[Perspectives and challenges of malaria vaccine. Why we must do more].

PubMed

Leroy, Odile

2007-10-01

During the last 10 years the development of a malaria vaccine has attracted an increasing amount of attention both from the political sector and from financial investors. This has led to a number of major scientific and technological advances, but much remains to be done. Numerous potential target antigens are under investigation, and most research is focusing on a subunit vaccine. Irradiated attenuated sporozoites are also a promising approach, even if major technological and regulatory challenges remain to be overcome. Barriers to vaccine development include an inadequate understanding of certain aspects of host-parasite biology and protective immune responses. Other challenges are to increase the antigenicity of some antigens, and to optimize the quality of the immune response. However, research funding remains the main obstacle.

The Challenge of Education: No Time To Waste, No Room, for Failure.

ERIC Educational Resources Information Center

Cuban American National Council, Inc.

This paper summarizes issues and perspectives that form the basis of current educational debate. The paper contends that early in the 21st century, Hispanics and other minorities will constitute the majority of the work force in major markets across the nation. The lack of preparedness of over half the potential pool of minority workers will have…

Adapting to climate change at Olympic National Forest and Olympic National Park

Treesearch

Jessica E. Halofsky; David L. Peterson; Kathy A. O’Halloran; Catherine Hawkins Hoffman

2011-01-01

Climate change presents a major challenge to natural resource managers both because of the magnitude of potential effects of climate change on ecosystem structure, processes, and function, and because of the uncertainty associated with those potential ecological effects. Concrete ways to adapt to climate change are needed to help natural resource managers take the...

Multiscale Simulations of Protein Landscapes: Using Coarse Grained Models as Reference Potentials to Full Explicit Models

PubMed Central

Messer, Benjamin M.; Roca, Maite; Chu, Zhen T.; Vicatos, Spyridon; Kilshtain, Alexandra Vardi; Warshel, Arieh

2009-01-01

Evaluating the free energy landscape of proteins and the corresponding functional aspects presents a major challenge for computer simulation approaches. This challenge is due to the complexity of the landscape and the enormous computer time needed for converging simulations. The use of simplified coarse grained (CG) folding models offers an effective way of sampling the landscape but such a treatment, however, may not give the correct description of the effect of the actual protein residues. A general way around this problem that has been put forward in our early work (Fan et al, Theor Chem Acc (1999) 103:77-80) uses the CG model as a reference potential for free energy calculations of different properties of the explicit model. This method is refined and extended here, focusing on improving the electrostatic treatment and on demonstrating key applications. This application includes: evaluation of changes of folding energy upon mutations, calculations of transition states binding free energies (which are crucial for rational enzyme design), evaluation of catalytic landscape and simulation of the time dependent responses to pH changes. Furthermore, the general potential of our approach in overcoming major challenges in studies of structure function correlation in proteins is discussed. PMID:20052756

In-Space Assembly Capability Assessment for Potential Human Exploration and Science Applications

NASA Technical Reports Server (NTRS)

Jefferies, Sharon A.; Jones, Christopher A.; Arney, Dale C.; Stillwagen, Frederic H.; Chai, Patrick R.; Hutchinson, Craig D.; Stafford, Matthew A.; Moses, Robert W.; Dempsey, James A.; Rodgers, Erica M.;

Student's plagiarism--a challenge for paramedic educators.

PubMed

Lass, Piotr; Bandurski, Tomasz; Swietlik, Dariusz; Tomczak, Hanna; Wengler, Lubomira

2006-01-01

Student's plagiarism is a growing problem not only in the writing of controlling essays, but above all in the writing in BSc./MSc. diploma theses, which sometimes can be simply bought from ghost-writers. This is a major challenge for medical educators, particularly in paramedic professions. The aim of this paper is to overview the frequency of plagiarism among students, the factors influencing plagiarism, the ways of detecting it and potential countermeasures.

Integration of internationally educated nurses into the U.S. Workforce.

PubMed

Wolcott, Krista; Llamado, Suzanne; Mace, Denise

2013-01-01

This study describes the integration experiences of internationally educated nurses, managers, and educators working in Northern California. The purpose of this qualitative pilot study was to explore the experiences of internationally educated nurses and the nurse managers and educators working with them, to understand the issues, and to highlight potential solutions for addressing integration challenges. Through interviews and qualitative analysis, successful strategies and persistent challenges were identified. Major themes identified included communication difficulties; financial challenges; the need for outside social support; and educational orientations focused on culture, nurse role, and communication techniques.

New approaches to the representation and analysis of phenotype knowledge in human diseases and their animal models.

PubMed

Schofield, Paul N; Sundberg, John P; Hoehndorf, Robert; Gkoutos, Georgios V

2011-09-01

The systematic investigation of the phenotypes associated with genotypes in model organisms holds the promise of revealing genotype-phenotype relations directly and without additional, intermediate inferences. Large-scale projects are now underway to catalog the complete phenome of a species, notably the mouse. With the increasing amount of phenotype information becoming available, a major challenge that biology faces today is the systematic analysis of this information and the translation of research results across species and into an improved understanding of human disease. The challenge is to integrate and combine phenotype descriptions within a species and to systematically relate them to phenotype descriptions in other species, in order to form a comprehensive understanding of the relations between those phenotypes and the genotypes involved in human disease. We distinguish between two major approaches for comparative phenotype analyses: the first relies on evolutionary relations to bridge the species gap, while the other approach compares phenotypes directly. In particular, the direct comparison of phenotypes relies heavily on the quality and coherence of phenotype and disease databases. We discuss major achievements and future challenges for these databases in light of their potential to contribute to the understanding of the molecular mechanisms underlying human disease. In particular, we discuss how the use of ontologies and automated reasoning can significantly contribute to the analysis of phenotypes and demonstrate their potential for enabling translational research.

Circadian rhythmicity as a predictor of weight-loss effectiveness

USDA-ARS?s Scientific Manuscript database

Some of the major challenges associated with successful dietary weight management include the identification of individuals not responsive to specific interventions. The aim was to investigate the potential relationship between weight loss and circadian rhythmicity, using wrist temperature and actim...

Nanomedicine for safe healing of bone trauma: Opportunities and challenges

PubMed Central

Behzadi, Shahed; Luther, Gaurav A.; Harris, Mitchel B.; Farokhzad, Omid C.; Mahmoudi, Morteza

2017-01-01

Historically, high-energy extremity injuries resulting in significant soft-tissue trauma and bone loss were often deemed unsalvageable and treated with primary amputation. With improved soft-tissue coverage and nerve repair techniques, these injuries now present new challenges in limb-salvage surgery. High-energy extremity trauma is pre-disposed to delayed or unpredictable bony healing and high rates of infection, depending on the integrity of the soft-tissue envelope. Furthermore, orthopedic trauma surgeons are often faced with the challenge of stabilizing and repairing large bony defects while promoting an optimal environment to prevent infection and aid bony healing. During the last decade, nanomedicine has demonstrated substantial potential in addressing the two major issues intrinsic to orthopedic traumas (i.e., high infection risk and low bony reconstruction) through combatting bacterial infection and accelerating/increasing the effectiveness of the bone-healing process. This review presents an overview and discusses recent challenges and opportunities to address major orthopedic trauma through nanomedical approaches. PMID:28918266

The Enduring Health Challenges of Afghan Immigrants and Refugees in Iran: A Systematic Review

PubMed Central

Hosseini Divkolaye, Nasim Sadat; Burkle, Frederick M.

2017-01-01

Introduction Iran is the third country in the world with the highest number of registered refugees with the majority coming from Afghanistan. They suffer major health and social risks yet their health status has never been comprehensively determined. Methods This systematic review of the literature highlights major disparities among documented immigrants in health access, communicable and non-communicable diseases and the increasingly desperate plight of undocumented immigrants. Results Comparing with Iranian population, the findings suggest the higher prevalence of most diseases among Afghan immigrants and refugees. This highlights the importance of increasing the migrants' access to health services from both public health as well as human rights perspectives. Discussion Although the Iranian government has taken new initiatives to overcome this challenge, certain issues have still remained unaddressed. Potential solutions to improve this process are discussed. PMID:28856065

Challenges in Bio-fabrication of Organoid Cultures.

PubMed

Peng, Weijie; Datta, Pallab; Wu, Yang; Dey, Madhuri; Ayan, Bugra; Dababneh, Amer; Ozbolat, Ibrahim T

2018-06-01

Three-dimensional (3D) organoids have shown advantages in cell culture over traditional two-dimensional (2D) culture, and have great potential in various applications of tissue engineering. However, there are limitations in current organoid fabrication technologies, such as uncontrolled size, poor reproductively, and inadequate complexity of organoids. In this chapter, we present the existing techniques and discuss the major challenges for 3D organoid biofabrication. Future perspectives on organoid bioprinting are also discussed, where bioprinting technologies are expected to make a major contribution in organoid fabrication, such as realizing mass production and constructing complex heterotypic tissues, and thus further advance the translational application of organoids in tissue engineering and regenerative medicine as well drug testing and pharmaceutics.

Preliminary identification of potential markets for off-grid electrification: tool development and a case study of Ghana

NASA Astrophysics Data System (ADS)

Descoqs, Benoit; Bhattacharyya, Subhes

2018-02-01

With more than one billion people lacking access to electricity in the world, ensuring universal access to electricity by 2030 remains a major challenge which cannot be left to the government initiatives alone. Access to local information and identification of potential areas for investment can be a challenge for investors. This paper provides a tool for preliminary assessment of potential markets for off-grid electrification in developing countries and applies this to Ghana to demonstrate its applicability. A multi-criteria approach is used to rank the districts according to the overall potential and the best markets and least favourable areas for investment are identified. The tool offers flexibility to include new inputs to the analysis and the factor weights can be adjusted as appropriate. The case study shows that the tool can effectively identify potential areas from a list of candidates and offers support to analysts.

ELISA microarray technology as a high-throughput system for cancer biomarker validation

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

Zangar, Richard C.; Daly, Don S.; White, Amanda M.

A large gap currently exists between the ability to discover potential biomarkers and the ability to assess the real value of these proteins for cancer screening. One major challenge in biomarker validation is the inherent variability in biomarker levels. This variability stems from the diversity across the human population and the considerable molecular heterogeneity between individual tumors, even those that originate from a single tissue. Another major challenge with cancer screening is that most cancers are rare in the general population, meaning that the specificity of an assay must be very high if the number of false positive is notmore » going to be much greater than the number of true positives. Because of these challenges with biomarker validation, it is necessary to analysis of thousands of samples before a clear idea of the utility of a screening assay can be determined. Enzyme-linked immunosorbent assay (ELISA) microarray technology can simultaneously quantify levels of multiple proteins and has the potential to accelerate biomarker validation. In this review, we discuss current ELISA microarray technology and the enabling advances needed to achieve the reproducibility and throughput that are required to evaluate cancer biomarkers.« less

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

USGS Publications Warehouse

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

2015-01-01

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

Data Sources for Prioritizing Human Exposure to Chemicals

EPA Science Inventory

Humans may be exposed to thousands of chemicals through contact in the workplace, home, and via air, water, food, and soil. A major challenge is estimating chemical exposures, which requires understanding potential exposure pathways directly related to how chemicals are used. Wit...

Education and Telecommunications: Partners in Progress.

ERIC Educational Resources Information Center

Kitchen, Will

America's rural communities are facing increasing challenges to the provision of equitable services and economic stability. Two major rural concerns are the lack of educational opportunities and resources and potentially inadequate telecommunications infrastructures for economic development. In order to attain economic and educational parity with…

The potential for a new era of supersonic and hypersonic aviation

NASA Technical Reports Server (NTRS)

Harris, Roy V.

1990-01-01

A new era of supersonic and hypersonic aviation is envisioned. The potential for supersonic and hypersonic flight vehicles in this new era is analyzed. Technology challenges that must be met in order to bring in this new era of flight are discussed. The current technical status and future potential are cited in the areas of aerodynamics, propulsion, and structural materials. A next major step in the development of high-speed air transportation is suggested.

Climate Change and Health in the Urban Context: The Experience of Barcelona.

PubMed

Villalbí, Joan R; Ventayol, Irma

2016-07-01

Climate change poses huge challenges for public health, and cities are at the forefront of this process. The purpose of this paper is to present the issues climate change poses for public health in the city of Barcelona, how they are being addressed, and what are the current major challenges, trying to contribute to the development of a baseline understanding of the status of adaptation in cities from a public health perspective. The major issues related to climate change faced by the city are common to other urban centers in a Mediterranean climate: heat waves, water availability and quality, air quality, and diseases transmitted by vectors, and all are reviewed in detail with empirical data. They are not a potential threat for the future, but have actually challenged the city services and infrastructure over the last years, requiring sustainable responses and rigorous planning. © The Author(s) 2016.

Conservation biology in Asia: the major policy challenges.

PubMed

McNeely, Jeffrey A; Kapoor-Vijay, Promila; Zhi, Lu; Olsvig-Whittaker, Linda; Sheikh, Kashif M; Smith, Andrew T

2009-08-01

With about half the world's human population and booming economies, Asia faces numerous challenges to its biodiversity. The Asia Section of the Society for Conservation Biology has identified some key policy issues in which significant progress can be made. These include developing new sources of funding for forest conservation; identifying potential impacts of energy alternatives on the conservation of biodiversity; curbing the trade in endangered species of plants and animals; a special focus on the conservation of mountain biodiversity; enhancing relevant research; ensuring that conservation biology contributes to major international conventions and funding mechanisms; using conservation biology to build a better understanding of zoonotic diseases; more effectively addressing human-animal conflicts; enhancing community-based conservation; and using conservation biology to help address the pervasive water-deficit problems in much of Asia. These challenges can be met through improved regional cooperation among the relevant stakeholders.

Safety Challenges and Improvement Strategies of Ethnic Minority Construction Workers: A Case Study in Hong Kong.

PubMed

Wu, Chunlin; Luo, Xiaowei; Wang, Tao; Wang, Yue; Sapkota, Bibek

2018-04-18

Due to cultural differences, ethnic minority construction workers are more difficult to manage and more vulnerable to accidents. This study aims to identify the major barriers faced by ethnic minority workers from their own perspectives and determine potential strategies to enhance safety climate of construction projects, thus ultimately improve their safety performance. A survey with modified Nordic safety climate questionnaire was conducted in a certain sub-contractor in Hong Kong. In-depth interviews, status quo description, major challenge investigation and safety knowledge tests were carried as well. The top three most important safety challenges identified are improper stereotypes from the whole industry, lack of opportunities for job assignment, and language barriers. To improve the safety performance, employers should allocate sufficient personal protective equipment and governments should organize unannounced site visits more frequently. Besides, the higher-level management should avoid giving contradictory instructions to foremen against to the standards of supervisors.

Toxicological challenges to microbial bioethanol production and strategies for improved tolerance

DOE PAGES

Akinsho, Hannah; Rydzak, Thomas; Borole, Abhijeet P.; ...

2015-09-30

Bioethanol production output has increased steadily over the last two decades and is now beginning to become competitive with traditional liquid transportation fuels due to advances in engineering, the identification of new production host organisms, and the development of novel biodesign strategies. A significant portion of these efforts has been dedicated to mitigating the toxicological challenges encountered across the bioethanol production process. From the release of potentially cytotoxic or inhibitory compounds from input feedstocks, through the metabolic co-synthesis of ethanol and potentially detrimental byproducts, and to the potential cytotoxicity of ethanol itself, each stage of bioethanol production requires the applicationmore » of genetic or engineering controls that ensure the host organisms remain healthy and productive to meet the necessary economies required for large scale production. In addition, as production levels continue to increase, there is an escalating focus on the detoxification of the resulting waste streams to minimize their environmental impact. Thus, this review will present the major toxicological challenges encountered throughout each stage of the bioethanol production process and the commonly employed strategies for reducing or eliminating potential toxic effects.« less

Regulatory challenges for autologous tissue engineered products on their way from bench to bedside in Europe.

PubMed

Ram-Liebig, Gouya; Bednarz, Juergen; Stuerzebecher, Burkard; Fahlenkamp, Dirk; Barbagli, Guido; Romano, Giuseppe; Balsmeyer, Ulf; Spiegeler, Maria-Elsa; Liebig, Soeren; Knispel, Helmut

2015-03-01

Since the late eighties of last century the high potential of tissue engineered products (TEP)s has been shown for the treatment of various diseases and many scientific publications appeared in this field. However, only few products reached the market since. Development of TEPs is a promising but owing to its novelty a very challenging task that requires experts in this still developing field as well as ample financial resources. This paper summarises relevant regulatory challenges during quality, preclinical and clinical development of autologous TEPs in Europe. Selected strategies on how to manage major issues are presented, together with some examples from the development of an autologous TEP for urethroplasty. Considering these aspects may help other investigators with potential strategies during the development of novel TEPs. Copyright © 2014 Elsevier B.V. All rights reserved.

Social Work Grand Challenges: Leaders' Perceptions of the Potential for Partnering with Business.

PubMed

Long, Ashley

2018-04-23

Social work's ability to address complex societal problems such as those identified in the American Academy of Social Work and Social Welfare's Grand Challenges for Social Work is reliant on being innovative in how we prepare social workers and how we collaborate with others, including business. This research seeks to understand how leaders of major social work organizations perceive potential partnership with the business sector-including both possible threats and opportunities. Interviews were conducted with those serving on the Council on Social Work Education's Leadership Roundtable. The research explores how emerging partnership models can be helpful and ways in which the profession can prepare practitioners for better partnering with the business sector. Qualitative findings identify four key strategies to address the grand challenges and enhance partnerships: (1) more interdisciplinary work is needed, (2) social work students need to be adequately equipped for collaborative work, (3) a cohesive message is needed from the field, and (4) the potential benefits for partnering with business outweigh the risks.

Rainwater harvesting in South Africa: Challenges and opportunities

NASA Astrophysics Data System (ADS)

Mwenge Kahinda, J.; Taigbenu, A. E.

Water paucity remains a major threat to poverty, hunger alleviation as well as sustainable development. Innovative water technologies such as rainwater harvesting (RWH) have the potential to improve rural water supply and contribute to the provision of the first 6 kl of water consumed monthly. RWH can also be the solution to South Africa food security by increasing water productivity of dryland agriculture and enabling homestead gardening. Although used for decades in South Africa, rainwater harvesting (RWH) is still far from being utilised to its full potential as unresolved challenges prevent its wide scale adoption. The paper presents the challenges and opportunities to the upscaling of RWH in South Africa. Key challenges preventing the nationwide expansion of RWH are the current water related legislations, the lack of finances and the absence of a national umbrella body that coordinates. While opportunities lie in the worth of knowledge gathered by research projects, funded over the last two decades, on the biophysical and socio-economic impacts of RWH.

Deceased organ donation for transplantation: Challenges and opportunities

PubMed Central

Girlanda, Raffaele

2016-01-01

Organ transplantation saves thousands of lives every year but the shortage of donors is a major limiting factor to increase transplantation rates. To allow more patients to be transplanted before they die on the wait-list an increase in the number of donors is necessary. Patients with devastating irreversible brain injury, if medically suitable, are potential deceased donors and strategies are needed to successfully convert them into actual donors. Multiple steps in the process of deceased organ donation can be targeted to increase the number of organs suitable for transplant. In this review, after describing this process, we discuss current challenges and potential strategies to expand the pool of deceased donors. PMID:27683626

Evaluating the effect of microalgal biomass on soil-plant-water systems

USDA-ARS?s Scientific Manuscript database

Exploring all possible applications of microalgal biomass is crucial to strengthen the current algal industry and reducing the environmental impacts of agriculture is a major global challenge. Microalgae can play a progressive role as they have the potential to improve soil structure, reduce erosion...

