long-term cultures tend to biologically diverge from the original tumour, limiting the predictive potential of in vivo efficacy. Cancer stem cells (CSCs), a subpopulation of malignant cells capable of self-renewal and multilineage differentiation, are believed to play an essential role in cancer initiation, growth, metastasization and relapse, being responsible of chemo- and radiotherapy refractoriness. According to the current carcinogenesis theory, CSCs represent the tumour-initiating cell (TIC) fraction, the only clonogenic subpopulation able to originate a tumour mass. Consequently, the recently described isolation of TICs from hMPM, the proposed main pharmacological target for novel antitumoural drugs, may contribute to better dissect the biology and multidrug resistance pathways controlling hMPM growth. © 2012 The Authors. British Journal of Pharmacology © 2012 The

  19. Neuroimaging in psychiatric pharmacogenetics research: the promise and pitfalls.

    PubMed

    Falcone, Mary; Smith, Ryan M; Chenoweth, Meghan J; Bhattacharjee, Abesh Kumar; Kelsoe, John R; Tyndale, Rachel F; Lerman, Caryn

    2013-11-01

    The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype × drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment.

  20. Beyond "implementation strategies": classifying the full range of strategies used in implementation science and practice.

    PubMed

    Leeman, Jennifer; Birken, Sarah A; Powell, Byron J; Rohweder, Catherine; Shea, Christopher M

    2017-11-03

    Strategies are central to the National Institutes of Health's definition of implementation research as "the study of strategies to integrate evidence-based interventions into specific settings." Multiple scholars have proposed lists of the strategies used in implementation research and practice, which they increasingly are classifying under the single term "implementation strategies." We contend that classifying all strategies under a single term leads to confusion, impedes synthesis across studies, and limits advancement of the full range of strategies of importance to implementation. To address this concern, we offer a system for classifying implementation strategies that builds on Proctor and colleagues' (2013) reporting guidelines, which recommend that authors not only name and define their implementation strategies but also specify who enacted the strategy (i.e., the actor) and the level and determinants that were targeted (i.e., the action targets). We build on Wandersman and colleagues' Interactive Systems Framework to distinguish strategies based on whether they are enacted by actors functioning as part of a Delivery, Support, or Synthesis and Translation System. We build on Damschroder and colleague's Consolidated Framework for Implementation Research to distinguish the levels that strategies target (intervention, inner setting, outer setting, individual, and process). We then draw on numerous resources to identify determinants, which are conceptualized as modifiable factors that prevent or enable the adoption and implementation of evidence-based interventions. Identifying actors and targets resulted in five conceptually distinct classes of implementation strategies: dissemination, implementation process, integration, capacity-building, and scale-up. In our descriptions of each class, we identify the level of the Interactive System Framework at which the strategy is enacted (actors), level and determinants targeted (action targets), and outcomes used to

  1. 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.

  2. 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.

  3. High-throughput matrix screening identifies synergistic and antagonistic antimalarial drug combinations

    PubMed Central

    Mott, Bryan T.; Eastman, Richard T.; Guha, Rajarshi; Sherlach, Katy S.; Siriwardana, Amila; Shinn, Paul; McKnight, Crystal; Michael, Sam; Lacerda-Queiroz, Norinne; Patel, Paresma R.; Khine, Pwint; Sun, Hongmao; Kasbekar, Monica; Aghdam, Nima; Fontaine, Shaun D.; Liu, Dongbo; Mierzwa, Tim; Mathews-Griner, Lesley A.; Ferrer, Marc; Renslo, Adam R.; Inglese, James; Yuan, Jing; Roepe, Paul D.; Su, Xin-zhuan; Thomas, Craig J.

    2015-01-01

    Drug resistance in Plasmodium parasites is a constant threat. Novel therapeutics, especially new drug combinations, must be identified at a faster rate. In response to the urgent need for new antimalarial drug combinations we screened a large collection of approved and investigational drugs, tested 13,910 drug pairs, and identified many promising antimalarial drug combinations. The activity of known antimalarial drug regimens was confirmed and a myriad of new classes of positively interacting drug pairings were discovered. Network and clustering analyses reinforced established mechanistic relationships for known drug combinations and identified several novel mechanistic hypotheses. From eleven screens comprising >4,600 combinations per parasite strain (including duplicates) we further investigated interactions between approved antimalarials, calcium homeostasis modulators, and inhibitors of phosphatidylinositide 3-kinases (PI3K) and the mammalian target of rapamycin (mTOR). These studies highlight important targets and pathways and provide promising leads for clinically actionable antimalarial therapy. PMID:26403635

  4. 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

  5. Evaluation of testing strategies to identify infected animals at a single round of testing within dairy herds known to be infected with Mycobacterium avium ssp. paratuberculosis.

    PubMed

    More, S J; Cameron, A R; Strain, S; Cashman, W; Ezanno, P; Kenny, K; Fourichon, C; Graham, D

    2015-08-01

    As part of a broader control strategy within herds known to be infected with Mycobacterium avium ssp. paratuberculosis (MAP), individual animal testing is generally conducted to identify infected animals for action, usually culling. Opportunities are now available to quantitatively compare different testing strategies (combinations of tests) in known infected herds. This study evaluates the effectiveness, cost, and cost-effectiveness of different testing strategies to identify infected animals at a single round of testing within dairy herds known to be MAP infected. A model was developed, taking account of both within-herd infection dynamics and test performance, to simulate the use of different tests at a single round of testing in a known infected herd. Model inputs included the number of animals at different stages of infection, the sensitivity and specificity of each test, and the costs of testing and culling. Testing strategies included either milk or serum ELISA alone or with fecal culture in series. Model outputs included effectiveness (detection fraction, the proportion of truly infected animals in the herd that are successfully detected by the testing strategy), cost, and cost-effectiveness (testing cost per true positive detected, total cost per true positive detected). Several assumptions were made: MAP was introduced with a single animal and no management interventions were implemented to limit within-herd transmission of MAP before this test. In medium herds, between 7 and 26% of infected animals are detected at a single round of testing, the former using the milk ELISA and fecal culture in series 5 yr after MAP introduction and the latter using fecal culture alone 15 yr after MAP introduction. The combined costs of testing and culling at a single round of testing increases with time since introduction of MAP infection, with culling costs being much greater than testing costs. The cost-effectiveness of testing varied by testing strategy. It was also

  6. 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.

  7. Establishing an ISO 10001-based promise in inpatients care.

    PubMed

    Khan, Mohammad Ashiqur Rahman; Karapetrovic, Stanislav

    2015-01-01

    The purpose of this paper is to explore ISO 10001:2007 in planning, designing and developing a customer satisfaction promise (CSP) intended for inpatients care. Through meetings and interviews with research participants, who included a program manager, unit managers and registered nurses, information about potential promises and their implementation was obtained and analyzed. A number of promises were drafted and one was finally selected to be developed as a CSP. Applying the standard required adaptation and novel interpretation. Additionally, ISO 10002:2004 (Clause 7) was used to design the feedback handling activities. A promise initially chosen for development turned out to be difficult to implement, experience that helped in selecting and developing the final promise. Research participants found the ISO 10001-based method useful and comprehensible. This paper presents a specific health care example of how to adapt a standard's guideline in establishing customer promises. The authors show how a promise can be used in alleviating an existing issue (i.e. communication between carers and patients). The learning can be beneficial in various health care settings. To the knowledge, this paper shows the first example of applying ISO 10001:2007 in a health care case. A few activities suggested by the standard are further detailed, and a new activity is introduced. The integrated use of ISO 10001:2007 and 10002:2004 is presented and how one can be "augmented" by the other is demonstrated.

  8. 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…

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Tetraspanin CD9 and ectonucleotidase CD73 identify an osteochondroprogenitor population with elevated osteogenic properties.

    PubMed

    Singh, Anju; Lester, Chantel; Drapp, Rebecca; Hu, Dorothy Z; Glimcher, Laurie H; Jones, Dallas

    2015-02-01

    Cell-based bone regeneration strategies offer promise for traumatic bone injuries, congenital defects, non-union fractures and other skeletal pathologies. Postnatal bone remodeling and fracture healing provide evidence that an osteochondroprogenitor cell is present in adult life that can differentiate to remodel or repair the fractured bone. However, cell-based skeletal repair in the clinic is still in its infancy, mostly due to poor characterization of progenitor cells and lack of knowledge about their in vivo behavior. Here, we took a combined approach of high-throughput screening, flow-based cell sorting and in vivo transplantation to isolate markers that identify osteochondroprogenitor cells. We show that the presence of tetraspanin CD9 enriches for osteochondroprogenitors within CD105(+) mesenchymal cells and that these cells readily form bone upon transplantation. In addition, we have used Thy1.2 and the ectonucleotidase CD73 to identify subsets within the CD9(+) population that lead to endochondral or intramembranous-like bone formation. Utilization of this unique cell surface phenotype to enrich for osteochondroprogenitor cells will allow for further characterization of the molecular mechanisms that regulate their osteogenic properties. © 2015. Published by The Company of Biologists Ltd.

  14. Promise Neighborhoods: The Promise and Politics of Community Capacity Building as Urban School Reform

    ERIC Educational Resources Information Center

    Horsford, Sonya Douglass; Sampson, Carrie

    2014-01-01

    The purpose of this inquiry is to consider how the U.S. Department of Education's Promise Neighborhoods (PNs) program can improve persistently low-achieving urban schools by making their "neighborhoods whole again" through community capacity building for education reform. As the "first federal initiative to put education at the…

  15. 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.

  16. A physarum-inspired prize-collecting steiner tree approach to identify subnetworks for drug repositioning.

    PubMed

    Sun, Yahui; Hameed, Pathima Nusrath; Verspoor, Karin; Halgamuge, Saman

    2016-12-05

    Drug repositioning can reduce the time, costs and risks of drug development by identifying new therapeutic effects for known drugs. It is challenging to reposition drugs as pharmacological data is large and complex. Subnetwork identification has already been used to simplify the visualization and interpretation of biological data, but it has not been applied to drug repositioning so far. In this paper, we fill this gap by proposing a new Physarum-inspired Prize-Collecting Steiner Tree algorithm to identify subnetworks for drug repositioning. Drug Similarity Networks (DSN) are generated using the chemical, therapeutic, protein, and phenotype features of drugs. In DSNs, vertex prizes and edge costs represent the similarities and dissimilarities between drugs respectively, and terminals represent drugs in the cardiovascular class, as defined in the Anatomical Therapeutic Chemical classification system. A new Physarum-inspired Prize-Collecting Steiner Tree algorithm is proposed in this paper to identify subnetworks. We apply both the proposed algorithm and the widely-used GW algorithm to identify subnetworks in our 18 generated DSNs. In these DSNs, our proposed algorithm identifies subnetworks with an average Rand Index of 81.1%, while the GW algorithm can only identify subnetworks with an average Rand Index of 64.1%. We select 9 subnetworks with high Rand Index to find drug repositioning opportunities. 10 frequently occurring drugs in these subnetworks are identified as candidates to be repositioned for cardiovascular diseases. We find evidence to support previous discoveries that nitroglycerin, theophylline and acarbose may be able to be repositioned for cardiovascular diseases. Moreover, we identify seven previously unknown drug candidates that also may interact with the biological cardiovascular system. These discoveries show our proposed Prize-Collecting Steiner Tree approach as a promising strategy for drug repositioning.

  17. Hemodialysis: stressors and coping strategies.

    PubMed

    Ahmad, Muayyad M; Al Nazly, Eman K

    2015-01-01

    End-stage renal disease (ESRD) is an irreversible and life-threatening condition. In Jordan, the number of ESRD patients treated with hemodialysis is on the rise. Identifying stressors and coping strategies used by patients with ESRD may help nurses and health care providers to gain a clearer understanding of the condition of these patients and thus institute effective care planning. The purpose of this study was to identify stressors perceived by Jordanian patients on hemodialysis, and the coping strategies used by them. A convenience sample of 131 Jordanian men and women was recruited from outpatients' dialysis units in four hospitals. Stressors perceived by participants on hemodialysis and the coping strategies were measured using Hemodialysis Stressor Scale, and Ways of Coping Scale-Revised. Findings showed that patients on hemodialysis psychosocial stressors scores mean was higher than the physiological stressors mean. Positive reappraisal coping strategy had the highest mean among the coping strategies and the lowest mean was accepting responsibility. Attention should be focused towards the psychosocial stressors of patients on hemodialysis and also helping patients utilize the coping strategies that help to alleviate the stressors. The most used coping strategy was positive reappraisal strategy which includes faith and prayer.

  18. 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

  19. Research on Self-Management Techniques Used by Students with Disabilities in General Education Settings: A Promise Fulfilled?

    ERIC Educational Resources Information Center

    McDougall, Dennis; Skouge, Jim; Farrell, Anthony; Hoff, Kathy

    2006-01-01

    This comprehensive review synthesizes findings from 43 studies in which students with disabilities utilized behavioral self-management (BSM) techniques in general education settings. Findings suggest that the long-standing promise of BSM as an inclusive technique has been partially fulfilled. The review identifies strengths and limitations of BSM…

  20. 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.