Exploring consumer pathways and patterns of use for chemicals in the environment

EPA Science Inventory

Background: Humans may be exposed to thousands of chemicals through contact in the workplace, home, and via air, water, food, and soil. A major challenge is estimating exposures to these chemicals, which requires understanding potential exposure routes directly related to how che...

Current Challenges and Potential Opportunities for the Pharmaceutical Sciences to Make Global Impact: An FIP Perspective.

PubMed

Tucker, Geoffrey; DeSilva, Binodh; Dressman, Jennifer; Ito, Michiho; Kumamoto, Takuya; Mager, Don; Mahler, Hanns-Christian; Maitland-van der Zee, Anke H; Pauletti, Giovanni M; Sasaki, Hitoshi; Shah, Vinod; Tang, Daniel; Ward, Michael

2016-09-01

The chairs of each of the 8 Special Interest Groups of the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation have compiled opinions with regard to major challenges for the pharmaceutical sciences over the next 5-10 years. Areas covered are drug design and discovery, natural products, formulation design and pharmaceutical technology, pharmacokinetics/pharmacodynamics and systems pharmacology, translational and personalized medicine, biotechnology, analytical sciences and quality control, and regulatory science. Copyright © 2016. Published by Elsevier Inc.

Changing practice: implications of the World Report on Disability for responding to communication disability in under-served populations.

PubMed

Wylie, Karen; McAllister, Lindy; Davidson, Bronwyn; Marshall, Julie

2013-02-01

The World Report on Disability provides a major challenge to the conceptualization and delivery of services for people with communication disabilities around the world. Many people, in both Majority and Minority World countries, receive limited or no support in relation to their communication disability. In this paper the prevalence of communication disability across the world (and the challenges to obtaining these data) are discussed, particularly in relation to disability more broadly. Populations that are under-served by speech-language pathology services in both Majority and Minority World countries are described. The paper describes organizational change theory and the potential it has, together with a biopsychosocial model of disability, to assist in understanding and influencing development of relevant services for people with communication disabilities (PWCD), particularly those who are under-served. Aspects of, and influences on, service delivery for PWCD are described. The need for novel ways of conceptualizing development of services, including population-based approaches, is highlighted. Finally, the challenges and opportunities for PWCD and for speech-language pathologists which arise from the nine recommendations of the World Report on Disability are considered and readers are encouraged to consider new and novel ways of developing equitable services for people with communication disabilities, in both majority and minority world settings.

Trials and tribulations: how we established a major incident database.

PubMed

Hardy, S E J; Fattah, S

2017-01-25

We describe the process of setting up a database of major incident reports and its potential future application. A template for reporting on major incidents was developed using a consensus-based process involving a team of experts in the field. A website was set up as a platform from which to launch the template and as a database of submitted reports. This paper describes the processes involved in setting up a major incident reporting database. It describes how specific difficulties have been overcome and anticipates challenges for the future. We have successfully set up a major incident database, the main purpose of which is to have a repository of standardised major incident reports that can be analysed and compared in order to learn from them.

Possibility of Exosome-Based Therapeutics and Challenges in Production of Exosomes Eligible for Therapeutic Application.

PubMed

Yamashita, Takuma; Takahashi, Yuki; Takakura, Yoshinobu

2018-01-01

Exosomes are cell-derived vesicles with a diameter 30-120 nm. Exosomes contain endogenous proteins and nucleic acids; delivery of these molecules to exosome-recipient cells causes biological effects. Exosomes derived from some types of cells such as mesenchymal stem cells and dendritic cells have therapeutic potential and may be biocompatible and efficient agents against various disorders such as organ injury. However, there are many challenges for the development of exosome-based therapeutics. In particular, producing exosomal formulations is the major barrier for therapeutic application because of their heterogeneity and low productivity. Development and optimization of producing methods, including methods for isolation and storage of exosome formulations, are required for realizing exosome-based therapeutics. In addition, improvement of therapeutic potential and delivery efficiency of exosomes are important for their therapeutic application. In this review, we summarize current knowledge about therapeutic application of exosomes and discuss some challenges in their successful use.

Advancing Massage Therapy Research Competencies: Dimensions for Thought and Action.

ERIC Educational Resources Information Center

Hymel, Glenn M.

Two major developments in the therapeutic massage and bodywork profession have recently brought to the forefront the issue of research competencies. The profession has been called to a potentially heightened level of credibility. One challenge to the profession's development is that of coordinating the various curricular, instructional,…

Is U.S. climatic diversity well represented within the existing federal protection network?

Treesearch

Enric Batllori; Carol Miller; Marc-Andre Parisien; Sean A. Parks; Max A. Moritz

2014-01-01

Establishing protection networks to ensure that biodiversity and associated ecosystem services persist under changing environments is a major challenge for conservation planning. The potential consequences of altered climates for the structure and function of ecosystems necessitates new and complementary approaches be incorporated into traditional conservation plans....

The Challenge of Formative Assessment in Mathematics Education: Children's Minds, Teachers' Minds

ERIC Educational Resources Information Center

Ginsburg, Herbert P.

2009-01-01

The developmental psychology of mathematical thinking and the clinical interview method can make major contributions to education by transforming the process of formative assessment--the attempt to use information concerning student performance, knowledge, learning potential, and motivation to inform instruction. The clinical interview is a…

Potential geographic distribution of Palmer amaranth under current and future climates

USDA-ARS?s Scientific Manuscript database

Herbicide resistant weeds are increasingly becoming a major challenge for agricultural production worldwide. Palmer amaranth is an invasive annual forb that has recently emerged as one of the most widespread and severe agronomic weeds in the US, due in part to its facility for evolving herbicide res...

The Sweat Lodge Ceremony in Challenge/Adventure Programming.

ERIC Educational Resources Information Center

Quinn, William J.; Smith, Thomas E.

This paper advocates the potentials of "sweat lodge" rituals for adventure education programs. Historically, rituals and ceremonies have been instrumental in passing major philosophical and sociological paradigms from one generation to the next. However, there is little theory and research about how ritual and ceremony results in the…

Design and Performance of a Xenobiotic Metabolism Database Manager for Building Metabolic Pathway Databases

EPA Science Inventory

A major challenge for scientists and regulators is accounting for the metabolic activation of chemicals that may lead to increased toxicity. Reliable forecasting of chemical metabolism is a critical factor in estimating a chemical’s toxic potential. Research is underway to develo...

Do bioflavonoids in Juniperus virginiana heartwood stimulate oviposition in the ladybird Coleomegilla maculata?

USDA-ARS?s Scientific Manuscript database

Maximizing the reproductive potential of ladybird beetles fed factitious foods or artificial diets, in lieu of natural prey, is a major challenge to cost-effective mass-rearing for augmentative biological control. In this study, we tested the hypothesis that compounds in redcedar, Juniperus (J.) vir...

76 FR 77260 - Proposed Information Collection Request (ICR) for the Evaluation of the Unemployment Compensation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-12

... Unemployment Compensation Provisions of the American Recovery and Reinvestment Act of 2009; Comment Request... major challenges for the U.S. system of unemployment compensation (UC). For example, sharply increasing lengths of unemployment spells prompted Federal legislation that extended the potential duration of UC...

The Instrument of the Future: Computers in Education.

ERIC Educational Resources Information Center

Leonard, Rex; LeCroy, Barbara

Before computers will be able to fulfill their potential in education, two major challenges must be overcome--the lack of well-trained teachers and a lack of general knowledge about software and its capabilities. Teachers must acquire some computer literacy skills, including programming, word processing, materials generation and record keeping. In…

"Hedge Your Bets": Technology's Role in Young Gay Men's Relationship Challenges.

PubMed

McKie, Raymond M; Milhausen, Robin R; Lachowsky, Nathan J

2017-01-01

Technology is playing an increasingly pervasive role among young gay men in the process of meeting potential romantic or sexual partners. We investigated challenges posed by technology related to young gay men's relationships. Focus groups (n = 9) of young gay men aged 18-24 (n = 43) were transcribed verbatim, and thematic analysis was used to identify two major themes regarding challenges to relationship development and maintenance. Subthemes include unrealistic expectations of relationships, inauthentic self-presentation online, sexual primacy over romance, increased opportunities for infidelity, and jealousy. The implications of this study for sexual education and sexual health promotion are discussed.

Special Report: E-Waste Management in the United States and Public Health Implications.

PubMed

Seeberger, Jessica; Grandhi, Radhika; Kim, Stephani S; Mase, William A; Reponen, Tiina; Ho, Shuk-mei; Chen, Aimin

2016-10-01

Electronic waste (e-waste) generation is increasing worldwide, and its management becomes a significant challenge because of the many toxicants present in electronic devices. The U.S. is a major producer of e-waste, although its management practice and policy regulation are not sufficient to meet the challenge. We reviewed e-waste generation, current management practices and trends, policy challenges, potential health impact, and toxicant exposure prevention in the U.S. A large amount of toxic metals, flame retardants, and other persistent organic pollutants exist in e-waste or can be released from the disposal of e-waste (e.g., landfill, incineration, recycling). Landfill is still a major method used to dispose of obsolete electronic devices, and only about half of the states have initiated a landfill ban for e-waste. Recycling of e-waste is an increasing trend in the past few years. There is potential, however, for workers to be exposed to a mixture of toxicants in e-waste and these exposures should be curtailed. Perspectives and recommendations are provided regarding managing e-waste in the U.S. to protect public health, including enacting federal legislation, discontinuing landfill disposal, protecting workers in recycling facilities from toxicant exposure, reducing toxicant release into the environment, and raising awareness of this growing environmental health issue among the public.

Current Challenges for HTCMC Aero-Propulsion Components

NASA Technical Reports Server (NTRS)

DiCarlo, James A.; Bansal, Narottam P.

2007-01-01

In comparison to the best metallic materials, HTCMC aero-propulsion engine components offer the opportunity of reduced weight and higher temperature operation, with corresponding improvements in engine cooling requirements, emissions, thrust, and specific fuel consumption. Although much progress has been made in the development of advanced HTCMC constituent materials and processes, major challenges still remain for their implementation into these components. The objectives of this presentation are to briefly review (1) potential HTCMC aero-propulsion components and their generic material performance requirements, (2) recent progress at NASA and elsewhere concerning advanced constituents and processes for meeting these requirements, (3) key HTCMC component implementation challenges that are currently being encountered, and (4) on-going activities within the new NASA Fundamental Aeronautics Program that are addressing these challenges.

Challenges in the management of community pharmacies in Malaysia

PubMed Central

2017-01-01

Background: The provision of professional pharmacy services by community pharmacists continues to be limited, particularly in low and middle income countries. It was postulated that multiple management challenges faced by community pharmacists contribute to this situation. Objective: The primary aim of the research was to determine the challenges faced in the management of community pharmacies in Sarawak (the largest state in Malaysia), and practical strategies to cope and overcome the challenges. Methods: Semi-structured interviews were carried out with community pharmacists practising in Sarawak. Purposive and snowball sampling were employed to ensure a diverse group of informants. The interviews were audio-recorded and transcribed verbatim, with the resultant data analysed using thematic analysis. Data collection, coding, interpretation were carried out iteratively until theoretical saturation. Results: Twenty respondents from different demographic characteristics were recruited. Six major themes were identified. Management challenges faced by community pharmacists traverse five major domains: market competition, legislative issues, customers’ knowledge and expectations, macroeconomic impacts and operational challenges. Most of these challenges require government intervention to be resolved. In the meantime, improving customer service and expanding the range of professional services were seen as the most viable strategies to cope with existing challenges. The main concern is that current legislative and economic landscape may hinder these strategies. Enactment of dispensing separation and more protective measures against market competition were suggested to alleviate the challenges faced. Conclusion: Numerous management challenges faced by community pharmacists that distract them from delivering professional pharmacy services have been highlighted. Urgent affirmative actions by the government are warranted in supporting community pharmacists to realise and maximise their potentials. PMID:28690697

Advances in selective activation of muscles for non-invasive motor neuroprostheses.

PubMed

Koutsou, Aikaterini D; Moreno, Juan C; Del Ama, Antonio J; Rocon, Eduardo; Pons, José L

2016-06-13

Non-invasive neuroprosthetic (NP) technologies for movement compensation and rehabilitation remain with challenges for their clinical application. Two of those major challenges are selective activation of muscles and fatigue management. This review discusses how electrode arrays improve the efficiency and selectivity of functional electrical stimulation (FES) applied via transcutaneous electrodes. In this paper we review the principles and achievements during the last decade on techniques for artificial motor unit recruitment to improve the selective activation of muscles. We review the key factors affecting the outcome of muscle force production via multi-pad transcutaneous electrical stimulation and discuss how stimulation parameters can be set to optimize external activation of body segments. A detailed review of existing electrode array systems proposed by different research teams is also provided. Furthermore, a review of the targeted applications of existing electrode arrays for control of upper and lower limb NPs is provided. Eventually, last section demonstrates the potential of electrode arrays to overcome the major challenges of NPs for compensation and rehabilitation of patient-specific impairments.

Cough reflex testing with inhaled capsaicin and TRPV1 activation in asthma and comorbid conditions.

PubMed

Couto, M; de Diego, A; Perpiñi, M; Delgado, L; Moreira, A

2013-01-01

A high parasympathetic tone leading to bronchoconstriction and neurogenic inflammation is thought to have a major role in the pathogenesis of asthma. Transient receptor potential vanilloid 1 (TRPV1) is the hub of almost all neuronal inflammatory signaling pathways. A critical determinant of neurogenic inflammation, TRPV1 functions as a sensor for detecting irritants in the lung by transmitting noxious stimuli to the central nervous system and inducing the release of a variety of proinflammatory neuropeptides at the peripheral terminals. Challenge with inhaled capsaicin, an exogenous agonist of TRPV1, has been used to measure the sensitivity of the cough reflex. However, inhalation of capsaicin is also associated with parasympathetic bronchoconstriction, mucus hypersecretion, vasodilatation, and the sensation of dyspnea. Therefore, inhaled capsaicin challenge is expected to have other potential applications in asthma and comorbid conditions, such as rhinitis and gastroesophageal reflux disease, both of which produce cough. Capsaicin challenge has established itself as a useful objective method for evaluating airway hypersensitivity; however, it is potentially valuable in many other situations, which will be reviewed in this paper.

Some imminent but overlooked preanalytical and analytical challenges currently facing biomarkers and companion diagnostics.

PubMed

Halim, Abdel-Baset

2015-06-01

An incredibly high failure rate in the pharmaceutical industry has positioned personalized medicine with its prerequisite drug-diagnostic codevelopment, commonly known as companion diagnostics (CDx), in the frontline as an potential rescuer. This hopefulness is potentiated by the recent major advances and competitiveness in molecular diagnostics, making laboratory tests widely accessible at affordable prices. If executed correctly, biomarkers and CDx can potentially help the drug industry by enhancing the probability of success and possibly accelerating time to market; help the diagnostics industry develop tests utilizing precious, clinically annotated human samples; and, more importantly, benefit patients by supporting accurate diagnosis and selection of the most efficacious and least toxic therapies. However, this spectacular road is not yet paved, and it faces an enormous number of challenges. This paper will list these challenges and highlight some critical problems with representative examples of imminent but still overlooked preanalytical and analytical variables that can defeat the whole purpose of biomarkers and CDx and mislead drug developers and clinicians. The paper will provide some suggestions for mitigation. © 2015 New York Academy of Sciences.

An innovative survey design to understand sustainable travel behaviors : potential of a rolling sample survey to replace traditional household travel surveys.

DOT National Transportation Integrated Search

2014-10-01

We propose an innovative survey with rolling samples to address a major fiscal challenge faced by many MPOs. Faced with a small, but : continuous budget, MPOs are increasingly unable to continue the current survey practice: conducting a large survey ...

Coordinated pre-preemption of traffic signals to enhance railroad grade crossing safety in urban areas and estimation of train impacts to arterial travel time delay : [technical summary].

DOT National Transportation Integrated Search

2014-01-01

Rail lines present two major challenges to the : roadways they intersect: potential for collisions : and increased congestion. In addition, congestion : can contribute collision hazards when drivers are : impatient or vehicles are prevented from clea...

Support from Afar: Using Chemical Safety Information on the Internet.

ERIC Educational Resources Information Center

Stuart, Ralph

One of the major challenges facing people committed to Teaching Safety in High Schools, Colleges, and Universities is keeping up with both the wide range of relevant technical information about potential hazards (ranging from fire protection to chemical hazards to biological issues) and the ever-changing world of safety regulations and standards.…

A Guided Inquiry on Hubble Plots and the Big Bang

ERIC Educational Resources Information Center

Forringer, Ted

2014-01-01

In our science for non-science majors course "21st Century Physics," we investigate modern "Hubble plots" (plots of velocity versus distance for deep space objects) in order to discuss the Big Bang, dark matter, and dark energy. There are two potential challenges that our students face when encountering these topics for the…

Air Permitting Implications of a Biorefinery Producing Raw Bio-Oil in Comparison with Producing Gasoline and Diesel Blendstocks

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

Bhatt, Arpit H; Zhang, Yi Min

A biorefinery, considered a chemical process plant under the Clean Air Act permitting program, could be classified as a major or minor source based on the size of the facility and magnitude of regulated pollutants emitted. Our previous analysis indicates that a biorefinery using fast pyrolysis conversion process to produce finished gasoline and diesel blendstocks with a capacity of processing 2,000 dry metric tons of biomass per day would likely be classified as a major source because several regulated pollutants (such as particulate matter, sulfur dioxide, nitrogen oxide) are estimated to exceed the 100 tons per year (tpy) major sourcemore » threshold, applicable to chemical process plants. Being subject to a major source classification could pose additional challenges associated with obtaining an air permit in a timely manner before the biorefinery can start its construction. Recent developments propose an alternative approach to utilize bio-oil produced via the fast pyrolysis conversion process by shipping it to an existing petroleum refinery, where the raw bio-oil can be blended with petroleum-based feedstocks (e.g., vacuum gas oil) to produce gasoline and diesel blendstocks with renewable content. Without having to hydro-treat raw bio-oil, a biorefinery is likely to reduce its potential-to-emit to below the 100 tpy major source threshold, and therefore expedite its permitting process. We compare the PTE estimates for the two biorefinery designs with and without hydrotreating of bio-oils and examine the air permitting implications on potential air permit classification and discuss the best available control technology requirements for the major source biorefinery utilizing hydrotreating operation. Our analysis is expected to provide useful information to new biofuel project developers to identify opportunities to overcome challenges associated with air permitting.« less

Challenges of climate change

PubMed Central

Husaini, Amjad M

2014-01-01

Kashmir valley is a major saffron (Crocus sativus Kashmirianus) growing area of the world, second only to Iran in terms of production. In Kashmir, saffron is grown on uplands (termed in the local language as “Karewas”), which are lacustrine deposits located at an altitude of 1585 to 1677 m above mean sea level (amsl), under temperate climatic conditions. Kashmir, despite being one of the oldest historical saffron-producing areas faces a rapid decline of saffron industry. Among many other factors responsible for decline of saffron industry the preponderance of erratic rainfalls and drought-like situation have become major challenges imposed by climate change. Saffron has a limited coverage area as it is grown as a ‘niche crop’ and is a recognized “geographical indication,” growing under a narrow microclimatic condition. As such it has become a victim of climate change effects, which has the potential of jeopardizing the livelihood of thousands of farmers and traders associated with it. The paper discusses the potential and actual impact of climate change process on saffron cultivation in Kashmir; and the biotechnological measures to address these issues. PMID:25072266

Gene-environment interactions in geriatric depression.

PubMed

Lotrich, Francis E

2011-06-01

In older adults, several environmental challenges can potentially trigger the onset of an episode of major depression. Vulnerability to these challenges can be influenced by genetics. There is accumulating evidence for an interaction between stress and a serotonin transporter polymorphism, though there is also heterogeneity among studies. Other relevant genes include those encoding for the neuroendocrine stress axis, growth factors, and other monoaminergic systems. Each of these may interact with either predisposing traumas in early childhood or precipitating events later in life. Copyright © 2011 Elsevier Inc. All rights reserved.

The World Spatiotemporal Analytics and Mapping Project (WSTAMP): Discovering, Exploring, and Mapping Spatiotemporal Patterns Across Heterogenous Space-Time Data

NASA Astrophysics Data System (ADS)

Morton, A.; Stewart, R.; Held, E.; Piburn, J.; Allen, M. R.; McManamay, R.; Sanyal, J.; Sorokine, A.; Bhaduri, B. L.

2017-12-01

Spatiotemporal (ST) analytics applied to major spatio-temporal data sources from major vendors such as USGS, NOAA, World Bank and World Health Organization have tremendous value in shedding light on the evolution of physical, cultural, and geopolitical landscapes on a local and global level. Especially powerful is the integration of these physical and cultural datasets across multiple and disparate formats, facilitating new interdisciplinary analytics and insights. Realizing this potential first requires an ST data model that addresses challenges in properly merging data from multiple authors, with evolving ontological perspectives, semantical differences, changing attributes, and content that is textual, numeric, categorical, and hierarchical. Equally challenging is the development of analytical and visualization approaches that provide a serious exploration of this integrated data while remaining accessible to practitioners with varied backgrounds. The WSTAMP project at the Oak Ridge National Laboratory has yielded two major results in addressing these challenges: 1) development of the WSTAMP database, a significant advance in ST data modeling that integrates 16000+ attributes covering 200+ countries for over 50 years from over 30 major sources and 2) a novel online ST exploratory and analysis tool providing an array of modern statistical and visualization techniques for analyzing these data temporally, spatially, and spatiotemporally under a standard analytic workflow. We report on these advances, provide an illustrative case study, and inform how others may freely access the tool.

Food systems transition and disruptive low carbon innovation: implications for a food security research agenda.

PubMed

Tyfield, David

2011-07-01

There is a growing consensus that we are facing epochal challenges in global food security. Moreover, these challenges are multiple and complex. Meeting these challenges will involve nothing less than a wholesale socio-technical transition of the agri-food system. Optimizing the efficacy of the contribution of research to such a food security agenda will probably also need new institutional mechanisms and career structures to facilitate new kinds of collaborations and ongoing, longer-term projects. In short, the multiple challenges of food security demand a different political economy of research for effective intervention by science. In making this argument, the paper summarizes the major findings of a recent report regarding the potential impact of so-called 'disruptive' low-carbon innovations in China.

Major Management Challenges and Program Risks. Department of Education

DTIC Science & Technology

2001-01-01

GAO United States General Accounting Office Performance and Accountability SeriesJanuary 2001 Major Management Challenges and Program Risks ...34) Title and Subtitle Major Management Challenges and Program Risks Department of Education Contract or Grant Number Program Element Number Authors...Accountability Series: Major Management Challenges and Program Risks . In that series, GAO advised the Congress that it planned to reassess the

Psychiatric epidemiology: selected recent advances and future directions.

PubMed Central

Kessler, R. C.

2000-01-01

Reviewed in this article are selected recent advances and future challenges for psychiatric epidemiology. Major advances in descriptive psychiatric epidemiology in recent years include the development of reliable and valid fully structured diagnostic interviews, the implementation of parallel cross-national surveys of the prevalences and correlates of mental disorders, and the initiation of research in clinical epidemiology. Remaining challenges include the refinement of diagnostic categories and criteria, recognition and evaluation of systematic underreporting bias in surveys of mental disorders, creation and use of accurate assessment tools for studying disorders of children, adolescents, the elderly, and people in less developed countries, and setting up systems to carry out small area estimations for needs assessment and programme planning. Advances in analytical and experimental epidemiology have been more modest. A major challenge is for psychiatric epidemiologists to increase the relevance of their analytical research to their colleagues in preventative psychiatry as well as to social policy analysts. Another challenge is to develop interventions aimed at increasing the proportion of people with mental disorders who receive treatment. Despite encouraging advances, much work still needs to be conducted before psychiatric epidemiology can realize its potential to improve the mental health of populations. PMID:10885165

Book Analysis: Challenger: A Major Malfunction.

DTIC Science & Technology

1988-04-01

REPORT NUMBER 88-113S TITLE BOOK ANALYSIS: CHALLENGER : A MAJOR MALFUNCTION AUTHOR(S) MAJOR THOMAS M. HALL, USAF FACULTY ADVISOR LT COL JOhN R. GRELLMAN... CHALLENGER : A MAJOR MALFUNCTION 12. PERSONAL AUTHOR(S) Hall, Thomas M., Major, USAF 13a. TYPE OF REPORT 13b. TIME COVERED 14. DATE OF REPORT (Year, Month...identify by block number) FIELD GROUP SUB-GROUP 19. ABSTRACT Continue on reverse if necessary and identify by block number) This report analyzes Challenger

Exploring bacterial lignin degradation.

PubMed

Brown, Margaret E; Chang, Michelle C Y

2014-04-01

Plant biomass represents a renewable carbon feedstock that could potentially be used to replace a significant level of petroleum-derived chemicals. One major challenge in its utilization is that the majority of this carbon is trapped in the recalcitrant structural polymers of the plant cell wall. Deconstruction of lignin is a key step in the processing of biomass to useful monomers but remains challenging. Microbial systems can provide molecular information on lignin depolymerization as they have evolved to break lignin down using metalloenzyme-dependent radical pathways. Both fungi and bacteria have been observed to metabolize lignin; however, their differential reactivity with this substrate indicates that they may utilize different chemical strategies for its breakdown. This review will discuss recent advances in studying bacterial lignin degradation as an approach to exploring greater diversity in the environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

Ryan Hart; Troy Hiltbrand

Few areas in the economy have generated as much attention as big data and advanced analytics in recent years due to its potential of revolutionizing the way that business function in the coming years. One of the major challenges that organizations face in implementing analytics that have the potential of providing them a competitive advantage in the market is that of finding the elusive data scientist needed to execute on big data strategy. This article addresses what some business are doing to bridge that gap between vision and reality.

Salicylic acid-induced abiotic stress tolerance and underlying mechanisms in plants

PubMed Central

Khan, M. Iqbal R.; Fatma, Mehar; Per, Tasir S.; Anjum, Naser A.; Khan, Nafees A.

2015-01-01

Abiotic stresses (such as metals/metalloids, salinity, ozone, UV-B radiation, extreme temperatures, and drought) are among the most challenging threats to agricultural system and economic yield of crop plants. These stresses (in isolation and/or combination) induce numerous adverse effects in plants, impair biochemical/physiological and molecular processes, and eventually cause severe reductions in plant growth, development and overall productivity. Phytohormones have been recognized as a strong tool for sustainably alleviating adverse effects of abiotic stresses in crop plants. In particular, the significance of salicylic acid (SA) has been increasingly recognized in improved plant abiotic stress-tolerance via SA-mediated control of major plant-metabolic processes. However, the basic biochemical/physiological and molecular mechanisms that potentially underpin SA-induced plant-tolerance to major abiotic stresses remain least discussed. Based on recent reports, this paper: (a) overviews historical background and biosynthesis of SA under both optimal and stressful environments in plants; (b) critically appraises the role of SA in plants exposed to major abiotic stresses; (c) cross-talks potential mechanisms potentially governing SA-induced plant abiotic stress-tolerance; and finally (d) briefly highlights major aspects so far unexplored in the current context. PMID:26175738

Movement-Based Mathematics: Enjoyment and Engagement without Compromising Learning through the EASY Minds Program

ERIC Educational Resources Information Center

Riley, Nicholas; Lubans, David; Holmes, Kathryn; Hansen, Vibeke; Gore, Jennifer; Morgan, Philip

2017-01-01

There has been a worldwide decline in interest and achievement in mathematics in young people. Despite the extensive benefits of physical activity, the majority of children are not sufficiently active. Schools have the potential to arrest both concerns through innovative teaching that challenges and complements traditional approaches. The aim of…

Innovative manure treatments in the USA – state of the art (Tratamientos Innovadores de estiercoles en USA - estado del arte)

USDA-ARS?s Scientific Manuscript database

Currently, the potential impact of manure on the environment represents one of the world agriculture’s major challenges. Treatment technologies can play an important role in the management of livestock manure by providing a more flexible approach to land application and acreage limitations and by so...

Evaluating the sources of potential migrant species: implications under climate change

Treesearch

Ines Ibanez; James S. Clark; Michael C. Dietze

2008-01-01

As changes in climate become more apparent, ecologists face the challenge of predicting species responses to the new conditions. Most forecasts are based on climate envelopes (CE), correlative approaches that project future distributions on the basis of the current climate often assuming some dispersal lag. One major caveat with this approach is that it ignores the...

The Challenges of Planning Language Objectives in Content-Based ESL Instruction

ERIC Educational Resources Information Center

Baecher, Laura; Farnsworth, Tim; Ediger, Anne

2014-01-01

The purpose of this research was to investigate the major patterns in content-based instruction (CBI) lesson plans among practicum teachers at the final stage of an MA TESOL program. One hundred and seven lesson plans were coded according to a typology developed to evaluate clarity and identify areas of potential difficulty in the design of…

Vaccination of pigs with a codon-pair bias de-optimized live attenuated influenza vaccine protects from homologous challenge

USDA-ARS?s Scientific Manuscript database

Influenza A virus (IAV) in swine constitutes a major economic burden for producers as well as a potential threat to public health. Whole inactivated virus vaccines (WIV) are the predominant countermeasure employed to control IAV in swine herds in the United States despite the superior protection, an...

NASA-OAST program in photovoltaic energy conversion

NASA Technical Reports Server (NTRS)

Mullin, J. P.; Flood, D. J.

1982-01-01

The NASA program in photovoltaic energy conversion includes research and technology development efforts on solar cells, blankets, and arrays. The overall objectives are to increase conversion efficiency, reduce mass, reduce cost, and increase operating life. The potential growth of space power requirements in the future presents a major challenge to the current state of technology in space photovoltaic systems.

Using a Stance Corpus to Learn about Effective Authorial Stance-Taking: A Textlinguistic Approach

ERIC Educational Resources Information Center

Chang, Peichin

2012-01-01

Presenting a persuasive authorial stance is a major challenge for second language (L2) writers in writing academic research. Failure to present an effective authorial stance often results in poor evaluation, which compromises a writer's research potential. This study proposes a "textlinguistic" approach to advanced academic writing to complement a…

The Goals of Science Museums in the Eyes of Museum Pedagogical Staff

ERIC Educational Resources Information Center

Shaby, Neta; Ben-Zvi Assaraf, Orit; Tishler, Chagit E.

2016-01-01

Today, science is a major part of Western culture. One advantage of informal learning environments is that they are (potentially) open to a wide range of populations with varying levels of interest and knowledge. Because of their informal nature, documenting learning has proven challenging. Studies that assess learning in museums, therefore, must…

New monoclonal antibodies against a novel subtype of Shiga toxin 1 produced by Enterobacter cloacae and their use in analysis of human serum

USDA-ARS?s Scientific Manuscript database

Shiga toxin (Stx) is a major virulence factor for several bacterial pathogens that cause potentially fatal illness, including Escherichia coli and Shigella spp. The continual emergence of new subtypes of Stxs presents challenges in clinical diagnosis of infections caused by Shiga toxin-producing org...

Ongoing ostomy self-care challenges of long-term rectal cancer survivors.

PubMed

Bulkley, Joanna E; McMullen, Carmit K; Grant, Marcia; Wendel, Christopher; Hornbrook, Mark C; Krouse, Robert S

2018-05-29

Surgical treatment for rectal cancer (RC) can result in an intestinal ostomy that requires lifelong adaptation and investment of physical, cognitive, and financial resources. However, little is known about the extent of ongoing challenges related to ostomy self-care among long-term RC survivors. We analyzed the prevalence of self-reported ostomy self-care challenges and the physical and environmental factors that can support or undermine ostomy self-care. We mailed surveys to long-term (≥ 5 years post-diagnosis) RC survivors, including 177 adults with ostomies who were members of integrated health systems in northern California, Oregon, and Washington State. Potential participants were identified through tumor registries. Data were also extracted from electronic health records. The response rate was 65%. The majority of respondents were male (67%), and the mean age was 75 years. Sixty-three percent of respondents reported at least one ostomy self-care challenge. The most common challenges were leakage or skin problems around the ostomy and needing to change the pouching system too frequently. Twenty-two percent reported difficulty caring for their ostomy. Younger age and higher BMI were consistently related to ostomy self-care challenges. The majority of RC survivors reported ostomy-related self-care challenges, and 31% experienced problems across multiple domains of ostomy self-care. In addition, most survivors reported significant physical challenges that could lead to ostomy-related disability. Although the participants surveyed had access to ostomy care nurses, the care gaps we found suggest that additional work is needed to understand barriers to ostomy care, reduce unmet needs, and improve well-being among this group.

Challenges faced by multidisplinary new investigators on addressing grand challenges in global health.

PubMed

Logie, Carmen; Dimaras, Helen; Fortin, Anny; Ramón-García, Santiago

2014-04-15

The grand challenges approach aims to spark innovative and transformative strategies to overcome barriers to significant global health issues. Grand Challenges Canada endorses an 'Integrated Innovation™' approach that focuses on the intersection of scientific/technological, social and business innovation. In this article we explore themes emerging from a dialogue between the authors, who are multidisciplinary recipients of the 'Rising Stars in Global Health' award from Grand Challenges Canada, regarding benefits of engaging in integrated innovation research, and recommendations for how this approach may develop in the future. Our dialogue followed a semi-structured interview format that addressed three topics: 1) reflections on applying an Integrated Innovation™ approach for global health; 2) thoughts on participation in the Grand Challenges 2012 meeting; and 3) authors' visions of Grand Challenges Canada and the Grand Challenge movement towards 2020. The dialogue was transcribed verbatim and we used thematic analysis techniques to identify, analyze and report themes in the data. Benefits of working using the Grand Challenges approach centered on two themes: a) the potential for scientific breakthrough and b) building interdisciplinary collaborations and a community of scholars. Challenges and opportunities for Grand Challenges in moving forward included: a) capacity building, particularly regarding Integrated Innovation™ and scale-up planning; b) interdisciplinary and international mentorship for new investigators; and c) potential for future commercialization. Our discussion highlighted that Integrated Innovation™ offers the opportunity to develop new theories, methods and approaches to global health while simultaneously fostering a collaborative spirit grounded in international, interdisciplinary collaborations. However, the arguable over-emphasis on corporatization poses a major challenge for new investigators. We propose a more balanced way forward that can harness technology to foster mentorship across time and space to support the development of such skills and ideas among new investigators.

Regenerative Chemical Biology: Current Challenges and Future Potential

PubMed Central

Ao, Ada; Hao, Jijun; Hong, Charles C.

2011-01-01

The enthusiasm surrounding the clinical potential of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is tempered by the fact that key issues regarding their safety, efficacy, and long-term benefits have thus far been suboptimal. Small molecules can potentially relieve these problems at major junctions of stem cell biology and regenerative therapy. In this review, we will introduce recent advances in these important areas and the first-generation of small molecules used in the regenerative context. Current chemical biology studies will provide the archetype for future interdisciplinary collaborations, and improve clinical benefits of cell-based therapies. PMID:21513877

Major Management Challenges and Program Risks: Department of Transportation

DOT National Transportation Integrated Search

2001-01-01

This report is part of a special series entitled the Performance and Accountability Series: Major Management Challenges and Program Risks. This report addresses the major performance and accountability challenges facing the Department of Transportati...

Precision gas therapy using intelligent nanomedicine.

PubMed

He, Qianjun

2017-10-24

Gas therapy is an emerging and promising field, utilizing the unique therapeutic effects of several kinds of gases (NO, CO, H 2 S and H 2 ) towards many major diseases, including cancer and cardiovascular diseases, and it is also facing challenges relating to enhancing gas therapy efficacy and avoiding gas poisoning risks. Here, we have proposed a new concept for precision gas therapy using a nanomedicine strategy to overcome the challenges. In this perspective, we have addressed a series of existing and potential solutions from the point of view of nanomedicine, and conveyed a collection of opinions about future expandable research into precision gas therapy.

Asia on the move: research challenges for population geography.

PubMed

Hugo, G

1996-06-01

This paper "summarises some of the major changes which have occurred in international migration to, from, and within Asia in the last two decades....A number of theoretical challenges are put forward regarding the complex interrelationships between international population movements, economic development and social change. The employment of systems approaches, neoclassical economic theory, social networks and institutional approaches, and the potential role of population geography in developing a more comprehensive explanation of the changing dynamics of international migration in the region, are discussed. Also considered are the gender dimension in migration, remittance flows and their consequences, and policy issues." excerpt

Idiopathic burning mouth syndrome: a common treatment-refractory somatoform condition responsive to ECT.

PubMed

McGirr, Alexander; Davis, Lindsay; Vila-Rodriguez, Fidel

2014-04-30

Somatic symptom disorders are common causes of disability and suffering, and can pose significant management challenges. Idiopathic burning mouth syndrome is a challenging somatic symptom disorder with relatively high prevalence, particularly among post-menopausal women. Here, we present the case of a woman with severe treatment refractory idiopathic burning mouth syndrome and comorbid major depressive disorder, who was successfully treated with bitemporal electroconvulsive therapy. This case highlights the potential effectiveness of electroconvulsive therapy in idiopathic burning mouth syndrome when other treatment options have been exhausted. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Anti-infective use in children and pregnancy: current deficiencies and future challenges

PubMed Central

Gwee, Amanda; Cranswick, Noel

2015-01-01

There are a number of challenges to using anti-infective agents in children and pregnant women. There is limited understanding of the altered pharmacokinetics of anti-infectives in these populations and as a result, optimized dosing regimens are yet to be established. The potential adverse effects of the drug on pregnancy outcome and the developing foetus is a major consideration, and the long term implications of drug side effects must be taken into account when drug exposure occurs early in life. These factors hinder research and licensing of new anti-infective drugs in these populations. We describe the current deficiencies and future challenges of anti-infective use in children and pregnant women, providing specific examples. PMID:24588467

In situ fenestrations for the aortic arch and visceral segment: advances and challenges.

PubMed

Riga, Celia V; McWilliams, Richard G; Cheshire, Nicholas J W

2011-09-01

The management of complex aortic pathologies remains a major challenge particularly in the emergency setting. Bespoke fenestrated and branch stent graft technology has shown encouraging short- and mid-term results in selected patients. Despite tremendous technological advances in this field however, factors such as the inherent delay in device manufacturing, anatomical and technical challenges, high degree of planning, and cost hinder the wider applications of minimally invasive endovascular therapy. In situ fenestration of aortic stent grafts is an attractive alternative that eliminates the need for preoperative custom tailoring with the potential to widen the therapeutic options available and to offer a bailout option after inadvertent side branch occlusion. This article summarizes the principles of this technique and discusses its current applications.