  1. Strategies to alter the natural history of childhood asthma

    PubMed Central

    Lee-Sarwar, K; Bacharier, L; Litonjua, A

    2017-01-01

    Purpose of review Asthma exhibits significant heterogeneity in occurrence and severity over the lifespan. Our goal is to discuss recent evidence regarding determinants of the natural history of asthma during childhood, and review the rationale behind and status of major efforts to alter its course. Recent findings Variations in microbial exposures are associated with risk of allergic disease, and the use of bacterial lysates may be a promising preventive strategy. Exposure to air pollution appears to be particularly damaging in prenatal and early life, and interventions to reduce pollution are feasible and result in clinical benefit. E-cigarette use may have a role in harm reduction for conventional cigarette smokers with asthma, but has undefined short- and long-term effects that must be clarified. Vitamin D insufficiency over the first several years of life is associated with risk of asthma, and vitamin D supplementation reduces the risk of severe exacerbations. Summary The identification of risk factors for asthma occurrence, persistence and severity will continue to guide efforts to alter the natural history of the disease. We have reviewed several promising strategies that are currently under investigation. Vitamin D supplementation and air pollution reduction have been shown to be effective strategies and warrant increased investigation and implementation. PMID:28079559

  2. 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

  3. BMI-1, a promising therapeutic target for human cancer

    PubMed Central

    WANG, MIN-CONG; LI, CHUN-LI; CUI, JIE; JIAO, MIN; WU, TAO; JING, LI; NAN, KE-JUN

    2015-01-01

    BMI-1 oncogene is a member of the polycomb-group gene family and a transcriptional repressor. Overexpression of BMI-1 has been identified in various human cancer tissues and is known to be involved in cancer cell proliferation, cell invasion, distant metastasis, chemosensitivity and patient survival. Accumulating evidence has revealed that BMI-1 is also involved in the regulation of self-renewal, differentiation and tumor initiation of cancer stem cells (CSCs). However, the molecular mechanisms underlying these biological processes remain unclear. The present review summarized the function of BMI-1 in different human cancer types and CSCs, and discussed the signaling pathways in which BMI-1 is potentially involved. In conclusion, BMI-1 may represent a promising target for the prevention and therapy of various cancer types. PMID:26622537

  4. The Promise of Neuroprotective Agents in Parkinson’s Disease

    PubMed Central

    Seidl, Stacey E.; Potashkin, Judith A.

    2011-01-01

    Parkinson’s disease (PD) is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction, and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline, and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available. PMID:22125548

  5. Understanding retirement: the promise of life-span developmental frameworks.

    PubMed

    Löckenhoff, Corinna E

    2012-09-01

    The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.

  6. The promise of advanced technology for future air transports

    NASA Technical Reports Server (NTRS)

    Bower, R. E.

    1978-01-01

    Progress in all weather 4-D navigation and wake vortex attenuation research is discussed and the concept of time based metering of aircraft is recommended for increased emphasis. The far term advances in aircraft efficiency were shown to be skin friction reduction and advanced configuration types. The promise of very large aircraft, possibly all wing aircraft is discussed, as is an advanced concept for an aerial relay transportation system. Very significant technological developments were identified that can improve supersonic transport performance and reduce noise. The hypersonic transport was proposed as the ultimate step in air transportation in the atmosphere. Progress in the key technology areas of propulsion and structures was reviewed. Finally, the impact of alternate fuels on future air transports was considered and shown not to be a growth constraint.

  7. 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

  8. 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.

  9. Our Children...Today's Investment, Tomorrow's Promise. Building an Early Childhood Development System for Nova Scotia.

    ERIC Educational Resources Information Center

    2001

    This report provides the framework for response to Nova Scotia's agreement with the government of Canada to invest in an early childhood development (ECD) strategy. The report begins with a list of guiding principles for child and family services. The major challenge for the ECD strategy is to identify the key areas of investment that will create…

  10. Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series.

    PubMed

    Kommoss, S; McConechy, M K; Kommoss, F; Leung, S; Bunz, A; Magrill, J; Britton, H; Kommoss, F; Grevenkamp, F; Karnezis, A; Yang, W; Lum, A; Krämer, B; Taran, F; Staebler, A; Lax, S; Brucker, S Y; Huntsman, D G; Gilks, C B; McAlpine, J N; Talhouk, A

    2018-05-01

    We have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB [89 (19.7%)], stage II [26 (5.8%)], and stage III/IV [61 (13.5%)]. ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P = 0.001) and disease-specific (P = 0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, κ 0.88. We have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy

  11. 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...

  12. Presidential Promises.

    ERIC Educational Resources Information Center

    Kennedy, Mike

    2000-01-01

    Explores the different strategies between George W. Bush and Al Gore for improving education. The pros and cons of school vouchers are highlighted along with issues of school safety, tax credits, teacher hiring increases, charter schools, and universal access to education. Republican and Democratic proposals on school safety conclude the article.…

  13. 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.

  14. Mining Social Entrepreneurship Strategies Using Topic Modeling.

    PubMed

    Chandra, Yanto; Jiang, Li Crystal; Wang, Cheng-Jun

    2016-01-01

    Despite the burgeoning research on social entrepreneurship (SE), SE strategies remain poorly understood. Drawing on extant research on the social activism and social change, empowerment and SE models, we explore, classify and validate the strategies used by 2,334 social entrepreneurs affiliated with the world's largest SE support organization, Ashoka. The results of the topic modeling of the social entrepreneurs' strategy profiles reveal that they employed a total of 39 change-making strategies that vary across resources (material versus symbolic strategies), specificity (general versus specific strategies), and mode of participation (mass versus elite participation strategies); they also vary across fields of practice and time. Finally, we identify six meta-SE strategies-a reduction from the 39 strategies-and identify four new meta-SE strategies (i.e., system reform, physical capital development, evidence-based practices, and prototyping) that have been overlooked in prior SE research. Our findings extend and deepen the research into SE strategies and offer a comprehensive model of SE strategies that advances theory, practice and policy making.

  15. Isolating social influences on vulnerability to earthquake shaking: identifying cost-effective mitigation strategies.

    NASA Astrophysics Data System (ADS)

    Bhloscaidh, Mairead Nic; McCloskey, John; Pelling, Mark; Naylor, Mark

    2013-04-01

    Until expensive engineering solutions become more universally available, the objective targeting of resources at demonstrably effective, low-cost interventions might help reverse the trend of increasing mortality in earthquakes. Death tolls in earthquakes are the result of complex interactions between physical effects, such as the exposure of the population to strong shaking, and the resilience of the exposed population along with supporting critical infrastructures and institutions. The identification of socio-economic factors that contribute to earthquake mortality is crucial to identifying and developing successful risk management strategies. Here we develop a quantitative methodology more objectively to assess the ability of communities to withstand earthquake shaking, focusing on, in particular, those cases where risk management performance appears to exceed or fall below expectations based on economic status. Using only published estimates of the shaking intensity and population exposure for each earthquake, data that is available for earthquakes in countries irrespective of their level of economic development, we develop a model for mortality based on the contribution of population exposure to shaking only. This represents an attempt to remove, as far as possible, the physical causes of mortality from our analysis (where we consider earthquake engineering to reduce building collapse among the socio-economic influences). The systematic part of the variance with respect to this model can therefore be expected to be dominated by socio-economic factors. We find, as expected, that this purely physical analysis partitions countries in terms of basic socio-economic measures, for example GDP, focusing analytical attention on the power of economic measures to explain variance in observed distributions of earthquake risk. The model allows the definition of a vulnerability index which, although broadly it demonstrates the expected income-dependence of vulnerability to

  16. 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.

  17. Nurturing Mathematical Promise in a Regular Elementary Classroom: Exploring the Role of the Teacher and Classroom Environment

    ERIC Educational Resources Information Center

    Dimitriadis, Christos

    2016-01-01

    This article presents findings from a case study of an in-classroom program based on ability grouping for Year 2 (ages 6-7) primary (elementary) children identified as high ability in mathematics. The study examined the role of classroom setting, classroom environment, and teacher's approach in realizing and developing mathematical promise. The…

  18. Downregulated Glia Interplay and Increased miRNA-155 as Promising Markers to Track ALS at an Early Stage.

    PubMed

    Cunha, Carolina; Santos, Catarina; Gomes, Cátia; Fernandes, Adelaide; Correia, Alexandra Marçal; Sebastião, Ana Maria; Vaz, Ana Rita; Brites, Dora

    2018-05-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause. Absence of specific targets and biomarkers compromise the development of new therapeutic strategies and of innovative tools to stratify patients and assess their responses to treatment. Here, we investigate changes in neuroprotective-neuroinflammatory actions in the spinal cord of SOD1 G93A mice, at presymptomatic and symptomatic stages to identify stage-specific biomarkers and potential targets. Results showed that in the presymptomatic stage, there are alterations in both astrocytes and microglia, which comprise decreased expression of GFAP and S100B and upregulation of GLT-1, as well as reduced expression of CD11b, M2-phenotype markers, and a set of inflammatory mediators. Reduced levels of Connexin-43, Pannexin-1, CCL21, and CX3CL1 further indicate the existence of a compromised intercellular communication. In contrast, in the symptomatic stage, increased markers of inflammation became evident, such as NF-κB/Nlrp3-inflammasome, Iba1, pro-inflammatory cytokines, and M1-polarizion markers, together with a decreased expression of M2-phenotypic markers. We also observed upregulation of the CX3CL1-CX3CR1 axis, Connexin-43, Pannexin-1, and of microRNAs (miR)-124, miR-125b, miR-146a and miR-21. Reduced motor neuron number and presence of reactive astrocytes with decreased GFAP, GLT-1, and GLAST further characterized this inflammatory stage. Interestingly, upregulation of miR-155 and downregulation of MFG-E8 appear as consistent biomarkers of both presymptomatic and symptomatic stages. We hypothesize that downregulated cellular interplay at the early stages may represent neuroprotective mechanisms against inflammation, SOD1 aggregation, and ALS onset. The present study identified a set of inflamma-miRNAs, NLRP3-inflammasome, HMGB1, CX3CL1-CX3CR1, Connexin-43, and Pannexin-1 as emerging candidates and promising pharmacological targets that may represent potential

  19. Systematic approach identifies RHOA as a potential biomarker therapeutic target for Asian gastric cancer

    PubMed Central

    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

    2016-01-01

    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. PMID:27806312

  20. Integrative biology approach identifies cytokine targeting strategies for psoriasis.

    PubMed

    Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O

    2014-02-12

    Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.

  1. Enhancement of antitumor activity of gammaretrovirus carrying IL-12 gene through genetic modification of envelope targeting HER2 receptor: a promising strategy for bladder cancer therapy.

    PubMed

    Tsai, Y-S; Shiau, A-L; Chen, Y-F; Tsai, H-T; Tzai, T-S; Wu, C-L

    2010-01-01

    The objective of this study was to develop an HER2-targeted, envelope-modified Moloney murine leukemia virus (MoMLV)-based gammaretroviral vector carrying interleukin (IL)-12 gene for bladder cancer therapy. It displayed a chimeric envelope protein containing a single-chain variable fragment (scFv) antibody to the HER2 receptor and carried the mouse IL-12 gene. The fragment of anti-erbB2scFv was constructed into the proline-rich region of the viral envelope of the packaging vector lacking a transmembrane subunit of the carboxyl terminal region of surface subunit. As compared with envelope-unmodified gammaretroviruses, envelope-modified ones had extended viral tropism to human HER2-expressing bladder cancer cell lines, induced apoptosis, and affected cell cycle progression despite lower viral titers. Moreover, animal studies showed that envelope-modified gammaretroviruses carrying IL-12 gene exerted higher antitumor activity in terms of retarding tumor growth and prolonging the survival of tumor-bearing mice than unmodified ones, which were associated with enhanced tumor cell apoptosis as well as increased intratumoral levels of IL-12, interferon-gamma, IL-1beta, and tumor necrosis factor-alpha proteins. Therefore, the antitumor activity of gammaretroviruses carrying the IL-12 gene was enhanced through genetic modification of the envelope targeting HER2 receptor, which may be a promising strategy for bladder cancer therapy.

  2. A strategy for evaluating pathway analysis methods.

    PubMed

    Yu, Chenggang; Woo, Hyung Jun; Yu, Xueping; Oyama, Tatsuya; Wallqvist, Anders; Reifman, Jaques

    2017-10-13

    Researchers have previously developed a multitude of methods designed to identify biological pathways associated with specific clinical or experimental conditions of interest, with the aim of facilitating biological interpretation of high-throughput data. Before practically applying such pathway analysis (PA) methods, we must first evaluate their performance and reliability, using datasets where the pathways perturbed by the conditions of interest have been well characterized in advance. However, such 'ground truths' (or gold standards) are often unavailable. Furthermore, previous evaluation strategies that have focused on defining 'true answers' are unable to systematically and objectively assess PA methods under a wide range of conditions. In this work, we propose a novel strategy for evaluating PA methods independently of any gold standard, either established or assumed. The strategy involves the use of two mutually complementary metrics, recall and discrimination. Recall measures the consistency of the perturbed pathways identified by applying a particular analysis method to an original large dataset and those identified by the same method to a sub-dataset of the original dataset. In contrast, discrimination measures specificity-the degree to which the perturbed pathways identified by a particular method to a dataset from one experiment differ from those identifying by the same method to a dataset from a different experiment. We used these metrics and 24 datasets to evaluate six widely used PA methods. The results highlighted the common challenge in reliably identifying significant pathways from small datasets. Importantly, we confirmed the effectiveness of our proposed dual-metric strategy by showing that previous comparative studies corroborate the performance evaluations of the six methods obtained by our strategy. Unlike any previously proposed strategy for evaluating the performance of PA methods, our dual-metric strategy does not rely on any ground truth

  3. A Synthesis of Language Learning Strategies: Current Issues, Problems and Claims Made in Learner Strategy Research

    ERIC Educational Resources Information Center

    Barjesteh, Hamed; Mukundan, Jayakaran; Vaseghi, Reza

    2014-01-01

    The current paper presented theoretical assumptions behind language learning strategies (LLS) and an overview of methods used to identify learners' strategies, first, and then summarized what have been reported from large number of descriptive studies of strategies by language learners. Moreover, the paper tried to present the variety of…

  4. "URM candidates are encouraged to apply": a national study to identify effective strategies to enhance racial and ethnic faculty diversity in academic departments of medicine.