Major Management Challenges and Program Risks. Department of State

DTIC Science & Technology

2001-01-01

Major Management Challenges and Program Risks Department of StateGAO-01-252 Form SF298 Citation Data Report Date ("DD MON YYYY") 00JAN2001 Report...Type N/A Dates Covered (from... to) ("DD MON YYYY") Title and Subtitle Major Management Challenges and Program Risks Department of State Contract or...special series, first issued in January 1999, entitled the Performance and Accountability Series: Major Management Challenges and Program Risks . In

Major Management Challenges and Program Risks. Department of the Interior

DTIC Science & Technology

2001-01-01

Major Management Challenges and Program Risks Department of the InteriorGAO-01-249 Report Date ("DD MON YYYY") 00JAN2001 Report Type N/A Dates...Covered (from... to) ("DD MON YYYY") Title and Subtitle Major Management Challenges and Program Risks Department of the Interior Contract or Grant...first issued in January 1999, entitled the Performance and Accountability Series: Major Management Challenges and Program Risks . In that series, GAO

Improving the clinical impact of biomaterials in cancer immunotherapy

PubMed Central

Gammon, Joshua M.; Dold, Neil M.; Jewell, Christopher M.

2016-01-01

Immunotherapies for cancer have progressed enormously over the past few decades, and hold great promise for the future. The successes of these therapies, with some patients showing durable and complete remission, demonstrate the power of harnessing the immune system to eradicate tumors. However, the effectiveness of current immunotherapies is limited by hurdles ranging from immunosuppressive strategies employed by tumors, to inadequate specificity of existing therapies, to heterogeneity of disease. Further, the vast majority of approved immunotherapies employ systemic delivery of immunomodulators or cells that make addressing some of these challenges more difficult. Natural and synthetic biomaterials–such as biocompatible polymers, self-assembled lipid particles, and implantable biodegradable devices–offer unique potential to address these hurdles by harnessing the benefits of therapeutic targeting, tissue engineering, co-delivery, controlled release, and sensing. However, despite the enormous investment in new materials and nanotechnology, translation of these ideas to the clinic is still an uncommon outcome. Here we review the major challenges facing immunotherapies and discuss how the newest biomaterials and nanotechnologies could help overcome these challenges to create new clinical options for patients. PMID:26871948

Supporting Greenhouse Gas Management Strategies with Observations and Analysis - Challenges and Opportunities

NASA Astrophysics Data System (ADS)

Butler, J. H.; Tarasova, O. A.

2014-12-01

Climate-change challenges facing society in the 21st century require an improved understanding of the global carbon-cycle and of the impacts and feedbacks of past, present, and future emissions of carbon-cycle gases. Global society faces a major challenge of reducing greenhouse gas emissions to virtually zero, most notably those of CO2, while at the same time facing variable and potentially overwhelming Earth System feedbacks. How it goes about this will depend upon the nature of impending international agreements, national laws, regional strategies, and social and economic forces. The challenge to those making observations to support, inform, or verify these reduction efforts, or to address potential Earth System feedbacks, lies in harmonizing a diverse array of observations and observing systems. Doing so is not trivial. Providing coherent, regional-scale information from these observations also requires improved modelling and ensemble reanalysis, but in the end such information must be relevant and reasonably certain. The challenge to us is to ensure a globally coherent observing and analysis system to supply the information that society will need to succeed. Policy-makers, scientists, government agencies, and businesses will need the best information available for decision-making and any observing and analysis system ultimately must be able to provide a coherent story over decades.

Major Management Challenges and Program Risks. Department of the Treasury

DTIC Science & Technology

2001-01-01

Major Management Challenges and Program Risks Department of the TreasuryGAO-01-254 Form SF298 Citation Data Report Date ("DD MON YYYY") 00JAN2001...Report Type N/A Dates Covered (from... to) ("DD MON YYYY") Title and Subtitle Major Management Challenges and Program Risks Department of the...High Risks (GAO-01-159SP), in November 2000.This report addresses the major performance and accountability challenges facing the Department of the

Transforming Global Health with Mobile Technologies and Social Enterprises

PubMed Central

Kayingo, Gerald

2012-01-01

More than 2,000 people convened for the ninth annual Global Health and Innovation Conference at Yale University on April 21-22, 2012. Participants discussed the latest innovations, ideas in development, lessons learned, opportunities and challenges in global health activities. Several themes emerged, including the important role of frontline workers, strengthening health systems, leveraging social media, and sustainable and impact-driven philanthropy. Overall, the major outcome of the conference was the increased awareness of the potential of mobile technologies and social enterprises in transforming global health. Experts warned that donations and technological advances alone will not transform global health unless there are strong functioning health infrastructures and improved workforce. It was noted that there is a critical need for an integrated systems approach to global health problems and a need for scaling up promising pilot projects. Lack of funding, accountability, and sustainability were identified as major challenges in global health. PMID:23012591

Automatic fall monitoring: a review.

PubMed

Pannurat, Natthapon; Thiemjarus, Surapa; Nantajeewarawat, Ekawit

2014-07-18

Falls and fall-related injuries are major incidents, especially for elderly people, which often mark the onset of major deterioration of health. More than one-third of home-dwelling people aged 65 or above and two-thirds of those in residential care fall once or more each year. Reliable fall detection, as well as prevention, is an important research topic for monitoring elderly living alone in residential or hospital units. The aim of this study is to review the existing fall detection systems and some of the key research challenges faced by the research community in this field. We categorize the existing platforms into two groups: wearable and ambient devices; the classification methods are divided into rule-based and machine learning techniques. The relative merit and potential drawbacks are discussed, and we also outline some of the outstanding research challenges that emerging new platforms need to address.

Automatic Fall Monitoring: A Review

PubMed Central

Pannurat, Natthapon; Thiemjarus, Surapa; Nantajeewarawat, Ekawit

2014-01-01

Falls and fall-related injuries are major incidents, especially for elderly people, which often mark the onset of major deterioration of health. More than one-third of home-dwelling people aged 65 or above and two-thirds of those in residential care fall once or more each year. Reliable fall detection, as well as prevention, is an important research topic for monitoring elderly living alone in residential or hospital units. The aim of this study is to review the existing fall detection systems and some of the key research challenges faced by the research community in this field. We categorize the existing platforms into two groups: wearable and ambient devices; the classification methods are divided into rule-based and machine learning techniques. The relative merit and potential drawbacks are discussed, and we also outline some of the outstanding research challenges that emerging new platforms need to address. PMID:25046016

Transforming global health with mobile technologies and social enterprises: global health and innovation conference.

PubMed

Kayingo, Gerald

2012-09-01

More than 2,000 people convened for the ninth annual Global Health and Innovation Conference at Yale University on April 21-22, 2012. Participants discussed the latest innovations, ideas in development, lessons learned, opportunities and challenges in global health activities. Several themes emerged, including the important role of frontline workers, strengthening health systems, leveraging social media, and sustainable and impact-driven philanthropy. Overall, the major outcome of the conference was the increased awareness of the potential of mobile technologies and social enterprises in transforming global health. Experts warned that donations and technological advances alone will not transform global health unless there are strong functioning health infrastructures and improved workforce. It was noted that there is a critical need for an integrated systems approach to global health problems and a need for scaling up promising pilot projects. Lack of funding, accountability, and sustainability were identified as major challenges in global health.

Western water and climate change

USGS Publications Warehouse

Dettinger, Michael; Udall, Bradley; Georgakakos, Aris P.

2015-01-01

In this context, four iconic river basins offer glimpses into specific challenges that climate change may bring to the West. The Colorado River is a system in which overuse and growing demands are projected to be even more challenging than climate-change-induced flow reductions. The Rio Grande offers the best example of how climate-change-induced flow declines might sink a major system into permanent drought. The Klamath is currently projected to face the more benign precipitation future, but fisheries and irrigation management may face dire straits due to warming air temperatures, rising irrigation demands, and warming waters in a basin already hobbled by tensions between endangered fisheries and agricultural demands. Finally, California's Bay-Delta system is a remarkably localized and severe weakness at the heart of the region's trillion-dollar economy. It is threatened by the full range of potential climate-change impacts expected across the West, along with major vulnerabilities to increased flooding and rising sea levels.

Trojan Horse Antibiotics—A Novel Way to Circumvent Gram-Negative Bacterial Resistance?

PubMed Central

Tillotson, Glenn S.

2016-01-01

Antibiotic resistance has been emerged as a major global health problem. In particular, gram-negative species pose a significant clinical challenge as bacteria develop or acquire more resistance mechanisms. Often, these bacteria possess multiple resistance mechanisms, thus nullifying most of the major classes of drugs. Novel approaches to this issue are urgently required. However, the challenges of developing new agents are immense. Introducing novel agents is fraught with hurdles, thus adapting known antibiotic classes by altering their chemical structure could be a way forward. A chemical addition to existing antibiotics known as a siderophore could be a solution to the gram-negative resistance issue. Siderophore molecules rely on the bacterial innate need for iron ions and thus can utilize a Trojan Horse approach to gain access to the bacterial cell. The current approaches to using this potential method are reviewed. PMID:27773991

Reuse of clinical data.

PubMed

Safran, C

2014-08-15

To provide an overview of the benefits of clinical data collected as a by-product of the care process, the potential problems with large aggregations of these data, the policy frameworks that have been formulated, and the major challenges in the coming years. This report summarizes some of the major observations from AMIA and IMIA conferences held on this admittedly broad topic from 2006 through 2013. This report also includes many unsupported opinions of the author. The benefits of aggregating larger and larger sets of routinely collected clinical data are well documented and of great societal benefit. These large data sets will probably never answer all possible clinical questions for methodological reasons. Non-traditional sources of health data that are patient-sources will pose new data science challenges. If we ever hope to have tools that can rapidly provide evidence for daily practice of medicine we need a science of health data perhaps modeled after the science of astronomy.

Trojan Horse Antibiotics-A Novel Way to Circumvent Gram-Negative Bacterial Resistance?

PubMed

Tillotson, Glenn S

2016-01-01

Antibiotic resistance has been emerged as a major global health problem. In particular, gram-negative species pose a significant clinical challenge as bacteria develop or acquire more resistance mechanisms. Often, these bacteria possess multiple resistance mechanisms, thus nullifying most of the major classes of drugs. Novel approaches to this issue are urgently required. However, the challenges of developing new agents are immense. Introducing novel agents is fraught with hurdles, thus adapting known antibiotic classes by altering their chemical structure could be a way forward. A chemical addition to existing antibiotics known as a siderophore could be a solution to the gram-negative resistance issue. Siderophore molecules rely on the bacterial innate need for iron ions and thus can utilize a Trojan Horse approach to gain access to the bacterial cell. The current approaches to using this potential method are reviewed.

Innovation & Collaboration Are Keys to Campus Water Management

ERIC Educational Resources Information Center

Thaler-Carter, Ruth E.

2013-01-01

Water, water everywhere--managing and conserving water resources is a major factor at campuses worldwide. Doing so is a challenge, since water is one of the most-used and ubiquitous resources in any environment. Water is often taken for granted and not measured by the people who use it the most, yet it might have the greatest potential for helping…

Adipose Tissue: Sanctuary for HIV/SIV Persistence and Replication.

PubMed

Pallikkuth, Suresh; Mohan, Mahesh

2015-12-01

This commentary highlights new findings from a recent study identifying adipose tissue as a potential HIV reservoir and a major site of inflammation during chronic human/simian immunodeficiency virus (HIV/SIV) infection. A concise discussion about upcoming challenges and new research avenues for reducing chronic adipose inflammation during HIV/SIV infection is presented. Copyright © 2015 Elsevier Ltd. All rights reserved.

Potential Teaching Model for Applying Novel Approaches of Renewed Estonian National Curriculum into Visual Art Classes in Primary School

ERIC Educational Resources Information Center

Vahter, Edna

2015-01-01

In 2010, the renewed national curriculum was legislated in Estonia. Major changes include a new list of cross-curricular topics, increased importance of integration and specification of the components of the art learning process. In this situation, the question arises--how to fully implement the challenges of the renewed curriculum in primary…

The Use of Quality Control and Data Mining Techniques for Monitoring Scaled Scores: An Overview. Research Report. ETS RR-12-20

ERIC Educational Resources Information Center

von Davier, Alina A.

2012-01-01

Maintaining comparability of test scores is a major challenge faced by testing programs that have almost continuous administrations. Among the potential problems are scale drift and rapid accumulation of errors. Many standard quality control techniques for testing programs, which can effectively detect and address scale drift for small numbers of…

Quality of Learning Outcomes in an Online Video-Based Learning Community: Potential and Challenges for Student Teachers

ERIC Educational Resources Information Center

So, Winnie Wing-mui

2012-01-01

This study investigates the learning outcomes of 25 student teachers in an online video-based learning community (VBLC). Data were drawn from the student teachers' written comments and feedback recorded in the VBLC and the post-course interviews. Based on Biggs and Collis's Structure of Observed Learning Outcomes (SOLO) taxonomy, the majority of…

The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety

PubMed Central

Ekor, Martins

2014-01-01

The use of herbal medicinal products and supplements has increased tremendously over the past three decades with not less than 80% of people worldwide relying on them for some part of primary healthcare. Although therapies involving these agents have shown promising potential with the efficacy of a good number of herbal products clearly established, many of them remain untested and their use are either poorly monitored or not even monitored at all. The consequence of this is an inadequate knowledge of their mode of action, potential adverse reactions, contraindications, and interactions with existing orthodox pharmaceuticals and functional foods to promote both safe and rational use of these agents. Since safety continues to be a major issue with the use of herbal remedies, it becomes imperative, therefore, that relevant regulatory authorities put in place appropriate measures to protect public health by ensuring that all herbal medicines are safe and of suitable quality. This review discusses toxicity-related issues and major safety concerns arising from the use of herbal medicinal products and also highlights some important challenges associated with effective monitoring of their safety. PMID:24454289

Challenges of climate change: omics-based biology of saffron plants and organic agricultural biotechnology for sustainable saffron production.

PubMed

Husaini, Amjad M

2014-01-01

Kashmir Valley is a major saffron (Crocus sativus Kashmirianus) growing area of the world, second only to Iran in terms of production. In Kashmir, saffron is grown on uplands (termed in the local language as "Karewas"), which are lacustrine deposits located at an altitude of 1585 to 1677 m above mean sea level (amsl), under temperate climatic conditions. Kashmir, despite being one of the oldest historical saffron-producing areas, faces a rapid decline of saffron industry. Among many other factors responsible for decline of saffron industry the preponderance of erratic rainfalls and drought-like situation have become major challenges imposed by climate change. Saffron has a limited coverage area as it is grown as a 'niche crop' and is a recognized "geographical indication," growing under a narrow microclimatic condition. As such it has become a victim of climate change effects, which has the potential of jeopardizing the livelihood of thousands of farmers and traders associated with it. The paper discusses the potential and actual impact of climate change process on saffron cultivation in Kashmir; and the biotechnological measures to address these issues.

Veno-venous ECMO: a synopsis of nine key potential challenges, considerations, and controversies

PubMed Central

2014-01-01

Background Following the 2009 H1N1 Influenza pandemic, extracorporeal membrane oxygenation (ECMO) emerged as a viable alternative in selected, severe cases of ARDS. Acute Respiratory Distress Syndrome (ARDS) is a major public health problem. Average medical costs for ARDS survivors on an annual basis are multiple times those dedicated to a healthy individual. Advances in medical and ventilatory management of severe lung injury and ARDS have improved outcomes in some patients, but these advances fail to consistently “rescue” a significant proportion of those affected. Discussion Here we present a synopsis of the challenges, considerations, and potential controversies regarding veno-venous ECMO that will be of benefit to anesthesiologists, surgeons, and intensivists, especially those newly confronted with care of the ECMO patient. We outline a number of points related to ECMO, particularly regarding cannulation, pump/oxygenator design, anticoagulation, and intravascular fluid management of patients. We then address these challenges/considerations/controversies in the context of their potential future implications on clinical approaches to ECMO patients, focusing on the development and advancement of standardized ECMO clinical practices. Summary Since the 2009 H1N1 pandemic ECMO has gained a wider acceptance. There are challenges that still must be overcome. Further investigations of the benefits and effects of ECMO need to be undertaken in order to facilitate the implementation of this technology on a larger scale. PMID:25110462

Targeting a global health problem: Vaccine design and challenges for the control of tick-borne diseases.

PubMed

de la Fuente, José; Contreras, Marinela; Estrada-Peña, Agustín; Cabezas-Cruz, Alejandro

2017-09-12

It has been over twenty years since the first vaccines for the control of tick infestations became commercially available. These vaccines proved their efficacy and the potential of this approach for the control of tick-borne diseases (TBDs), which represent a growing burden for human and animal health worldwide. In all these years, research in this area has produced new tick-derived and pathogen-derived candidate protective antigens. However, the potential of vaccines for the control of TBDs has been underestimated due to major challenges to reduce tick infestations, pathogen infection, multiplication and transmission, tick attachment and feeding time and/or host pathogen infection. Nevertheless, vaccines constitute the most safe and effective intervention for the control of TBDs in humans, domestic and wild animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fundamental transport mechanisms, fabrication and potential applications of nanoporous atomically thin membranes.

PubMed

Wang, Luda; Boutilier, Michael S H; Kidambi, Piran R; Jang, Doojoon; Hadjiconstantinou, Nicolas G; Karnik, Rohit

2017-06-06

Graphene and other two-dimensional materials offer a new approach to controlling mass transport at the nanoscale. These materials can sustain nanoscale pores in their rigid lattices and due to their minimum possible material thickness, high mechanical strength and chemical robustness, they could be used to address persistent challenges in membrane separations. Here we discuss theoretical and experimental developments in the emerging field of nanoporous atomically thin membranes, focusing on the fundamental mechanisms of gas- and liquid-phase transport, membrane fabrication techniques and advances towards practical application. We highlight potential functional characteristics of the membranes and discuss applications where they are expected to offer advantages. Finally, we outline the major scientific questions and technological challenges that need to be addressed to bridge the gap from theoretical simulations and proof-of-concept experiments to real-world applications.

Review of Potential Characterization Techniques in Approaching Energy and Sustainability

DOE PAGES

LePoire, David

2014-03-20

Societal prosperity is linked to sustainable energy and a healthy environment. But, tough global challenges include increased demand for fossil fuels, while approaching peak oil production and uncertainty in the environmental impacts of energy generation. Recently, energy use was identified as a major component of economic productivity, along with capital and labor. Furthermore, other environmental resources and impacts may be nearing environmental thresholds as indicated by nine planetary environmental boundaries, many of which are linked to energy production and use. Foresight techniques could be applied to guide future actions which include emphasis on (1) energy efficiency to bridge the transitionmore » to a renewable energy economy, (2) continued research, development, and assessment of new technologies, (3) improved understanding of environment impacts including natural capital use and degradation, (4) exploration of GDP alternative measures that include both economic production and environmental impacts, and (5) international cooperation and awareness of longer-term opportunities and their associated potential scenarios. Examples from the U.S. and the international community illustrate challenges and potential.« less

Vaccination of horses with a recombinant modified vaccinia Ankara virus (MVA) expressing African horse sickness (AHS) virus major capsid protein VP2 provides complete clinical protection against challenge.