    PubMed

    Peek, Monica E; Kim, Karen E; Johnson, Julie K; Vela, Monica B

    2013-03-01

    There is little evidence regarding which factors and strategies are associated with high proportions of underrepresented minority (URM) faculty in academic medicine. The authors conducted a national study of U.S. academic medicine departments to better understand the challenges, successful strategies, and predictive factors for enhancing racial and ethnic diversity among faculty (i.e., physicians with an academic position or rank). This was a mixed-methods study using quantitative and qualitative methods. The authors conducted a cross-sectional study of eligible departments of medicine in 125 accredited U.S. medical schools, dichotomized into low-URM (bottom 50%) versus high-URM rank (top 50%). They used t tests and chi-squared tests to compare departments by geographic region, academic school rank, city type, and composite measures of "diversity best practices." The authors also conducted semistructured in-depth interviews with a subsample from the highest- and lowest-quartile medical schools in terms of URM rank. Eighty-two medical schools responded (66%). Geographic region and academic rank were statistically associated with URM rank, but not city type or composite measures of diversity best practices. Key themes emerged from interviews regarding successful strategies for URM faculty recruitment and retention, including institutional leadership, the use of human capital and social relationships, and strategic deployment of institutional resources. Departments of medicine with high proportions of URM faculty employ a number of successful strategies and programs for recruitment and retention. More research is warranted to identify new successful strategies and to determine the impact of specific strategies on establishing and maintaining workforce diversity.

  5. Phosphate-Linked Silibinin Dimers (PLSd): New Promising Modified Metabolites.

    PubMed

    Romanucci, Valeria; Gravante, Raffaele; Cimafonte, Martina; Marino, Cinzia Di; Mailhot, Gilles; Brigante, Marcello; Zarrelli, Armando; Fabio, Giovanni Di

    2017-08-11

    By exploiting the regioselective protection of the hydroxyl groups of silibinin along with the well-known phosphoramidite chemistry, we have developed an efficient strategy for the synthesis of new silibinin-modified species, which we have named Phosphate-Linked Silibinin Dimers (PLSd), in which the monomer units are linked by phosphodiester bonds. The antioxidant abilities of the new PLSd were estimated on HepG2 cells using DPPH free radical scavenging and xanthine/xanthine oxidase assays. The new phosphate-metabolites showed a higher anti-oxidant activity than the silibinin, as well as very low toxicity. The ability to scavenge reactive oxygen species (ROS) such as singlet oxygen () and hydroxyl radical () reveals that the two dimers are able to scavenge about two times more effectively than silibinin. Finally, solubility studies have shown that the PLSd present good water solubility (more than 20 mg·L -1 ) under circumneutral pH values, whereas the silibinin was found to be very poorly soluble (less than 0.4 mg·L -1 ) and not stable under alkaline conditions. Together, the above promising results warrant further investigation of the future potential of the PLSd as anti-oxidant metabolites within the large synthetic polyphenols field.

  6. Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease.

    PubMed

    Venigalla, Madhuri; Sonego, Sandra; Gyengesi, Erika; Sharman, Matthew J; Münch, Gerald

    2016-05-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by deposition of amyloid plaques and neurofibrillary tangles, as well as microglial and astroglial activation, and, finally, leading to neuronal dysfunction and death. Current treatments for AD primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for the treatment of AD patients. This review will provide an overview of the antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of a variety of nutraceuticals including curcumin, apigenin, docosahexaenoic acid, epigallocatechin gallate, α-lipoic acid and resveratrol and their potential for AD prevention and treatment. We suggest that therapeutic use of these compounds might lead to a safe strategy to delay the onset of AD or slow down its progression. The continuing investigation of the potential of these substances is necessary as they are promising compounds to yield a possible remedy for this pervasive disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Differences in the Policies, Programs, and Practices (PPPs) and Combination of PPPs across Turnaround, Moderately Improving, and Not Improving Schools

    ERIC Educational Resources Information Center

    Herman, Rebecca; Huberman, Mette

    2012-01-01

    The TALPS study aims to build on the existing research base to develop promising methodologies to identify chronically low-performing and turnaround schools, as well as to identify promising strategies for turning around chronically low-performing schools. By looking specifically at schools identified as turnaround, in comparison to nonturnaround…

  8. Screening strategies for tubal factor subfertility.

    PubMed

    den Hartog, J E; Lardenoije, C M J G; Severens, J L; Land, J A; Evers, J L H; Kessels, A G H

    2008-08-01

    Different screening strategies exist to estimate the risk of tubal factor subfertility, preceding laparoscopy. Three screening strategies, comprising Chlamydia trachomatis IgG antibody testing (CAT), high-sensitivity C-reactive protein (hs-CRP) testing and hysterosalpingography (HSG), were explored using laparoscopy as reference standard and the occurrence of a spontaneous pregnancy as a surrogate marker for the absence of tubal pathology. In this observational study, 642 subfertile women, who underwent tubal testing, participated. Data on serological testing, HSG, laparoscopy and interval conception were collected. Multiple imputations were used to compensate for missing data. Strategy A (HSG) has limited value in estimating the risk of tubal pathology. Strategy B (CAT-->HSG) shows that CAT significantly discerns patients with a high versus low risk of tubal pathology, whereas HSG following CAT has no additional value. Strategy C (CAT-->hs-CRP-->HSG) demonstrates that hs-CRP may be valuable in CAT-positive patients only and HSG has no additional value. CAT is proposed as first screening test for tubal factor subfertility. In CAT-negative women, HSG may be performed because of its high specificity and fertility-enhancing effect. In CAT-positive women, hs-CRP seems promising, whereas HSG has no additional value. The position and timing of laparoscopy deserves critical reappraisal.

  9. Macrolides: a promising pharmacologic therapy for chronic obstructive pulmonary disease

    PubMed Central

    Qiu, Shilin; Zhong, Xiaoning

    2016-01-01

    Chronic inflammation plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, there are no effective anti-inflammatory pharmacologic therapies available for COPD so far. Recent evidence suggests that an immunologic mechanism has a role in the pathogenesis of COPD. Macrolides possess anti-inflammatory and immune-modulating effects may be helpful in the treatment of COPD. Several clinical studies have shown that long-term use of macrolides reduces the frequency of COPD exacerbations. However, the subgroups that most effectively respond to long-term treatment of macrolides still need to be determined. The potential adverse events to individuals and the microbial resistance in community populations raises great concern on the long-term use of macrolides. Thus, novel macrolides have anti-inflammatory and immuno-modulating effects, but without antibiotic effects, and are promising as an anti-inflammatory agent for the treatment of COPD. In addition, the combination of macrolides and other anti-inflammatory pharmacologic agents may be a new strategy for the treatment of COPD. PMID:28030992

  10. 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.

  11. Mining Social Entrepreneurship Strategies Using Topic Modeling

    PubMed Central

    2016-01-01

    Despite the burgeoning research on social entrepreneurship (SE), SE strategies remain poorly understood. Drawing on extant research on the social activism and social change, empowerment and SE models, we explore, classify and validate the strategies used by 2,334 social entrepreneurs affiliated with the world’s largest SE support organization, Ashoka. The results of the topic modeling of the social entrepreneurs’ strategy profiles reveal that they employed a total of 39 change-making strategies that vary across resources (material versus symbolic strategies), specificity (general versus specific strategies), and mode of participation (mass versus elite participation strategies); they also vary across fields of practice and time. Finally, we identify six meta-SE strategies―a reduction from the 39 strategies―and identify four new meta-SE strategies (i.e., system reform, physical capital development, evidence-based practices, and prototyping) that have been overlooked in prior SE research. Our findings extend and deepen the research into SE strategies and offer a comprehensive model of SE strategies that advances theory, practice and policy making. PMID:26998970

  12. PSO-MISMO modeling strategy for multistep-ahead time series prediction.

    PubMed

    Bao, Yukun; Xiong, Tao; Hu, Zhongyi

    2014-05-01

    Multistep-ahead time series prediction is one of the most challenging research topics in the field of time series modeling and prediction, and is continually under research. Recently, the multiple-input several multiple-outputs (MISMO) modeling strategy has been proposed as a promising alternative for multistep-ahead time series prediction, exhibiting advantages compared with the two currently dominating strategies, the iterated and the direct strategies. Built on the established MISMO strategy, this paper proposes a particle swarm optimization (PSO)-based MISMO modeling strategy, which is capable of determining the number of sub-models in a self-adaptive mode, with varying prediction horizons. Rather than deriving crisp divides with equal-size s prediction horizons from the established MISMO, the proposed PSO-MISMO strategy, implemented with neural networks, employs a heuristic to create flexible divides with varying sizes of prediction horizons and to generate corresponding sub-models, providing considerable flexibility in model construction, which has been validated with simulated and real datasets.

  13. 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-...

  14. RNA-Seq reveals seven promising candidate genes affecting the proportion of thick egg albumen in layer-type chickens.

    PubMed

    Wan, Yi; Jin, Sihua; Ma, Chendong; Wang, Zhicheng; Fang, Qi; Jiang, Runshen

    2017-12-22

    Eggs with a much higher proportion of thick albumen are preferred in the layer industry, as they are favoured by consumers. However, the genetic factors affecting the thick egg albumen trait have not been elucidated. Using RNA sequencing, we explored the magnum transcriptome in 9 Rhode Island white layers: four layers with phenotypes of extremely high ratios of thick to thin albumen (high thick albumen, HTA) and five with extremely low ratios (low thick albumen, LTA). A total of 220 genes were differentially expressed, among which 150 genes were up-regulated and 70 were down-regulated in the HTA group compared with the LTA group. Gene Ontology (GO) analysis revealed that the up-regulated genes in HTA were mainly involved in a wide range of regulatory functions. In addition, a large number of these genes were related to glycosphingolipid biosynthesis, focal adhesion, ECM-receptor interactions and cytokine-cytokine receptor interactions. Based on functional analysis, ST3GAL4, FUT4, ITGA2, SDC3, PRLR, CDH4 and GALNT9 were identified as promising candidate genes for thick albumen synthesis and metabolism during egg formation. These results provide new insights into the molecular mechanisms of egg albumen traits and may contribute to future breeding strategies that optimise the proportion of thick egg albumen.

  15. [Advances of consolidated bioprocessing based on recombinant strategy].

    PubMed

    Zheng, Zongbao; Zhao, Meina; Chen, Tao; Zhao, Xueming

    2013-10-01

    Lignocellulosic biomass represents an abundant, low-cost and renewable source of potentially fermentable sugars. It is acandidate besides petroleum as feedstock for fuel and chemical production. Recent researches on utilizing lignocellulosicsas feedstock boost development of numerous-promising processes for a variety of fuels and chemicals, such as biodiesel, biohydrogen and ethanol. However, high cost in depolymerization is a primary obstacle preventing the use of lignocellulosic biomass as feedstock. Consolidated bioprocessing (CBP), refers to the bioprocess without any exogenous cellulolyotic enzymes added, converting the lignocellulosic material into biochemicals directly, which could potentially avoid the cost of the dedicated enzyme generation step by incorporating enzyme-generating, biomass-degrading and bioproduct-producing capabilities into a single organism through genetic engineering. There are two CBP strategies, native strategy and recombinant strategy. We mainly introduce the recombinant strategy, including its principle, the two responding styles, the contributions of synthetic biology and metabolic engineering and the future challenges.

  16. 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

  17. An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case

    PubMed Central

    Wong, Anthony F; Pielmeier, Ulrike; Haug, Peter J; Andreassen, Steen

    2016-01-01

    Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive

  18. A Delphi Study: Identifying Strategies That Promote Student Self-Efficacy in the Middle Level Mathematics Classroom

    ERIC Educational Resources Information Center

    Kieschnick, Lauren E.

    2013-01-01

    This dissertation examines the strategies that promote mathematical self-efficacy in the middle level mathematics classroom. The need for more self-efficacious students to pursue mathematics is prevalent in the United States due to the need of workers in the STEM fields. Finding strategies to promote mathematical self-efficacy will provide…

  19. In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni

    PubMed Central

    Neves, Bruno J.; Braga, Rodolpho C.; Bezerra, José C. B.; Cravo, Pedro V. L.; Andrade, Carolina H.

    2015-01-01

    Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries. Because praziquantel is the only drug in therapeutic use, the risk of drug resistance is a concern. In the search for new schistosomicidal drugs, we performed a target-based chemogenomics screen of a dataset of 2,114 proteins to identify drugs that are approved for clinical use in humans that may be active against multiple life stages of Schistosoma mansoni. Each of these proteins was treated as a potential drug target, and its amino acid sequence was used to interrogate three databases: Therapeutic Target Database (TTD), DrugBank and STITCH. Predicted drug-target interactions were refined using a combination of approaches, including pairwise alignment, conservation state of functional regions and chemical space analysis. To validate our strategy, several drugs previously shown to be active against Schistosoma species were correctly predicted, such as clonazepam, auranofin, nifedipine, and artesunate. We were also able to identify 115 drugs that have not yet been experimentally tested against schistosomes and that require further assessment. Some examples are aprindine, gentamicin, clotrimazole, tetrabenazine, griseofulvin, and cinnarizine. In conclusion, we have developed a systematic and focused computer-aided approach to propose approved drugs that may warrant testing and/or serve as lead compounds for the design of new drugs against schistosomes. PMID:25569258

  20. An adaptive sharing elitist evolution strategy for multiobjective optimization.

    PubMed

    Costa, Lino; Oliveira, Pedro

    2003-01-01

    Almost all approaches to multiobjective optimization are based on Genetic Algorithms (GAs), and implementations based on Evolution Strategies (ESs) are very rare. Thus, it is crucial to investigate how ESs can be extended to multiobjective optimization, since they have, in the past, proven to be powerful single objective optimizers. In this paper, we present a new approach to multiobjective optimization, based on ESs. We call this approach the Multiobjective Elitist Evolution Strategy (MEES) as it incorporates several mechanisms, like elitism, that improve its performance. When compared with other algorithms, MEES shows very promising results in terms of performance.