PubMed

Alberca, Berta; Bachanek-Bankowska, Katarzyna; Cabana, Marta; Calvo-Pinilla, Eva; Viaplana, Elisenda; Frost, Lorraine; Gubbins, Simon; Urniza, Alicia; Mertens, Peter; Castillo-Olivares, Javier

2014-06-17

African horse sickness virus (AHSV) is an arthropod-borne pathogen that infects all species of equidae and causes high mortality in horses. Previously, a recombinant modified vaccinia Ankara (MVA) virus expressing the protein VP2 of AHSV serotype 4 was shown to induce virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR -/-) against virulent AHSV challenge. This study builds on the previous work, examining the protective efficacy of MVA-VP2 vaccination in the natural host of AHSV infection. A study group of 4 horses was vaccinated twice with a recombinant MVA virus expressing the major capsid protein (VP2) of AHSV serotype 9. Vaccinated animals and a control group of unvaccinated horses were then challenged with a virulent strain of AHSV-9. The vaccinated animals were completely protected against clinical disease and also against viraemia as measured by standard end-point dilution assays. In contrast, all control horses presented viraemia after challenge and succumbed to the infection. These results demonstrate the potential of recombinant MVA viruses expressing the outer capsid VP2 of AHSV as a protective vaccine against AHSV infection in the field. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Potential of poly(amidoamine) dendrimers as drug carriers of camptothecin based on encapsulation studies.

PubMed

Cheng, Yiyun; Li, Mingzhong; Xu, Tongwen

2008-08-01

Camptothecin (CPT), a plant alkaloid isolated from Camptotheca acuminata, has an extremely low solubility in aqueous medium, which presents a major challenge during drug formulation in clinical trails. In the present study we investigated the potential of poly(amidoamine) (PAMAM) dendrimers as drug carriers of CPT through aqueous solubility studies. Results showed that the aqueous solubility of CPT was significantly increased by PAMAM dendrimers. The effect of PAMAM generation on CPT solubility was also evaluated. These studies indicated that PAMAM dendrimers might be considered as biocompatible carriers of CPT.

Lignin conversion: Opportunities and challenges for the integrated biorefinery

DOE PAGES

Xie, Shangxian; Ragauskas, Arthur J.; Yuan, Joshua S.

2016-06-21

The utilization of lignin for fungible fuels and products represents one of the most imminent challenges in the modern biorefinery because most of the bioprocesses for lignocellulosic biofuels results in a lignin-containing waste stream. Considering lignin's abundance and relatively high energy content, this waste stream can be used as a feedstock for value-added products to improve the sustainability and economic feasibility of the biorefinery. Bioconversion of lignin with microbes recently emerged as an alternative lignin-valorization approach with significant potential. Typically, the microbial bioconversion of lignin requires three major steps: lignin depolymerization, aromatic compounds catabolism, and target product biosynthesis. In thismore » review, we summarize the most recent advances in lignin bioconversion to address the challenges in each of the three steps. In conclusion, we further discuss strategies and perspectives for future research to address the challenges in bioconversion of lignin.« less

Lignin conversion: Opportunities and challenges for the integrated biorefinery

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

Xie, Shangxian; Ragauskas, Arthur J.; Yuan, Joshua S.

The utilization of lignin for fungible fuels and products represents one of the most imminent challenges in the modern biorefinery because most of the bioprocesses for lignocellulosic biofuels results in a lignin-containing waste stream. Considering lignin's abundance and relatively high energy content, this waste stream can be used as a feedstock for value-added products to improve the sustainability and economic feasibility of the biorefinery. Bioconversion of lignin with microbes recently emerged as an alternative lignin-valorization approach with significant potential. Typically, the microbial bioconversion of lignin requires three major steps: lignin depolymerization, aromatic compounds catabolism, and target product biosynthesis. In thismore » review, we summarize the most recent advances in lignin bioconversion to address the challenges in each of the three steps. In conclusion, we further discuss strategies and perspectives for future research to address the challenges in bioconversion of lignin.« less

Advanced protein formulations

PubMed Central

Wang, Wei

2015-01-01

It is well recognized that protein product development is far more challenging than that for small-molecule drugs. The major challenges include inherent sensitivity to different types of stresses during the drug product manufacturing process, high rate of physical and chemical degradation during long-term storage, and enhanced aggregation and/or viscosity at high protein concentrations. In the past decade, many novel formulation concepts and technologies have been or are being developed to address these product development challenges for proteins. These concepts and technologies include use of uncommon/combination of formulation stabilizers, conjugation or fusion with potential stabilizers, site-specific mutagenesis, and preparation of nontraditional types of dosage forms—semiaqueous solutions, nonfreeze-dried solid formulations, suspensions, and other emerging concepts. No one technology appears to be mature, ideal, and/or adequate to address all the challenges. These gaps will likely remain in the foreseeable future and need significant efforts for ultimate resolution. PMID:25858529

Challenges facing early career academic cardiologists.

PubMed

Tong, Carl W; Ahmad, Tariq; Brittain, Evan L; Bunch, T Jared; Damp, Julie B; Dardas, Todd; Hijar, Amalea; Hill, Joseph A; Hilliard, Anthony A; Houser, Steven R; Jahangir, Eiman; Kates, Andrew M; Kim, Darlene; Lindman, Brian R; Ryan, John J; Rzeszut, Anne K; Sivaram, Chittur A; Valente, Anne Marie; Freeman, Andrew M

2014-06-03

Early career academic cardiologists currently face unprecedented challenges that threaten a highly valued career path. A team consisting of early career professionals and senior leadership members of American College of Cardiology completed this white paper to inform the cardiovascular medicine profession regarding the plight of early career cardiologists and to suggest possible solutions. This paper includes: 1) definition of categories of early career academic cardiologists; 2) general challenges to all categories and specific challenges to each category; 3) obstacles as identified by a survey of current early career members of the American College of Cardiology; 4) major reasons for the failure of physician-scientists to receive funding from National Institute of Health/National Heart Lung and Blood Institute career development grants; 5) potential solutions; and 6) a call to action with specific recommendations. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Medical entomology--back to the future?

PubMed

Reisen, William K

2014-12-01

Some of problems and challenges facing Medical/Veterinary Entomology are presented from my perspective, focusing on the current millennium. Topics include anthropogenic environmental changes created by population growth, administrative problems hindering science's response to these changes, and some of the scientific discoveries potentially providing solutions. As the title implies, many recent research discoveries have yet to be translated into major changes in control approaches for the major vectorborne public health problems, thereby providing an interesting mix of modern surveillance technology used to track problems and direct historical intervention solutions. Copyright © 2013 Elsevier B.V. All rights reserved.

Practical recommendations for the choice of anticoagulants in the management of patients with atrial fibrillation on ibrutinib.

PubMed

Chai, Khai Li; Rowan, Gail; Seymour, John F; Burbury, Kate; Carney, Dennis; Tam, Constantine S

2017-12-01

The management of AF represents a major challenge in patients with CLL, especially in elderly patients with multiple comorbidities who are representative of the majority of patients with CLL. This is especially complex in the case of ibrutinib. Many anticoagulants have potential for pharmacological interaction with ibrutinib, and ibrutinib itself has antiplatelet properties. Use of ibrutinib therapy in these patients mandates review and revision of the need for anticoagulation and best anticoagulant to use. Herein, we review the current knowledge of the metabolism of common anticoagulants and how they may interact with ibrutinib.

Recognition of medication information from discharge summaries using ensembles of classifiers.

PubMed

Doan, Son; Collier, Nigel; Xu, Hua; Pham, Hoang Duy; Tu, Minh Phuong

2012-05-07

Extraction of clinical information such as medications or problems from clinical text is an important task of clinical natural language processing (NLP). Rule-based methods are often used in clinical NLP systems because they are easy to adapt and customize. Recently, supervised machine learning methods have proven to be effective in clinical NLP as well. However, combining different classifiers to further improve the performance of clinical entity recognition systems has not been investigated extensively. Combining classifiers into an ensemble classifier presents both challenges and opportunities to improve performance in such NLP tasks. We investigated ensemble classifiers that used different voting strategies to combine outputs from three individual classifiers: a rule-based system, a support vector machine (SVM) based system, and a conditional random field (CRF) based system. Three voting methods were proposed and evaluated using the annotated data sets from the 2009 i2b2 NLP challenge: simple majority, local SVM-based voting, and local CRF-based voting. Evaluation on 268 manually annotated discharge summaries from the i2b2 challenge showed that the local CRF-based voting method achieved the best F-score of 90.84% (94.11% Precision, 87.81% Recall) for 10-fold cross-validation. We then compared our systems with the first-ranked system in the challenge by using the same training and test sets. Our system based on majority voting achieved a better F-score of 89.65% (93.91% Precision, 85.76% Recall) than the previously reported F-score of 89.19% (93.78% Precision, 85.03% Recall) by the first-ranked system in the challenge. Our experimental results using the 2009 i2b2 challenge datasets showed that ensemble classifiers that combine individual classifiers into a voting system could achieve better performance than a single classifier in recognizing medication information from clinical text. It suggests that simple strategies that can be easily implemented such as majority voting could have the potential to significantly improve clinical entity recognition.

Towards more accurate vegetation mortality predictions

DOE PAGES

Sevanto, Sanna Annika; Xu, Chonggang

2016-09-26

Predicting the fate of vegetation under changing climate is one of the major challenges of the climate modeling community. Here, terrestrial vegetation dominates the carbon and water cycles over land areas, and dramatic changes in vegetation cover resulting from stressful environmental conditions such as drought feed directly back to local and regional climate, potentially leading to a vicious cycle where vegetation recovery after a disturbance is delayed or impossible.

Antibody tumor penetration

PubMed Central

Thurber, Greg M.; Schmidt, Michael M.; Wittrup, K. Dane

2009-01-01

Antibodies have proven to be effective agents in cancer imaging and therapy. One of the major challenges still facing the field is the heterogeneous distribution of these agents in tumors when administered systemically. Large regions of untargeted cells can therefore escape therapy and potentially select for more resistant cells. We present here a summary of theoretical and experimental approaches to analyze and improve antibody penetration in tumor tissue. PMID:18541331

Young People's Health as a Challenge for Physical Education in Schools in the Twenty-First Century: The Case of Flanders (Belgium)

ERIC Educational Resources Information Center

Seghers, Jan; de Martelaer, Kristine; Cardon, Greet

2009-01-01

Background: A lack of physical activity (PA) and the occurrence of overweight and obesity among school-aged youth have become a major societal problem. Arising from the general concern about the future generations' health, schools have been found to be potentially important settings to promote positive health behaviour, since all pupils can be…

Nanotechnology: Opportunities and Challenges

NASA Technical Reports Server (NTRS)

Meyyappan, Meyya

2003-01-01

Nanotechnology seeks to exploit novel physical, chemical, biological, mechanical, electrical, and other properties, which arise primarily due to the nanoscale nature of certain materials. A key example is carbon nanotubes (CNTs) which exhibit unique electrical and extraordinary mechanical properties and offer remarkable potential for revolutionary applications in electronics devices, computing, and data storage technology, sensors, composites, nanoelectromechanical systems (NEMS), and as tip in scanning probe microscopy (SPM) for imaging and nanolithography. Thus the CNT synthesis, characterization, and applications touch upon all disciplines of science and engineering. This presentation will provide an overview and progress report on this and other major research candidates in Nanotechnology and address opportunities and challenges ahead.

Multi-channel probes to understand fission dynamics

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

Mosby, Shea Morgan

2016-04-15

Explaining the origin of the elements is a major outstanding question in nuclear astrophysics. Observed elemental abundance distribution shows strong nuclear physics effects. In conclusion, neutron-induced reactions are important for nuclear astrophysics and applied fields in nuclear energy and security. LANSCE has a program to address many of these questions directly with neutron beams on (near-)stable nuclei. Increasing demand for correlated data to test details of fission models poses additional challenges. Possibilities exist to extend existing experimental efforts to radioactive beam facilities. Kinematic focusing from using inverse kinematics has potential to circumvent some challenges associated with measuring correlations between fissionmore » output channels.« less

Light robotics: aiming towards all-optical nano-robotics

NASA Astrophysics Data System (ADS)

Glückstad, Jesper; Palima, Darwin; Banas, Andrew

2017-04-01

Light Robotics is a new field of research where ingredients from photonics, nanotechnology and biotechnology are put together in new ways to realize light-driven robotics at the smallest scales to solve major challenges primarily within the nanobio-domain but not limited hereto. Exploring the full potential of this new `drone-like' light-printed, light-driven, light-actuated micro- and nanorobotics in challenging geometries requires a versatile and real-time reconfigurable light addressing that can dynamically track a plurality of tiny tools in 3D to ensure real-time continuous light-delivery on the fly. Our latest developments in this new and exciting research area will be reviewed.

Concurrence of big data analytics and healthcare: A systematic review.

PubMed

Mehta, Nishita; Pandit, Anil

2018-06-01

The application of Big Data analytics in healthcare has immense potential for improving the quality of care, reducing waste and error, and reducing the cost of care. This systematic review of literature aims to determine the scope of Big Data analytics in healthcare including its applications and challenges in its adoption in healthcare. It also intends to identify the strategies to overcome the challenges. A systematic search of the articles was carried out on five major scientific databases: ScienceDirect, PubMed, Emerald, IEEE Xplore and Taylor & Francis. The articles on Big Data analytics in healthcare published in English language literature from January 2013 to January 2018 were considered. Descriptive articles and usability studies of Big Data analytics in healthcare and medicine were selected. Two reviewers independently extracted information on definitions of Big Data analytics; sources and applications of Big Data analytics in healthcare; challenges and strategies to overcome the challenges in healthcare. A total of 58 articles were selected as per the inclusion criteria and analyzed. The analyses of these articles found that: (1) researchers lack consensus about the operational definition of Big Data in healthcare; (2) Big Data in healthcare comes from the internal sources within the hospitals or clinics as well external sources including government, laboratories, pharma companies, data aggregators, medical journals etc.; (3) natural language processing (NLP) is most widely used Big Data analytical technique for healthcare and most of the processing tools used for analytics are based on Hadoop; (4) Big Data analytics finds its application for clinical decision support; optimization of clinical operations and reduction of cost of care (5) major challenge in adoption of Big Data analytics is non-availability of evidence of its practical benefits in healthcare. This review study unveils that there is a paucity of information on evidence of real-world use of Big Data analytics in healthcare. This is because, the usability studies have considered only qualitative approach which describes potential benefits but does not take into account the quantitative study. Also, majority of the studies were from developed countries which brings out the need for promotion of research on Healthcare Big Data analytics in developing countries. Copyright © 2018 Elsevier B.V. All rights reserved.

Pervasive mobile healthcare systems for chronic disease monitoring.

PubMed

Huzooree, Geshwaree; Kumar Khedo, Kavi; Joonas, Noorjehan

2017-05-01

Pervasive mobile healthcare system has the potential to improve healthcare and the quality of life of chronic disease patients through continuous monitoring. Recently, many articles related to pervasive mobile healthcare system focusing on health monitoring using wireless technologies have been published. The main aim of this review is to evaluate the state-of-the-art pervasive mobile healthcare systems to identify major technical requirements and design challenges associated with the realization of a pervasive mobile healthcare system. A systematic literature review was conducted over IEEE Xplore Digital Library to evaluate 20 pervasive mobile healthcare systems out of 683 articles from 2011 to 2016. The classification of the pervasive mobile healthcare systems and other important factors are discussed. Potential opportunities and challenges are pointed out for the further deployment of effective pervasive mobile healthcare systems. This article helps researchers in health informatics to have a holistic view toward understanding pervasive mobile healthcare systems and points out new technological trends and design challenges that researchers have to consider when designing such systems for better adoption, usability, and seamless integration.

Heutagogy: An alternative practice based learning approach.

PubMed

Bhoyrub, John; Hurley, John; Neilson, Gavin R; Ramsay, Mike; Smith, Margaret

2010-11-01

Education has explored and utilised multiple approaches in attempts to enhance the learning and teaching opportunities available to adult learners. Traditional pedagogy has been both directly and indirectly affected by andragogy and transformational learning, consequently widening our understandings and approaches toward view teaching and learning. Within the context of nurse education, a major challenge has been to effectively apply these educational approaches to the complex, unpredictable and challenging environment of practice based learning. While not offered as a panacea to such challenges, heutagogy is offered in this discussion paper as an emerging and potentially highly congruent educational framework to place around practice based learning. Being an emergent theory its known conceptual underpinnings and possible applications to nurse education need to be explored and theoretically applied. Through placing the adult learner at the foreground of grasping learning opportunities as they unpredictability emerge from a sometimes chaotic environment, heutagogy can be argued as offering the potential to minimise many of the well published difficulties of coordinating practice with faculty teaching and learning. Copyright © 2010 Elsevier Ltd. All rights reserved.

Re-assessing the relationship between sporozoite dose and incubation period in Plasmodium vivax malaria: a systematic re-analysis.

PubMed

Lover, Andrew A; Coker, Richard J

2014-05-01

Infections with the malaria parasite Plasmodium vivax are noteworthy for potentially very long incubation periods (6-9 months), which present a major barrier to disease elimination. Increased sporozoite challenge has been reported to be associated with both shorter incubation and pre-patent periods in a range of human challenge studies. However, this evidence base has scant empirical foundation, as these historical analyses were limited by available analytic methods, and provides no quantitative estimates of effect size. Following a comprehensive literature search, we re-analysed all identified studies using survival and/or logistic models plus contingency tables. We have found very weak evidence for dose-dependence at entomologically plausible inocula levels. These results strongly suggest that sporozoite dosage is not an important driver of long-latency. Evidence presented suggests that parasite strain and vector species have quantitatively greater impacts, and the potential existence of a dose threshold for human dose-response to sporozoites. Greater consideration of the complex interplay between these aspects of vectors and parasites are important for human challenge experiments, vaccine trials, and epidemiology towards global malaria elimination.

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

Rittmann, Bruce; Krajmalnik‐Brown, Rosa; Zevin, Alexander

The grandest challenge facing human society today is providing large amounts of energy and industrial chemicals that are renewable and carbon-neutral. An outstanding opportunity lies in employing photosynthetic microorganisms, which have the potential to generate energy and chemical feedstock from sunlight and CO 2 at rates 10 to 100 times greater than plants. Major challenges for solar-powered production using photosynthetic microorganisms are associated with the harvesting and downstream processing of biomass to yield the usable energy or material feedstock e.g. The technical challenges and costs of downstream processing could be avoided if, powered by solar energy, the photosynthetic microorganisms weremore » to convert CO 2 directly to the desired product, which they release for direct harvesting. This approach creates a true photosynthetic factory, our goal for Photosynthetic Factory Direct! Our team is able to genetically modify the cyanobacterium Synechocystis sp. PCC 6803 so that it produces and excretes a range of renewable energy and chemical products directly from CO 2 and sunlight. Essential to realizing the potential of the photosynthetic factory is an engineered Advanced Photobioreactor (APBR) for reliable synthesis and harvest of the products.« less

Technological intimacy in haemodialysis nursing.

PubMed

Bennett, Paul N

2011-09-01

BENNETT PN. Nursing Inquiry 2011; 18: 247-252 Technological intimacy in haemodialysis nursing Technology plays a major role in nursing care. Among the challenges for nurses is being able to maintain a patient focus while surrounded by highly complex technology. The provision of high quality nursing care in technologically complex environments is particularly challenging when nurses develop relationships with their patients over an extended period of time. In these environments the potential for intimate relationships can increase. This potential for intimacy is evident in the haemodialysis context where dialysis technology, nurses and patients interface. As nurses and patients can spend up to 20 hours per week together intimate relationships can develop. This paper identifies the challenges these dialysis nurses face and introduces the concept of technological intimacy. Technological intimacy can be defined as physical touching and self disclosure, associated with closeness and knowing, that is undertaken in the full view of others in a healthcare environment dominated by technology. In the haemodialysis context technological intimacy has been scarcely acknowledged and rarely researched. Further research will assist in guiding haemodialysis nursing practice. © 2011 Blackwell Publishing Ltd.

Fungal Enzymes for Bio-Products from Sustainable and Waste Biomass.

PubMed

Gupta, Vijai K; Kubicek, Christian P; Berrin, Jean-Guy; Wilson, David W; Couturier, Marie; Berlin, Alex; Filho, Edivaldo X F; Ezeji, Thaddeus

2016-07-01

Lignocellulose, the most abundant renewable carbon source on earth, is the logical candidate to replace fossil carbon as the major biofuel raw material. Nevertheless, the technologies needed to convert lignocellulose into soluble products that can then be utilized by the chemical or fuel industries face several challenges. Enzymatic hydrolysis is of major importance, and we review the progress made in fungal enzyme technology over the past few years with major emphasis on (i) the enzymes needed for the conversion of polysaccharides (cellulose and hemicellulose) into soluble products, (ii) the potential uses of lignin degradation products, and (iii) current progress and bottlenecks for the use of the soluble lignocellulose derivatives in emerging biorefineries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of vaccines for bio-warfare agents.

PubMed

Rosenthal, S R; Clifford, J C M

2002-01-01

There is a recognized need for the development of new vaccines (as well as other biologicals and drugs) to counteract the effects of a potential bio-terrorist or bio-warfare event in the U.S. domestic population and military forces. Regulation of products to protect against potential bio-warfare agents poses unique challenges since the usual measures of efficacy that require exposure to natural disease may not currently be possible, for epidemiological and ethical reasons. To help to address this issue, the FDA has published and requested comments on a proposed animal rule intended to address certain efficacy issues for new agents for use against lethal or permanently disabling toxic substances. Recent product development activity has focused on Bacillus anthracis (anthrax) and variola major (smallpox), agents that are regarded as highest priority in posing a risk to national security. FDA resources exist to assist vaccine developers with regard to the novel challenges posed in the dinical development of these products.

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

Cheng, Shiwang; Xie, Shi-Jie; Carrillo, Jan-Michael Y.

Polymer nanocomposites (PNCs) are important materials that are widely used in many current technologies and potentially have broader applications in the future due to their excellent property of tunability, light weight and low cost. But, expanding the limits in property enhancement remains a fundamental scientific challenge. We demonstrate that well-dispersed, small (diameter ~1.8 nm) nanoparticles with attractive interactions lead to unexpectedly large and qualitatively new changes in PNC structural dynamics in comparison to conventional composites based on particles of diameter ~10-50 nm. At the same time, the zero-shear viscosity at high temperatures remains comparable to that of the neat polymer,more » thereby retaining good processibility and resolving a major challenge in PNC applications. These results suggest that the nanoparticle mobility and relatively short lifetimes of nanoparticlepolymer associations open qualitatively new horizons in tunability of macroscopic properties in nanocomposites with high potential for the development of new functional materials.« less

Microbial synthesis gas utilization and ways to resolve kinetic and mass-transfer limitations.

PubMed

Yasin, Muhammad; Jeong, Yeseul; Park, Shinyoung; Jeong, Jiyeong; Lee, Eun Yeol; Lovitt, Robert W; Kim, Byung Hong; Lee, Jinwon; Chang, In Seop

2015-02-01

Microbial conversion of syngas to energy-dense biofuels and valuable chemicals is a potential technology for the efficient utilization of fossils (e.g., coal) and renewable resources (e.g., lignocellulosic biomass) in an environmentally friendly manner. However, gas-liquid mass transfer and kinetic limitations are still major constraints that limit the widespread adoption and successful commercialization of the technology. This review paper provides rationales for syngas bioconversion and summarizes the reaction limited conditions along with the possible strategies to overcome these challenges. Mass transfer and economic performances of various reactor configurations are compared, and an ideal case for optimum bioreactor operation is presented. Overall, the challenges with the bioprocessing steps are highlighted, and potential solutions are suggested. Future research directions are provided and a conceptual design for a membrane-based syngas biorefinery is proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quantum-Dot-Based Solar Cells: Recent Advances, Strategies, and Challenges.

PubMed

Kim, Mee Rahn; Ma, Dongling

2015-01-02

Among next-generation photovoltaic systems requiring low cost and high efficiency, quantum dot (QD)-based solar cells stand out as a very promising candidate because of the unique and versatile characteristics of QDs. The past decade has already seen rapid conceptual and technological advances on various aspects of QD solar cells, and diverse opportunities, which QDs can offer, predict that there is still ample room for further development and breakthroughs. In this Perspective, we first review the attractive advantages of QDs, such as size-tunable band gaps and multiple exciton generation (MEG), beneficial to solar cell applications. We then analyze major strategies, which have been extensively explored and have largely contributed to the most recent and significant achievements in QD solar cells. Finally, their high potential and challenges are discussed. In particular, QD solar cells are considered to hold immense potential to overcome the theoretical efficiency limit of 31% for single-junction cells.

Affordances and Alignments: Continuing Challenges in Advising Undergraduate Psychology Majors

ERIC Educational Resources Information Center

Landrum, R. Eric

2018-01-01

Challenges abound in providing accurate and useful information to prospective and declared psychology majors about their career options and how to make decisions that will lead to satisfying and rewarding postgraduate lives. One component of this challenge is that by majoring in psychology, career affordances (i.e., the opportunities and…

Western water and climate change.

PubMed

Dettinger, Michael; Udall, Bradley; Georgakakos, Aris

2015-12-01

The western United States is a region long defined by water challenges. Climate change adds to those historical challenges, but does not, for the most part, introduce entirely new challenges; rather climate change is likely to stress water supplies and resources already in many cases stretched to, or beyond, natural limits. Projections are for continued and, likely, increased warming trends across the region, with a near certainty of continuing changes in seasonality of snowmelt and streamflows, and a strong potential for attendant increases in evaporative demands. Projections of future precipitation are less conclusive, although likely the northern-most West will see precipitation increases while the southernmost West sees declines. However, most of the region lies in a broad area where some climate models project precipitation increases while others project declines, so that only increases in precipitation uncertainties can be projected with any confidence. Changes in annual and seasonal hydrographs are likely to challenge water managers, users, and attempts to protect or restore environmental flows, even where annual volumes change little. Other impacts from climate change (e.g., floods and water-quality changes) are poorly understood and will likely be location dependent. In this context, four iconic river basins offer glimpses into specific challenges that climate change may bring to the West. The Colorado River is a system in which overuse and growing demands are projected to be even more challenging than climate-change-induced flow reductions. The Rio Grande offers the best example of how climate-change-induced flow declines might sink a major system into permanent drought. The Klamath is currently projected to face the more benign precipitation future, but fisheries and irrigation management may face dire straits due to warming air temperatures, rising irrigation demands, and warming waters in a basin already hobbled by tensions between endangered fisheries and agricultural demands. Finally, California's Bay-Delta system is a remarkably localized and severe weakness at the heart of the region's trillion-dollar economy. It is threatened by the full range of potential climate-change impacts expected across the West, along with major vulnerabilities to increased flooding and rising sea levels.

The physical challenges of early breastfeeding.

PubMed

Kelleher, Christa M

2006-11-01

Breastfeeding rates have recently increased in the United States and Canada and a majority of women now initiate breastfeeding. Feminist scholarship on breastfeeding has addressed a variety of issues related to women's breastfeeding experiences but has tended to ignore or downplay the potentially physically challenging aspects of early breastfeeding. This study, based on semi-structured, in-depth interviews with 52 women from Canada and the United States conducted at approximately one month postpartum, examines women's experiences of pain and discomfort associated with breastfeeding. The findings demonstrate that many women experienced pain and discomfort and that they were generally surprised by the extent, intensity and duration of discomfort and pain, which ranged from mild to severe. Several women indicated that the physical impact of breastfeeding affected their relationship with their baby; others indicated that they became hesitant to continue the practice due to feelings of physical vulnerability, pain and/or discomfort. Lastly, women's experiences of the physical implications of breastfeeding were influenced in part by assistance provided by health care practitioners, in both positive and negative ways. The practice of breastfeeding has the potential to challenge women's physicality. Feminist scholars addressing the topic of breastfeeding, women's postpartum health, and embodiment must more directly and comprehensively account for the potentially negative physical implications and demands associated with early breastfeeding.

Challenges faced by multidisplinary new investigators on addressing grand challenges in global health

PubMed Central

2014-01-01

Background The grand challenges approach aims to spark innovative and transformative strategies to overcome barriers to significant global health issues. Grand Challenges Canada endorses an ‘Integrated Innovation™’ approach that focuses on the intersection of scientific/technological, social and business innovation. In this article we explore themes emerging from a dialogue between the authors, who are multidisciplinary recipients of the ‘Rising Stars in Global Health’ award from Grand Challenges Canada, regarding benefits of engaging in integrated innovation research, and recommendations for how this approach may develop in the future. Discussion Our dialogue followed a semi-structured interview format that addressed three topics: 1) reflections on applying an Integrated Innovation™ approach for global health; 2) thoughts on participation in the Grand Challenges 2012 meeting; and 3) authors’ visions of Grand Challenges Canada and the Grand Challenge movement towards 2020. The dialogue was transcribed verbatim and we used thematic analysis techniques to identify, analyze and report themes in the data. Benefits of working using the Grand Challenges approach centered on two themes: a) the potential for scientific breakthrough and b) building interdisciplinary collaborations and a community of scholars. Challenges and opportunities for Grand Challenges in moving forward included: a) capacity building, particularly regarding Integrated Innovation™ and scale-up planning; b) interdisciplinary and international mentorship for new investigators; and c) potential for future commercialization. Conclusions Our discussion highlighted that Integrated Innovation™ offers the opportunity to develop new theories, methods and approaches to global health while simultaneously fostering a collaborative spirit grounded in international, interdisciplinary collaborations. However, the arguable over-emphasis on corporatization poses a major challenge for new investigators. We propose a more balanced way forward that can harness technology to foster mentorship across time and space to support the development of such skills and ideas among new investigators. PMID:24735677

Learning from Trending, Precursor Analysis, and System Failures

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

Youngblood, R. W.; Duffey, R. B.

2015-11-01

Models of reliability growth relate current system unreliability to currently accumulated experience. But “experience” comes in different forms. Looking back after a major accident, one is sometimes able to identify previous events or measurable performance trends that were, in some sense, signaling the potential for that major accident: potential that could have been recognized and acted upon, but was not recognized until the accident occurred. This could be a previously unrecognized cause of accidents, or underestimation of the likelihood that a recognized potential cause would actually operate. Despite improvements in the state of practice of modeling of risk and reliability,more » operational experience still has a great deal to teach us, and work has been going on in several industries to try to do a better job of learning from experience before major accidents occur. It is not enough to say that we should review operating experience; there is too much “experience” for such general advice to be considered practical. The paper discusses the following: 1. The challenge of deciding what to focus on in analysis of operating experience. 2. Comparing what different models of learning and reliability growth imply about trending and precursor analysis.« less

Using natural products for drug discovery: the impact of the genomics era.

PubMed

Zhang, Mingzi M; Qiao, Yuan; Ang, Ee Lui; Zhao, Huimin

2017-05-01

Evolutionarily selected over billions of years for their interactions with biomolecules, natural products have been and continue to be a major source of pharmaceuticals. In the 1990s, pharmaceutical companies scaled down their natural product discovery programs in favor of synthetic chemical libraries due to major challenges such as high rediscovery rates, challenging isolation, and low production titers. Propelled by advances in DNA sequencing and synthetic biology technologies, insights into microbial secondary metabolism provided have inspired a number of strategies to address these challenges. Areas covered: This review highlights the importance of genomics and metagenomics in natural product discovery, and provides an overview of the technical and conceptual advances that offer unprecedented access to molecules encoded by biosynthetic gene clusters. Expert opinion: Genomics and metagenomics revealed nature's remarkable biosynthetic potential and her vast chemical inventory that we can now prioritize and systematically mine for novel chemical scaffolds with desirable bioactivities. Coupled with synthetic biology and genome engineering technologies, significant progress has been made in identifying and predicting the chemical output of biosynthetic gene clusters, as well as in optimizing cluster expression in native and heterologous host systems for the production of pharmaceutically relevant metabolites and their derivatives.

Using natural products for drug discovery: the impact of the genomics era

PubMed Central

Zhang, Mingzi M; Qiao, Yuan; Ang, Ee Lui; Zhao, Huimin

2017-01-01

Introduction Evolutionarily selected over billions of years for their interactions with biomolecules, natural products have been and continue to be a major source of pharmaceuticals. In the 1990s, pharmaceutical companies scaled down their natural product discovery programs in favor of synthetic chemical libraries due to major challenges such as high rediscovery rates, challenging isolation, and low production titers. Propelled by advances in DNA sequencing and synthetic biology technologies, insights into microbial secondary metabolism provided have inspired a number of strategies to address these challenges. Areas covered This review highlights the importance of genomics and metagenomics in natural product discovery, and provides an overview of the technical and conceptual advances that offer unprecedented access to molecules encoded by biosynthetic gene clusters. Expert opinion Genomics and metagenomics revealed nature’s remarkable biosynthetic potential and her vast chemical inventory that we can now prioritize and systematically mine for novel chemical scaffolds with desirable bioactivities. Coupled with synthetic biology and genome engineering technologies, significant progress has been made in identifying and predicting the chemical output of biosynthetic gene clusters, as well as in optimizing cluster expression in native and heterologous host systems for the production of pharmaceutically relevant metabolites and their derivatives. PMID:28277838

Applied aerodynamics: Challenges and expectations

NASA Technical Reports Server (NTRS)

Peterson, Victor L.; Smith, Charles A.

1993-01-01

Aerospace is the leading positive contributor to this country's balance of trade, derived largely from the sale of U.S. commercial aircraft around the world. This powerfully favorable economic situation is being threatened in two ways: (1) the U.S. portion of the commercial transport market is decreasing, even though the worldwide market is projected to increase substantially; and (2) expenditures are decreasing for military aircraft, which often serve as proving grounds for advanced aircraft technology. To retain a major share of the world market for commercial aircraft and continue to provide military aircraft with unsurpassed performance, the U.S. aerospace industry faces many technological challenges. The field of applied aerodynamics is necessarily a major contributor to efforts aimed at meeting these technological challenges. A number of emerging research results that will provide new opportunities for applied aerodynamicists are discussed. Some of these have great potential for maintaining the high value of contributions from applied aerodynamics in the relatively near future. Over time, however, the value of these contributions will diminish greatly unless substantial investments continue to be made in basic and applied research efforts. The focus: to increase understanding of fluid dynamic phenomena, identify new aerodynamic concepts, and provide validated advanced technology for future aircraft.

Pandemic policy and planning considerations for universities: findings from a tabletop exercise.

PubMed

Beaton, Randal; Stergachis, Andy; Thompson, Jack; Osaki, Carl; Johnson, Clark; Charvat, Steven J; Marsden-Haug, Nicola

2007-12-01

The potential for a novel influenza virus to cause a pandemic represents a significant threat to global health. Planning for pandemic flu, as compared to planning for other types of hazards, presents some unique challenges to businesses, communities, and education institutions. To identify and address the challenges that may be faced by major metropolitan universities during a flu pandemic, a tabletop exercise was developed, offered, and evaluated. Its purpose was to assess existing University of Washington (UW) plans and policies for responding to an influenza pandemic. On May 31, 2006, more than 50 participants, including UW administrators and unit leaders and a number of key external partners, participated in a tabletop exercise designed to simulate all phases of an influenza pandemic. This exercise revealed existing gaps in university pandemic influenza plans and policies, including issues related to isolation and quarantine, continuity of operations, disaster mental health services, integration of volunteers into a disaster response, tracking travel of university students and personnel, communication problems, and ways to meet the needs of resident and foreign students and faculty during an outbreak. Policy and planning recommendations are offered that address each of these challenges faced by UW as well as other major research universities and colleges.

Challenges and opportunities associated with waste management in India

PubMed Central

Kumar, Sunil; Smith, Stephen R.; Fowler, Geoff; Velis, Costas; Kumar, S. Jyoti; Arya, Shashi; Rena; Kumar, Rakesh

2017-01-01

India faces major environmental challenges associated with waste generation and inadequate waste collection, transport, treatment and disposal. Current systems in India cannot cope with the volumes of waste generated by an increasing urban population, and this impacts on the environment and public health. The challenges and barriers are significant, but so are the opportunities. This paper reports on an international seminar on ‘Sustainable solid waste management for cities: opportunities in South Asian Association for Regional Cooperation (SAARC) countries’ organized by the Council of Scientific and Industrial Research-National Environmental Engineering Research Institute and the Royal Society. A priority is to move from reliance on waste dumps that offer no environmental protection, to waste management systems that retain useful resources within the economy. Waste segregation at source and use of specialized waste processing facilities to separate recyclable materials has a key role. Disposal of residual waste after extraction of material resources needs engineered landfill sites and/or investment in waste-to-energy facilities. The potential for energy generation from landfill via methane extraction or thermal treatment is a major opportunity, but a key barrier is the shortage of qualified engineers and environmental professionals with the experience to deliver improved waste management systems in India. PMID:28405362

Risks of nutrigenomics and nutrigenetics? What the scientists say.

PubMed

Hurlimann, T; Menuz, V; Graham, J; Robitaille, J; Vohl, M-C; Godard, B

2014-01-01

Nutrigenomics and nutrigenetics (hereafter NGx) have stimulated expectations for beneficial applications in public health and individuals. Yet, the potential achievability of such promise is not without socioethical considerations that challenge NGx implementation. This paper focuses on the opinions of NGx researchers about potential risks raised by NGx. The results of an online survey show that these researchers (n = 126) are fairly confident about the potential benefits of NGx, and that most downplay its potential risks. Researchers in this field do not believe that NGx will reconfigure foods as medication or transform the conception of eating into a health hazard. The majority think that NGx will produce no added burden on individuals to get tested or to remain compliant with NGx recommendations, nor that NGx will threaten individual autonomy in daily food choice. The majority of researchers do not think that NGx will lead to discrimination against and/or stigmatization of people who do not comply with NGx dietary recommendations. Despite this optimism among NGx researchers, we suggest that key risk factors raised by the socioethical context in which NGx applications will be implemented need to be considered.