  1. Challenges and perspective of drug repurposing strategies in early phase clinical trials.

    PubMed

    Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

    2015-01-01

    Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

  2. Change Strategies and Associated Implementation Challenges: An Analysis of Online Counselling Sessions.

    PubMed

    Rodda, Simone N; Hing, Nerilee; Hodgins, David C; Cheetham, Alison; Dickins, Marissa; Lubman, Dan I

    2017-09-01

    Self-change is the most frequent way people limit or reduce gambling involvement and often the first choice of people experiencing gambling-related problems. Less well known is the range of change strategies gamblers use and how these are selected, initiated or maintained. This study examined change strategies discussed in counselling transcripts from 149 clients who accessed a national online gambling help service in Australia. Using thematic analysis, we identified the presence of six change strategies; cash control and financial management, social support, avoiding or limiting gambling, alternative activities, changing thoughts and beliefs, and self-assessment and monitoring. Four implementation issues were also identified; a mismatch between need and strategy selection or maintenance; importance and readiness versus the cost of implementation; poor or unplanned transitions between strategies; and failure to review the helpfulness of strategies resulting in premature abandonment or unhelpful prolonged application. This study is the first to identify change strategies discussed in online counselling sessions. This study suggests change strategies are frequently discussed in online counselling sessions and we identified multiple new actions associated with change strategies that had not previously been identified. However, multiple implementation issues were identified and further work is required to determine the helpfulness of change strategies in terms of their selection, initiation and maintenance.

  3. An Autoethnographical Analysis of a School Leader: Informing Strategies to Improve Educational Outcomes for Children of Promise Schools

    ERIC Educational Resources Information Center

    Lincoln, Carleton

    2013-01-01

    Recent research suggests a major crisis exists affecting urban children's educational opportunities. This study focuses on the use of research-based strategies to determine whether, and to what extent, transformative leadership influences the development of quality education that overcomes educational inequity in the lives of students who attend…

  4. The Promise and Pitfalls of Grand Strategy

    DTIC Science & Technology

    2012-08-01

    others, Thomas Friedman, “Rethinking Foreign Affairs,” The New York Times, February 7, 1992; R. W. Apple, “The Sense of Triumph Fades, Uncertainty and...1947, Box 146, James Forrestal Papers, Seeley Mudd Manuscript Library (SMML), Princeton University. 39. Kennan National War College Lecture

  5. Reframing Retention Strategy: A Focus on Promise

    ERIC Educational Resources Information Center

    Kalsbeek, David H.

    2013-01-01

    At every college and university, students enroll with expectations and aspirations about the kind of experience and the kind of outcomes that the institution delivers. When those expectations are met and exceeded, students are satisfied and likely to remain committed to their college choice. When their experience falls short of their expectations,…

  6. Hydrogen: A Promising Fuel and Energy Storage Solution - Continuum

    Science.gov Websites

    Magazine | NREL Hydrogen: A Promising Fuel and Energy Storage Solution Fuel cell electric Ainscough, NREL Hydrogen: A Promising Fuel and Energy Storage Solution Electrolysis-generated hydrogen may provide a solution to fluctuations in renewable-sourced energy. As electricity from renewable resources

  7. Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases.

    PubMed

    Al-Bari, Md Abdul Alim

    2017-02-01

    Emerging viruses such as HIV, dengue, influenza A, SARS coronavirus, Ebola, and other viruses pose a significant threat to human health. Majority of these viruses are responsible for the outbreaks of pathogenic lethal infections. To date, there are no effective therapeutic strategies available for the prophylaxis and treatment of these infections. Chloroquine analogs have been used for decades as the primary and most successful drugs against malaria. Concomitant with the emergence of chloroquine-resistant Plasmodium strains and a subsequent decrease in the use as antimalarial drugs, other applications of the analogs have been investigated. Since the analogs have interesting biochemical properties, these drugs are found to be effective against a wide variety of viral infections. As antiviral action, the analogs have been shown to inhibit acidification of endosome during the events of replication and infection. Moreover, immunomodulatory effects of analogs have been beneficial to patients with severe inflammatory complications of several viral diseases. Interestingly, one of the successful targeting strategies is the inhibition of HIV replication by the analogs in vitro which are being tested in several clinical trials. This review focuses on the potentialities of chloroquine analogs for the treatment of endosomal low pH dependent emerging viral diseases.

  8. The Ontario Food and Nutrition Strategy: identifying indicators of food access and food literacy for early monitoring of the food environment.

    PubMed

    Boucher, Beatrice A; Manafò, Elizabeth; Boddy, Meaghan R; Roblin, Lynn; Truscott, Rebecca

    2017-09-01

    To address challenges Canadians face within their food environments, a comprehensive, multistakeholder, intergovernmental approach to policy development is essential. Food environment indicators are needed to assess population status and change. The Ontario Food and Nutrition Strategy (OFNS) integrates the food, agriculture and nutrition sectors, and aims to improve the health of Ontarians through actions that promote healthy food systems and environments. This report describes the process of identifying indicators for 11 OFNS action areas in two strategic directions (SDs): Healthy Food Access, and Food Literacy and Skills. The OFNS Indicators Advisory Group used a five-step process to select indicators: (1) potential indicators from national and provincial data sources were identified; (2) indicators were organized by SD, action area and data type; (3) selection criteria were identified, pilot tested and finalized; (4) final criteria were applied to refine the indicator list; and (5) indicators were prioritized after reapplication of selection criteria. Sixty-nine potential indicators were initially identified; however, many were individual-level rather than system-level measures. After final application of the selection criteria, one individual-level indicator and six system-level indicators were prioritized in five action areas; for six of the action areas, no indicators were available. Data limitations suggest that available data may not measure important aspects of the food environment, highlighting the need for action and resources to improve system-level indicators and support monitoring of the food environment and health in Ontario and across Canada.

  9. Promising strategies for advancement in knowledge of suicide risk factors and prevention.

    PubMed

    Sareen, Jitender; Isaak, Corinne; Katz, Laurence Y; Bolton, James; Enns, Murray W; Stein, Murray B

    2014-09-01

    Suicide is an important public health problem. Although there have been advances in our knowledge of suicide, gaps remain in knowledge about suicide risk factors and prevention. Here, we discuss research pathways that have the potential to rapidly advance knowledge in suicide risk assessment and reduction of suicide deaths over the next decade. We provide a concise overview of the methodologic approaches that have the capacity to rapidly increase knowledge and change practice, which have been successful in past work in psychiatry and other areas of medicine. We suggest three specific pathways to advance knowledge of suicide risk factors and prevention. First, analysis of large-scale epidemiologic surveys and administrative data sets can advance the understanding of suicide. Second, given the low base rate of suicide, there is a need for networks/consortia of investigators in the field of suicide prevention. Such consortia have the capacity to analyze existing epidemiologic data sets, create multi-site cohort studies of high-risk groups to increase knowledge of biological and other risk factors, and create a platform for multi-site clinical trials. Third, partnerships with policymakers and researchers would facilitate careful scientific evaluation of policies and programs aimed at reducing suicide. Suicide intervention policies are often multifaceted, expensive, and rarely evaluated. Using quasi-experimental methods or sophisticated analytic strategies such as propensity score-matching techniques, the impact of large-scale interventions on suicide can be evaluated. Furthermore, such partnerships between policymakers and researchers can lead to the design and support of prospective RCTs (e.g., cluster randomized trials, stepped wedge designs, waiting list designs) in high-risk groups (e.g., people with a history of suicide attempts, multi-axial comorbidity, and offspring of people who have died by suicide). These research pathways could lead to rapid knowledge uptake

  10. Insecticide Resistance and Management Strategies in Urban Ecosystems

    PubMed Central

    Zhu, Fang; Lavine, Laura; O’Neal, Sally; Lavine, Mark; Foss, Carrie; Walsh, Douglas

    2016-01-01

    The increased urbanization of a growing global population makes imperative the development of sustainable integrated pest management (IPM) strategies for urban pest control. This emphasizes pests that are closely associated with the health and wellbeing of humans and domesticated animals. Concurrently there are regulatory requirements enforced to minimize inadvertent exposures to insecticides in the urban environment. Development of insecticide resistance management (IRM) strategies in urban ecosystems involves understanding the status and mechanisms of insecticide resistance and reducing insecticide selection pressure by combining multiple chemical and non-chemical approaches. In this review, we will focus on the commonly used insecticides and molecular and physiological mechanisms underlying insecticide resistance in six major urban insect pests: house fly, German cockroach, mosquitoes, red flour beetle, bed bugs and head louse. We will also discuss several strategies that may prove promising for future urban IPM programs. PMID:26751480

  11. Beyond the Folklore: A Strategy for Identifying Quality Undergraduate Colleges

    ERIC Educational Resources Information Center

    Conrad, Clinton F.

    2012-01-01

    College and university quality--what it is and how to identify it--is a preoccupation of many prospective college students and their parents, high school counselors, and college admission personnel. Regardless of class, race, and gender, it is no longer enough for a growing number of individuals simply to attend college: matriculating at an…

  12. 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

  13. Solar-Terrestrial Science Strategy Workshop

    NASA Technical Reports Server (NTRS)

    Banks, Peter M. (Editor); Roberts, William T. (Editor); Kropp, Jack (Editor)

    1989-01-01

    The conclusions and recommendations reached at the Solar Terrestrial Science Strategy Workshop are summarized. The charter given to this diverse group was: (1) to establish the level of scientific understanding to be accomplished with the completion of the current and near term worldwide programs; (2) identify the significant scientific questions to be answered by future solar terrestrial programs, and the programs required to answer these questions; and (3) map out a program strategy, taking into consideration currently perceived space capabilities and constraints, to accomplish the identified program.

  14. 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.

  15. Using appreciative inquiry to help students identify strategies to overcome handicaps of their learning styles.

    PubMed

    Kumar, Latha Rajendra; Chacko, Thomas Vengail

    2012-01-01

    In India, as in some other neighboring Asian countries, students and teachers are generally unaware of the differences in the learning styles among learners, which can handicap students with learning styles alien to the common teaching/learning modality within the institution. This study aims to find out whether making students aware of their learning styles and then using the Appreciative Inquiry approach to help them discover learning strategies that worked for them and others with similar learning styles within the institution made them perceive that this experience improved their learning and performance in exams. The visual, auditory, read-write, and kinesthetic (VARK) inventory of learning styles questionnaire was administered to all 100 first-year medical students of the Father Muller's Medical College in Mangalore India to make them aware of their individual learning styles. An Appreciate Inquiry intervention was administered to 62 student volunteers who were counseled about the different learning styles and their adaptive strategies. Pre and post intervention change in student's perception about usefulness of knowing learning styles on their learning, learning behavior, and performance in examinations was collected from the students using a prevalidated questionnaire. Post intervention mean scores showed a significant change (P < 0.0001) in student's self-perceptions about usefulness of knowing one's learning style and discovering strategies that worked within the institutional environment. There was agreement among students that the intervention helped them become more confident in learning (84%), facilitating learning in general (100%), and in understanding concepts (100%). However, only 29% of the students agreed that the intervention has brought about their capability improvement in application of learning and 31% felt it improved their performance in exams. Appreciate Inquiry was perceived as useful in helping students discover learning strategies

  16. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

    PubMed

    Planer, Joseph D; Hulverson, Matthew A; Arif, Jennifer A; Ranade, Ranae M; Don, Robert; Buckner, Frederick S

    2014-07-01

    An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper) have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's) in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM), a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM), and an antifolate drug (pyrimethamine, EC50 of 3.8 µM) and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

  17. Synergy Testing of FDA-Approved Drugs Identifies Potent Drug Combinations against Trypanosoma cruzi

    PubMed Central

    Ranade, Ranae M.; Don, Robert; Buckner, Frederick S.

    2014-01-01

    An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper) have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's) in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM), a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM), and an antifolate drug (pyrimethamine, EC50 of 3.8 µM) and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease. PMID:25033456

  18. Integrated Decision Strategies for Skin Sensitization Hazard

    PubMed Central

    Strickland, Judy; Zang, Qingda; Kleinstreuer, Nicole; Paris, Michael; Lehmann, David M.; Choksi, Neepa; Matheson, Joanna; Jacobs, Abigail; Lowit, Anna; Allen, David; Casey, Warren

    2016-01-01

    One of the top priorities of ICCVAM is the identification and evaluation of non-animal alternatives for skin sensitization testing. Although skin sensitization is a complex process, the key biological events of the process have been well characterized in an adverse outcome pathway (AOP) proposed by OECD. Accordingly, ICCVAM is working to develop integrated decision strategies based on the AOP using in vitro, in chemico, and in silico information. Data were compiled for 120 substances tested in the murine local lymph node assay (LLNA), direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT), and KeratinoSens assay. Data for six physicochemical properties that may affect skin penetration were also collected, and skin sensitization read-across predictions were performed using OECD QSAR Toolbox. All data were combined into a variety of potential integrated decision strategies to predict LLNA outcomes using a training set of 94 substances and an external test set of 26 substances. Fifty-four models were built using multiple combinations of machine learning approaches and predictor variables. The seven models with the highest accuracy (89–96% for the test set and 96–99% for the training set) for predicting LLNA outcomes used a support vector machine (SVM) approach with different combinations of predictor variables. The performance statistics of the SVM models were higher than any of the non-animal tests alone and higher than simple test battery approaches using these methods. These data suggest that computational approaches are promising tools to effectively integrate data sources to identify potential skin sensitizers without animal testing. PMID:26851134

  19. Strategy Formation in an Adhocracy.

    ERIC Educational Resources Information Center

    Mintzberg, Henry; McHugh, Alexandra

    1985-01-01

    This paper identifies and tracks the strategies pursued by a single-project organization, the National Film Board, across almost four decades of its history. Findings focus on three themes: the emergent nature of the organization's strategies, its cycles of behavior, and the organization's quest for "adhocracy." (TE)

  20. Promising Behavior Change Techniques in a Multicomponent Intervention to Reduce Concerns about Falls in Old Age: A Delphi Study

    ERIC Educational Resources Information Center

    Vestjens, Lotte; Kempen, Gertrudis I. J. M.; Crutzen, Rik; Kok, Gerjo; Zijlstra, G. A. Rixt

    2015-01-01

    Complex behavior change interventions need evidence regarding the effectiveness of individual components to understand how these interventions work. The objective of this study was to identify the least and most promising behavior change techniques (BCTs) within the Dutch intervention "A Matter of Balance" (AMB-NL) aimed at concerns…