World Spatiotemporal Analytics and Mapping Project (WSTAMP): Discovering, Exploring, and Mapping Spatiotemporal Patterns across the World s Largest Open Source Geographic Data Sets

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

Stewart, Robert N; Piburn, Jesse O; Sorokine, Alexandre

The application of spatiotemporal (ST) analytics to integrated data from major sources such as the World Bank, United Nations, and dozens of others holds tremendous potential for shedding new light on the evolution of cultural, health, economic, and geopolitical landscapes on a global level. Realizing this potential first requires an ST data model that addresses challenges in properly merging data from multiple authors, with evolving ontological perspectives, semantical differences, and changing attributes, as well as content that is textual, numeric, categorical, and hierarchical. Equally challenging is the development of analytical and visualization approaches that provide a serious exploration of thismore » integrated data while remaining accessible to practitioners with varied backgrounds. The WSTAMP project at Oak Ridge National Laboratory has yielded two major results in addressing these challenges: 1) development of the WSTAMP database, a significant advance in ST data modeling that integrates 10,000+ attributes covering over 200 nation states spanning over 50 years from over 30 major sources and 2) a novel online ST exploratory and analysis tool providing an array of modern statistical and visualization techniques for analyzing these data temporally, spatially, and spatiotemporally under a standard analytic workflow. We discuss the status of this work and report on major findings. Acknowledgment Prepared by Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, Tennessee 37831-6285, managed by UT-Battelle, LLC for the U. S. Department of Energy under contract no. DEAC05-00OR22725. Copyright This manuscript has been authored by employees of UT-Battelle, LLC, under contract DE-AC05-00OR22725 with the U.S. Department of Energy. Accordingly, the United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes.« less

Major Management Challenges and Program Risks. Department of Labor

DTIC Science & Technology

2001-01-01

Major Management Challenges and Program Risks Department of LaborGAO-01-251 Form SF298 Citation Data Report Date ("DD MON YYYY") 00JAN2001 Report...Type N/A Dates Covered (from... to) ("DD MON YYYY") Title and Subtitle Major Management Challenges and Program Risks Department of Labor Contract or... Challenges and High Risks (GAO-01-159SP), in November 2000. This 2001 Performance and Accountability Series contains separate reports on 21 agencies

A means of improving public health in low- and middle-income countries? Benefits and challenges of international public-private partnerships.

PubMed

Kostyak, L; Shaw, D M; Elger, B; Annaheim, B

2017-08-01

In the last two decades international public-private partnerships have become increasingly important to improving public health in low- and middle-income countries. Governments realize that involving the private sector in projects for financing, innovation, development, and distribution can make a valuable contribution to overcoming major health challenges. Private-public partnerships for health can generate numerous benefits but may also raise some concerns. To guide best practice for public-private partnerships for health to maximize benefits and minimize risks, the first step is to identify potential benefits, challenges, and motives. We define motives as the reasons why private partners enter partnerships with a public partner. We conducted a systematic review of the literature using the PRISMA guidelines. We reviewed the literature on the benefits and challenges of public-private partnerships for health in low- and middle-income countries provided by international pharmaceutical companies and other health-related companies. We provide a description of these benefits, challenges, as well as of motives of private partners to join partnerships. An approach of systematic categorization was used to conduct this research. We identified six potential benefits, seven challenges, and three motives. Our main finding was a significant gap in the available academic literature on this subject. Further empirical research using both qualitative and quantitative approaches is required. From the limited information that is readily available, we conclude that public-private partnerships for health imply several benefits but with some noticeable and crucial limitations. In this article, we provide a description of these benefits and challenges, discuss key themes, and conclude that empirical research is required to determine the full extent of the challenges addressed in the literature. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Potential Alternatives to Classical Biocontrol: Using Native Agents in Invaded Habitats and Genetically Engineered Sterile Cultivars for Invasive Plant Management

Treesearch

ShiLi Miao; Yi Li; Qinfeng Guo; Hua Yu; JiangQing Ding; et al.

2012-01-01

The development of an effective approach to control and eradication of invasive species has become a major challenge to scientists, managers, and society. Biocontrol has been widely utilized to control exotic plants in the past few decades with some degree of sucess. However, there have been an increasing number of controversies pertaining to this approach, largely...

Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance.

PubMed

Thurber, Greg M; Schmidt, Michael M; Wittrup, K Dane

2008-09-01

Antibodies have proven to be effective agents in cancer imaging and therapy. One of the major challenges still facing the field is the heterogeneous distribution of these agents in tumors when administered systemically. Large regions of untargeted cells can therefore escape therapy and potentially select for more resistant cells. We present here a summary of theoretical and experimental approaches to analyze and improve antibody penetration in tumor tissue.

Smart wormlike micelles.

PubMed

Chu, Zonglin; Dreiss, Cécile A; Feng, Yujun

2013-09-07

A major scientific challenge of the past decade pertaining to the field of soft matter has been to craft 'adaptable' materials, inspired by nature, which can dynamically alter their structure and functionality on demand, in response to triggers produced by environmental changes. Amongst these, 'smart' surfactant wormlike micelles, responsive to external stimuli, are a particularly recent area of development, yet highly promising, given the versatility of the materials but simplicity of the design-relying on small amphiphilic molecules and their spontaneous self-assembly. The switching 'on' and 'off' of the micellar assembly structures has been reported using electrical, optical, thermal or pH triggers and is now envisaged for multiple stimuli. The structural changes, in turn, can induce major variations in the macroscopic characteristics, affecting properties such as viscosity and elasticity and sometimes even leading to a spontaneous and effective 'sol-gel' transition. These original smart materials based on wormlike micelles have been successfully used in the oil industry, and offer a significant potential in a wide range of other technological applications, including biomedicine, cleaning processes, drag reduction, template synthesis, to name but a few. This review will report results in this field published over the last few years, describe the potential and practical applications of stimuli-responsive wormlike micelles and point out future challenges.

Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

PubMed

Barruet, Emilie; Hsiao, Edward C

2016-01-01

Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

IRMPD Spectroscopy Sheds New (Infrared) Light on the Sulfate Pattern of Carbohydrates.

PubMed

Schindler, B; Barnes, L; Gray, C J; Chambert, S; Flitsch, S L; Oomens, J; Daniel, R; Allouche, A R; Compagnon, I

2017-03-16

IR spectroscopy of gas-phase ions is proposed to resolve positional isomers of sulfated carbohydrates. Mass spectrometric fingerprints and gas-phase vibrational spectra in the near and mid-IR regions were obtained for sulfated monosaccharides, yielding unambiguous signatures of sulfated isomers. We report the first systematic exploration of the biologically relevant but notoriously challenging deprotonated state in the near IR region. Remarkably, anions displayed very atypical vibrational profiles, which challenge the well-established DFT (Density Functionnal Theory) modeling. The proposed approach was used to elucidate the sulfate patterns in glycosaminoglycans, a ubiquitous class of mammalian carbohydrates, which is regarded as a major challenge in carbohydrate structural analysis. Isomeric glycosaminoglycan disaccharides from heparin and chondroitin sources were resolved, highlighting the potential of infrared multiple photon dissociation spectroscopy as a novel structural tool for carbohydrates.

Offshore oil spill response practices and emerging challenges.

PubMed

Li, Pu; Cai, Qinhong; Lin, Weiyun; Chen, Bing; Zhang, Baiyu

2016-09-15

Offshore oil spills are of tremendous concern due to their potential impact on economic and ecological systems. A number of major oil spills triggered worldwide consciousness of oil spill preparedness and response. Challenges remain in diverse aspects such as oil spill monitoring, analysis, assessment, contingency planning, response, cleanup, and decision support. This article provides a comprehensive review of the current situations and impacts of offshore oil spills, as well as the policies and technologies in offshore oil spill response and countermeasures. Correspondingly, new strategies and a decision support framework are recommended for improving the capacities and effectiveness of oil spill response and countermeasures. In addition, the emerging challenges in cold and harsh environments are reviewed with recommendations due to increasing risk of oil spills in the northern regions from the expansion of the Arctic Passage. Copyright © 2016 Elsevier Ltd. All rights reserved.

An Overview of Science Challenges Pertaining to our Understanding of Extreme Geomagnetically Induced Currents. Chapter 8

NASA Technical Reports Server (NTRS)

Ngwira, Chigomezyo M.; Pulkkinen, Antti A.

2018-01-01

Vulnerability of man-made infrastructure to Earth-directed space weather events is a serious concern for today's technology-dependent society. Space weather-driven geomagnetically induced currents (GICs) can disrupt operation of extended electrically conducting technological systems. The threat of adverse impacts on critical technological infrastructure, like power grids, oil and gas pipelines, and communication networks, has sparked renewed interest in extreme space weather. Because extreme space weather events have low occurrence rate but potentially high impact, this presents a major challenge for our understanding of extreme GIC activity. In this chapter, we discuss some of the key science challenges pertaining to our understanding of extreme events. In addition, we present an overview of GICs including highlights of severe impacts over the last 80 years and recent U.S. Federal actions relevant to this community.

Human Hemato-Lymphoid System Mice: Current Use and Future Potential for Medicine

PubMed Central

Rongvaux, Anthony; Takizawa, Hitoshi; Strowig, Till; Willinger, Tim; Eynon, Elizabeth E.

2014-01-01

To directly study complex human hemato-lymphoid system physiology and respective system-associated diseases in vivo, human-to-mouse xenotransplantation models for human blood and blood-forming cells and organs have been developed over the past three decades. We here review the fundamental requirements and the remarkable progress made over the past few years in improving these systems, the current major achievements reached by use of these models, and the future challenges to more closely model and study human health and disease and to achieve predictive preclinical testing of both prevention measures and potential new therapies. PMID:23330956

IT as an enabler of sustainable use of data from innovative technical components for assisted living.

PubMed

Knaup, Petra; Schöpe, Lothar

2012-01-01

The authors see the major potential of systematically processing data from AAL-technology in higher sustainability, higher technology acceptance, higher security, higher robustness, higher flexibility and better integration in existing structures and processes. This potential is currently underachieved and not yet systematically promoted. The authors have written a position paper on potential and necessity of substantial IT research enhancing Ambient Assisted Living (AAL) applications. This paper summarizes the most important challenges in the fields health care, data protection, operation and user interfaces. Research in medical informatics is necessary among others in the fields flexible authorization concept, medical information needs, algorithms to evaluate user profiles and visualization of aggregated data.

A potential method for lift evaluation from velocity field data

NASA Astrophysics Data System (ADS)

de Guyon-Crozier, Guillaume; Mulleners, Karen

2017-11-01

Computing forces from velocity field measurements is one of the challenges in experimental aerodynamics. This work focuses on low Reynolds flows, where the dynamics of the leading and trailing edge vortices play a major role in lift production. Recent developments in 2D potential flow theory, using discrete vortex models, have shown good results for unsteady wing motions. A method is presented to calculate lift from experimental velocity field data using a discrete vortex potential flow model. The model continuously adds new point vortices at leading and trailing edges whose circulations are set directly from vorticity measurements. Forces are computed using the unsteady Blasius equation and compared with measured loads.

Microalgae biorefineries: The Brazilian scenario in perspective.

PubMed

Brasil, B S A F; Silva, F C P; Siqueira, F G

2017-10-25

Biorefineries have the potential to meet a significant part of the growing demand for energy, fuels, chemicals and materials worldwide. Indeed, the bio-based industry is expected to play a major role in energy security and climate change mitigation during the 21th century. Despite this, there are challenges related to resource consumption, processing optimization and waste minimization that still need to be overcome. In this context, microalgae appear as a promising non-edible feedstock with advantages over traditional land crops, such as high productivity, continuous harvesting throughout the year and minimal problems regarding land use. Importantly, both cultivation and microalgae processing can take place at the same site, which increases the possibilities for process integration and a reduction in logistic costs at biorefinery facilities. This review describes the actual scenario for microalgae biorefineries integration to the biofuels and petrochemical industries in Brazil, while highlighting the major challenges and recent advances in microalgae large-scale production. Copyright © 2016 Elsevier B.V. All rights reserved.

Deployment of ACT antimalarials for treatment of malaria: challenges and opportunities

PubMed Central

Whitty, Christopher JM; Chandler, Clare; Ansah, Evelyn; Leslie, Toby; Staedke, Sarah G

2008-01-01

Following a long period when the effectiveness of existing mono-therapies for antimalarials was steadily declining with no clear alternative, most malaria-endemic countries in Africa and Asia have adopted artemisinin combination therapy (ACT) as antimalarial drug policy. Several ACT drugs exist and others are in the pipeline. If properly targeted, they have the potential to reduce mortality from malaria substantially. The major challenge now is to get the drugs to the right people. Current evidence suggests that most of those who need the drugs do not get them. Simultaneously, a high proportion of those who are given antimalarials do not in fact have malaria. Financial and other barriers mean that, in many settings, the majority of those with malaria, particularly the poorest, do not access formal healthcare, so the provision of free antimalarials via this route has only limited impact. The higher cost of ACT creates a market for fake drugs. Addressing these problems is now a priority. This review outlines current evidence, possible solutions and research priorities. PMID:19091041

Patch testers' opinions regarding diagnostic criteria for metal hypersensitivity reactions to metallic implants.

PubMed

Schalock, Peter C; Thyssen, Jacob P

2013-01-01

Metal hypersensitivity reactions to implanted devices remain a challenging and controversial topic. Diagnostic criteria and methods are not well delineated. Diagnostic criteria for hypersensitivity reactions after metallic device implantation are evaluated in this study by a multinational group of patch testers using Thyssen's previously published criteria. A total of 119 dermatologists at the 2012 European Contact Dermatitis Society and 2013 American Contact Dermatitis Society meetings answered a survey regarding their opinions on topics relating to metal hypersensitivity. Four major and 5 minor diagnostic criteria emerged. Approximately 80% of respondents found the following criteria useful (major criteria): chronic dermatitis beginning weeks to months after metallic implantation, eruption overlying the metal implant, positive patch test to a metal component of the implant, and complete clearing after removal of the potentially allergenic implant. Minor criteria (<61% of respondents) were as follows: systemic allergic dermatitis reaction, therapy-resistant dermatitis, morphology consistent with dermatitis, histology consistent with allergic contact dermatitis, and a positive in vitro test to metals (eg, lymphocyte transformation test). In the challenging situation such as a symptomatic or failing orthopedic device, applying these 4 major criteria and the 5 supportive minor criteria may be useful for guiding decision making.

Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

PubMed Central

Chowdhury, Fabliha Ahmed; Hossain, Md Kamal; Mostofa, A. G. M.; Akbor, Maruf Mohammad

2018-01-01

Glioblastoma multiforme (GBM) is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ), the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM. PMID:29651429

The Therapeutic Potential of Anti-Inflammatory Exerkines in the Treatment of Atherosclerosis

PubMed Central

Yu, Megan; Tsai, Sheng-Feng; Kuo, Yu-Min

2017-01-01

Although many cardiovascular (CVD) medications, such as antithrombotics, statins, and antihypertensives, have been identified to treat atherosclerosis, at most, many of these therapeutic agents only delay its progression. A growing body of evidence suggests physical exercise could be implemented as a non-pharmacologic treatment due to its pro-metabolic, multisystemic, and anti-inflammatory benefits. Specifically, it has been discovered that certain anti-inflammatory peptides, metabolites, and RNA species (collectively termed “exerkines”) are released in response to exercise that could facilitate these benefits and could serve as potential therapeutic targets for atherosclerosis. However, much of the relationship between exercise and these exerkines remains unanswered, and there are several challenges in the discovery and validation of these exerkines. This review primarily highlights major anti-inflammatory exerkines that could serve as potential therapeutic targets for atherosclerosis. To provide some context and comparison for the therapeutic potential of exerkines, the anti-inflammatory, multisystemic benefits of exercise, the basic mechanisms of atherosclerosis, and the limited efficacies of current anti-inflammatory therapeutics for atherosclerosis are briefly summarized. Finally, key challenges and future directions for exploiting these exerkines in the treatment of atherosclerosis are discussed. PMID:28608819

Biosimilars: Opportunities to Promote Optimization Through Payer and Provider Collaboration.

PubMed

Manolis, Chronis H; Rajasenan, Kiran; Harwin, William; McClelland, Scott; Lopes, Maria; Farnum, Carolyn

2016-09-01

A panel was convened that consisted of 1 medical director, 2 pharmacy directors, and 2 oncologists, who represented the University of Pittsburgh Medical Center Health Plan, an integrated delivery network, and Florida Blue, a progressive regional health plan. This panel met in order to share ideas, discuss challenges, and develop practical solutions to promote optimal utilization in order to encourage collaboration between payers and providers to help ensure the success of biosimilar entrants into the marketplace. Live meetings were conducted in Orlando, Florida, and Pittsburgh, Pennsylvania, and were followed by virtual meetings to solidify ideas and concepts for this supplement. It is important for biosimilar manufacturers to identify potential payer, provider, and patient obstacles in order to develop strategic and tactical plans to preemptively address these potential obstacles. Gathering payer and provider insights will shed light on various issues such as access and reimbursement. Biosimilar manufacturers must be proactive in the education of payers, providers, and patients to ensure access to biosimilars. A strong factor emphasized among this group was that the assumption surrounding biosimilar development and use is the potential for health care cost savings. According to the panel, payers and providers must carefully consider economic implications and potential cost-effectiveness in order to increase the acceptance or understanding of biosimilars in clinical practice. The group identified 3 major challenges surrounding biosimilar adoption: (1) provider confidence in biosimilar education and clinical value, (2) provider confidence in reimbursement for new biosimilars, and (3) creating shared payer and provider cost-savings. After identification of the 3 challenges, the group posed potential solutions to help with biosimilar adoption.

Women's infertility: challenges for practice.

PubMed

Carryer, J; Maclean, S

1998-03-01

Infertility is an issue for men and women but it is women who experience the majority of the diagnostic and treatment procedures. Nurses and midwives care for women in a variety of settings in which infertility is managed. This management is currently characterised by an escalation in related technologies and there is the potential for prolonged and complex endeavours to achieve a pregnancy. This paper reviews some pertinent literature from nursing, medicine, feminist scholars and the popular press to consider the ways in which infertility is understood and experienced. The challenge for nurses and midwives is in negotiating the differing perspectives in order to provide appropriate care to each individual woman as she experiences infertility and its management.

A climate-compatible approach to development practice by international humanitarian NGOs.

PubMed

Clarke, Matthew; de Cruz, Ian

2015-01-01

If current climate-change predictions prove accurate, non-linear change, including potentially catastrophic change, is possible and the environments in which international humanitarian NGOs operate will change figuratively and literally. This paper proposes that a new approach to development is required that takes changing climate into account. This 'climate-compatible approach' to development is a bleak shift from some of the current orthodox positions and will be a major challenge to international humanitarian NGOs working with the most vulnerable. However, it is necessary to address the challenges and context such NGOs face, and the need to be resilient and adaptive to these changes. © 2014 The Author(s). Disasters © Overseas Development Institute, 2014.

Evolving Use of Natriuretic Peptides as Part of Strategies for Heart Failure Prevention.

PubMed

McDonald, Ken; Wilkinson, Mark

2017-01-01

Heart failure (HF) remains one of the major cardiovascular challenges to the Western world. Once established, HF is characterized by compromised life expectancy and quality of life with considerable dependence on hospital care for episodic clinical deterioration. Much is understood about the risk factors that predispose to the development of HF. With such a broad range of factors, it is clear that there is a large population at risk, potentially in excess of 25% of the adult population. Therein lies the major challenge at the outset of our efforts to prevent HF. With such a large population at risk, how do we develop an effective prevention strategy? HF prevention requires a multimodal approach. In this review, we focus primarily on the role of natriuretic peptide (NP) as a tool in a prevention strategy. Prevention of HF is a major public health challenge, underlined by the concerning epidemiological trends, the associated costs, and the continued difficulty to find effective therapies for the growing number of patients with preserved systolic function HF. Population-based approaches focusing on lifestyle and risk factor control have made some impact but not to a satisfactory level and also tend to result in a uniform approach across a population with different risk profiles. Individualizing risk is therefore required, with emerging data indicating that NP-guided risk stratification and intervention can reduce downstream incident HF and other cardiovascular events. © 2016 American Association for Clinical Chemistry.

Pluripotent Stem Cells for Retinal Tissue Engineering: Current Status and Future Prospects.

PubMed

Singh, Ratnesh; Cuzzani, Oscar; Binette, François; Sternberg, Hal; West, Michael D; Nasonkin, Igor O

2018-04-19

The retina is a very fine and layered neural tissue, which vitally depends on the preservation of cells, structure, connectivity and vasculature to maintain vision. There is an urgent need to find technical and biological solutions to major challenges associated with functional replacement of retinal cells. The major unmet challenges include generating sufficient numbers of specific cell types, achieving functional integration of transplanted cells, especially photoreceptors, and surgical delivery of retinal cells or tissue without triggering immune responses, inflammation and/or remodeling. The advances of regenerative medicine enabled generation of three-dimensional tissues (organoids), partially recreating the anatomical structure, biological complexity and physiology of several tissues, which are important targets for stem cell replacement therapies. Derivation of retinal tissue in a dish creates new opportunities for cell replacement therapies of blindness and addresses the need to preserve retinal architecture to restore vision. Retinal cell therapies aimed at preserving and improving vision have achieved many improvements in the past ten years. Retinal organoid technologies provide a number of solutions to technical and biological challenges associated with functional replacement of retinal cells to achieve long-term vision restoration. Our review summarizes the progress in cell therapies of retina, with focus on human pluripotent stem cell-derived retinal tissue, and critically evaluates the potential of retinal organoid approaches to solve a major unmet clinical need-retinal repair and vision restoration in conditions caused by retinal degeneration and traumatic ocular injuries. We also analyze obstacles in commercialization of retinal organoid technology for clinical application.

Methodological challenges when evaluating potential off-label prescribing of drugs using electronic health care databases: A case study of dabigatran etexilate in Europe.

PubMed

Cainzos-Achirica, Miguel; Varas-Lorenzo, Cristina; Pottegård, Anton; Asmar, Joelle; Plana, Estel; Rasmussen, Lotte; Bizouard, Geoffray; Forns, Joan; Hellfritzsch, Maja; Zint, Kristina; Perez-Gutthann, Susana; Pladevall-Vila, Manel

2018-03-23

To report and discuss estimated prevalence of potential off-label use and associated methodological challenges using a case study of dabigatran. Observational, cross-sectional study using 3 databases with different types of clinical information available: Cegedim Strategic Data Longitudinal Patient Database (CSD-LPD), France (cardiologist panel, n = 1706; general practitioner panel, n = 2813; primary care data); National Health Databases, Denmark (n = 28 619; hospital episodes and dispensed ambulatory medications); and Clinical Practice Research Datalink (CPRD), UK (linkable to Hospital Episode Statistics [HES], n = 2150; not linkable, n = 1285; primary care data plus hospital data for HES-linkable patients). August 2011 to August 2015. Two definitions were used to estimate potential off-label use: a broad definition of on-label prescribing using codes for disease indication (eg, atrial fibrillation [AF]), and a restrictive definition excluding patients with conditions for which dabigatran is not indicated (eg, valvular AF). Prevalence estimates under the broad definition ranged from 5.7% (CPRD-HES) to 34.0% (CSD-LPD) and, under the restrictive definition, from 17.4% (CPRD-HES) to 44.1% (CSD-LPD). For the majority of potential off-label users, no diagnosis potentially related to anticoagulant use was identified. Key methodological challenges were the limited availability of detailed clinical information, likely leading to overestimation of off-label use, and differences in the information available, which may explain the disparate prevalence estimates across data sources. Estimates of potential off-label use should be interpreted cautiously due to limitations in available information. In this context, CPRD HES-linkable estimates are likely to be the most accurate. Copyright © 2018 John Wiley & Sons, Ltd.

The Adverse Drug Reactions from Patient Reports in Social Media Project: Five Major Challenges to Overcome to Operationalize Analysis and Efficiently Support Pharmacovigilance Process

PubMed Central

Dahamna, Badisse; Guillemin-Lanne, Sylvie; Darmoni, Stefan J; Faviez, Carole; Huot, Charles; Katsahian, Sandrine; Leroux, Vincent; Pereira, Suzanne; Richard, Christophe; Schück, Stéphane; Souvignet, Julien; Lillo-Le Louët, Agnès; Texier, Nathalie

2017-01-01

Background Adverse drug reactions (ADRs) are an important cause of morbidity and mortality. Classical Pharmacovigilance process is limited by underreporting which justifies the current interest in new knowledge sources such as social media. The Adverse Drug Reactions from Patient Reports in Social Media (ADR-PRISM) project aims to extract ADRs reported by patients in these media. We identified 5 major challenges to overcome to operationalize the analysis of patient posts: (1) variable quality of information on social media, (2) guarantee of data privacy, (3) response to pharmacovigilance expert expectations, (4) identification of relevant information within Web pages, and (5) robust and evolutive architecture. Objective This article aims to describe the current state of advancement of the ADR-PRISM project by focusing on the solutions we have chosen to address these 5 major challenges. Methods In this article, we propose methods and describe the advancement of this project on several aspects: (1) a quality driven approach for selecting relevant social media for the extraction of knowledge on potential ADRs, (2) an assessment of ethical issues and French regulation for the analysis of data on social media, (3) an analysis of pharmacovigilance expert requirements when reviewing patient posts on the Internet, (4) an extraction method based on natural language processing, pattern based matching, and selection of relevant medical concepts in reference terminologies, and (5) specifications of a component-based architecture for the monitoring system. Results Considering the 5 major challenges, we (1) selected a set of 21 validated criteria for selecting social media to support the extraction of potential ADRs, (2) proposed solutions to guarantee data privacy of patients posting on Internet, (3) took into account pharmacovigilance expert requirements with use case diagrams and scenarios, (4) built domain-specific knowledge resources embeding a lexicon, morphological rules, context rules, semantic rules, syntactic rules, and post-analysis processing, and (5) proposed a component-based architecture that allows storage of big data and accessibility to third-party applications through Web services. Conclusions We demonstrated the feasibility of implementing a component-based architecture that allows collection of patient posts on the Internet, near real-time processing of those posts including annotation, and storage in big data structures. In the next steps, we will evaluate the posts identified by the system in social media to clarify the interest and relevance of such approach to improve conventional pharmacovigilance processes based on spontaneous reporting. PMID:28935617

Joint Operating Environment: Trends and Challenges for the Future Joint Force Through 2030

DTIC Science & Technology

2007-12-01

unmanned underwater vehicles loom on the horizon that can be swarmed against our ports and cities. Self - healing , networked minefields will... robots in an effort to provide the basic physical labor needed by the society. Russia has seen a major withdrawal of it population from the Far...of criminal elements. International organized crime, motivated by greed and self -interest, may increase as potential security threats to the

Africa and the Arab Spring: A New Era of Democratic Expectations

DTIC Science & Technology

2011-11-01

legislatures approve major aid packages (from the World Bank or Millennium Challenge Corporation , for example) as well as contracts with resource extraction...Moreover, Libyan businesses and finance institutions closely aligned with the Gaddafi regime had invested billions of dollars in hotels, banks , petrol...DC: The World Bank , 2011); UNESCO Institute for Statistics, 2011. 52 “Lions on the Move: The Progress and Potential of Africa’s Economies,” McKinsey

On the materials basis of modern society

PubMed Central

Graedel, T. E.; Nassar, N. T.; Reck, Barbara K.

2015-01-01

It is indisputable that modern life is enabled by the use of materials in its technologies. Those technologies do many things very well, largely because each material is used for purposes to which it is exquisitely fitted. The result over time has been a steady increase in product performance. We show that this materials complexity has markedly increased in the past half-century and that elemental life cycle analyses characterize rates of recycling and loss. A further concern is that of possible scarcity of some of the elements as their use increases. Should materials availability constraints occur, the use of substitute materials comes to mind. We studied substitution potential by generating a comprehensive summary of potential substitutes for 62 different metals in all their major uses and of the performance of the substitutes in those applications. As we show herein, for a dozen different metals, the potential substitutes for their major uses are either inadequate or appear not to exist at all. Further, for not 1 of the 62 metals are exemplary substitutes available for all major uses. This situation largely decouples materials substitution from price, thereby forcing material design changes to be primarily transformative rather than incremental. As wealth and population increase worldwide in the next few decades, scientists will be increasingly challenged to maintain and improve product utility by designing new and better materials, but doing so under potential constraints in resource availability. PMID:24297915

Planetary Atmosphere and Surfaces Chamber (PASC): A Platform to Address Various Challenges in Astrobiology

NASA Astrophysics Data System (ADS)

Mateo-Marti, Eva

2014-08-01

The study of planetary environments of astrobiological interest has become a major challenge. Because of the obvious technical and economical limitations on in situ planetary exploration, laboratory simulations are one of the most feasible research options to make advances both in planetary science and in developing a consistent description of the origin of life. With this objective in mind, we applied vacuum technology to the design of versatile vacuum chambers devoted to the simulation of planetary atmospheres' conditions. These vacuum chambers are able to simulate atmospheres and surface temperatures representative of the majority of planetary objects, and they are especially appropriate for studying the physical, chemical and biological changes induced in a particular sample by in situ irradiation or physical parameters in a controlled environment. Vacuum chambers are a promising potential tool in several scientific and technological fields, such as engineering, chemistry, geology and biology. They also offer the possibility of discriminating between the effects of individual physical parameters and selected combinations thereof. The implementation of our vacuum chambers in combination with analytical techniques was specifically developed to make feasible the in situ physico-chemical characterization of samples. Many wide-ranging applications in astrobiology are detailed herein to provide an understanding of the potential and flexibility of these experimental systems. Instruments and engineering technology for space applications could take advantage of our environment-simulation chambers for sensor calibration. Our systems also provide the opportunity to gain a greater understanding of the chemical reactivity of molecules on surfaces under different environments, thereby leading to a greater understanding of interface processes in prebiotic chemical reactions and facilitating studies of UV photostability and photochemistry on surfaces. Furthermore, the stability and presence of certain minerals on planetary surfaces and the potential habitability of microorganisms under various planetary environmental conditions can be studied using our apparatus. Therefore, these simulation chambers can address multiple different challenging and multidisciplinary astrobiological studies.

Immunization with Live Human Rhinovirus (HRV) 16 Induces Protection in Cotton Rats against HRV14 Infection.

PubMed

Patel, Mira C; Pletneva, Lioubov M; Boukhvalova, Marina S; Vogel, Stefanie N; Kajon, Adriana E; Blanco, Jorge C G

2017-01-01

Human rhinoviruses (HRVs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against HRVs are available to prevent or mitigate HRV infection. There are more than 150 antigenically heterogeneous HRV serotypes, with ∼90 HRVs belonging to major group species A and B. Development of small animal models that are susceptible to infection with major group HRVs would be beneficial for vaccine research. Previously, we showed that the cotton rat ( Sigmodon hispidus ) is semi-permissive to HRV16 (major group, species HRV-A virus) infection, replicating in the upper and lower respiratory tracts with measurable pathology, mucus production, and expression of inflammatory mediators. Herein, we report that intranasal infection of cotton rats with HRV14 (major group, species HRV-B virus) results in isolation of infectious virus from the nose and lung. Similar to HRV16, intramuscular immunization with live HRV14 induces homologous protection that correlated with high levels of serum neutralizing antibodies. Vaccination and challenge experiments with HRV14 and HRV16 to evaluate the development of cross-protective immunity demonstrate that intramuscular immunization with live HRV16 significantly protects animals against HRV14 challenge. Determination of the immunological mechanisms involved in heterologous protection and further characterization of infection with other major HRV serotypes in the cotton rat could enhance the robustness of the model to define heterotypic relationships between this diverse group of viruses and thereby increase its potential for development of a multi-serotype HRV vaccine.

Challenges and Opportunities of Airborne Metagenomics

PubMed Central

Behzad, Hayedeh; Gojobori, Takashi; Mineta, Katsuhiko

2015-01-01

Recent metagenomic studies of environments, such as marine and soil, have significantly enhanced our understanding of the diverse microbial communities living in these habitats and their essential roles in sustaining vast ecosystems. The increase in the number of publications related to soil and marine metagenomics is in sharp contrast to those of air, yet airborne microbes are thought to have significant impacts on many aspects of our lives from their potential roles in atmospheric events such as cloud formation, precipitation, and atmospheric chemistry to their major impact on human health. In this review, we will discuss the current progress in airborne metagenomics, with a special focus on exploring the challenges and opportunities of undertaking such studies. The main challenges of conducting metagenomic studies of airborne microbes are as follows: 1) Low density of microorganisms in the air, 2) efficient retrieval of microorganisms from the air, 3) variability in airborne microbial community composition, 4) the lack of standardized protocols and methodologies, and 5) DNA sequencing and bioinformatics-related challenges. Overcoming these challenges could provide the groundwork for comprehensive analysis of airborne microbes and their potential impact on the atmosphere, global climate, and our health. Metagenomic studies offer a unique opportunity to examine viral and bacterial diversity in the air and monitor their spread locally or across the globe, including threats from pathogenic microorganisms. Airborne metagenomic studies could also lead to discoveries of novel genes and metabolic pathways relevant to meteorological and industrial applications, environmental bioremediation, and biogeochemical cycles. PMID:25953766

Extent of alcohol prohibition in civil policy in Muslim majority countries: the impact of globalization.

PubMed

Al-Ansari, Basma; Thow, Anne-Marie; Day, Carolyn A; Conigrave, Katherine M

2016-10-01

Many policies have been introduced to reduce alcohol harm in different countries. However, Muslim majority countries (MMCs), where the major religion (Islam) prohibits alcohol consumption, have less well-developed civil alcohol policies. Overall, MMCs have low prevalence of alcohol consumption, although recently most MMCs have been undergoing transition, which has sometimes increased pressure for alcohol availability and impacted on social practices, alcohol policies and broader public health. Globalization, the influence of the global alcohol industry, recent governmental transition or political instability and the presence of immigrants from non-Muslim countries can all affect civil alcohol policy. In this context, consumption overall has increased compared with two decades ago. This paper presents an overview of current civil alcohol policy, with regard to the presence or absence of alcohol prohibition, and provides an insight into the legal availability of alcohol in MMCs and the challenges facing policymakers. English, Arabic and Persian language sources were examined, using PubMed, government websites for each country and the World Health Organization (WHO). Some of the challenges MMCs may face in developing alcohol policies are explored, including the need to interact with the global economy and the potential influence of the alcohol industry. Muslim majority countries have adopted a range of civil alcohol policies in recent decades. There is a pressing need for better data and to support Muslim majority countries in alcohol policy development. Lessons from Muslim majority countries can help to inform other parts of the world. © 2015 Society for the Study of Addiction.

Breast cancer detection in rotational thermography images using texture features

NASA Astrophysics Data System (ADS)

Francis, Sheeja V.; Sasikala, M.; Bhavani Bharathi, G.; Jaipurkar, Sandeep D.

2014-11-01

Breast cancer is a major cause of mortality in young women in the developing countries. Early diagnosis is the key to improve survival rate in cancer patients. Breast thermography is a diagnostic procedure that non-invasively images the infrared emissions from breast surface to aid in the early detection of breast cancer. Due to limitations in imaging protocol, abnormality detection by conventional breast thermography, is often a challenging task. Rotational thermography is a novel technique developed in order to overcome the limitations of conventional breast thermography. This paper evaluates this technique's potential for automatic detection of breast abnormality, from the perspective of cold challenge. Texture features are extracted in the spatial domain, from rotational thermogram series, prior to and post the application of cold challenge. These features are fed to a support vector machine for automatic classification of normal and malignant breasts, resulting in a classification accuracy of 83.3%. Feature reduction has been performed by principal component analysis. As a novel attempt, the ability of this technique to locate the abnormality has been studied. The results of the study indicate that rotational thermography holds great potential as a screening tool for breast cancer detection.

Screening for Barrett’s Esophagus and Esophageal Adenocarcinoma: Rationale, Recent Progress, Challenges and Future Directions

PubMed Central

Sami, Sarmed S.; Ragunath, Krish; Iyer, Prasad G.

2014-01-01

As the incidence and mortality of esophageal adenocarcinoma continue to increase, strategies to counter this need to be explored. Screening for Barrett’s esophagus, which is the known precursor of a large majority of adenocarcinomas, has been debated without a firm consensus. Given evidence for and against perceived benefits of screening, the multitude of challenges in the implementation of such a strategy and in the downstream management of subjects with Barrett’s esophagus who could be diagnosed by screening, support for screening has been modest. Recent advances in form of development and initial accuracy of non-invasive tools for screening, risk assessment tools and biomarker panels to risk stratify subjects with BE, have spurred renewed interest in the early detection of Barrett’s esophagus and related neoplasia, particularly with the advent of effective endoscopic therapy. In this review, we explore in depth, the potential rationale for screening for Barrett’s esophagus, recent advances which have the potential of making screening feasible and also highlight some of the challenges which will have to be overcome to develop an effective approach to improve the outcomes of subjects with esophageal adenocarcinoma. PMID:24887058

Sources and sinks of carbon in boreal ecosystems of interior Alaska: a review

USGS Publications Warehouse

Douglas, Thomas A.; Jones, Miriam C.; Hiemstra, Christopher A.

2014-01-01

Boreal regions store large quantities of carbon but are increasingly vulnerable to carbon loss due to disturbance and climate warming. The boreal region, underlain by discontinuous permafrost, presents a challenging landscape for itemizing current and potential carbon sources and sinks in the boreal soil and vegetation. The roles of fire, forest succession, and the presence (or absence) of permafrost on carbon cycle, vegetation, and hydrologic processes have been the focus of multidisciplinary research in this area for the past 20 years. However, projections of a warming future climate, an increase in fire severity and extent, and the potential degradation of permafrost could lead to major landscape process changes over the next 20 to 50 years. This provides a major challenge for predicting how the interplay between land management activities and impacts of climate warming will affect carbon sources and sinks in Interior Alaska. To assist land managers in adapting and managing for potential changes in the Interior Alaska carbon cycle we developed this review paper incorporating an overview of the climate, ecosystem processes, vegetation types, and soil regimes in Interior Alaska with a focus on ramifications for the carbon cycle. Our objective is to provide a synthesis of the most current carbon storage estimates and measurements to support policy and land management decisions on how to best manage carbon sources and sinks in Interior Alaska. To support this we have surveyed relevant peer reviewed estimates of carbon stocks in aboveground and belowground biomass for Interior Alaska boreal ecosystems. We have also summarized methane and carbon dioxide fluxes from the same ecosystems. These data have been converted into the same units to facilitate comparison across ecosystem compartments. We identify potential changes in the carbon cycle with climate change and human disturbance including how compounding disturbances can affect the boreal system. Finally, we provide recommendations to address the challenges facing land managers in efforts to manage carbon cycle processes. The results of this study can be used for carbon cycle management in other locations within the boreal biome which encompass a broad distribution from 45° to 83° north.

Roadmap on neurophotonics

NASA Astrophysics Data System (ADS)

Cho, Yong Ku; Zheng, Guoan; Augustine, George J.; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S.; Vellekoop, Ivo M.; Booth, Martin J.; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2016-09-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken.

Contact lens wearers' experiences while trekking in the Khumbu region/Nepal: a cross-sectional survey.

PubMed

Bauer, Irmgard L

2015-01-01

Safe contact lens wear depends on a hygiene regime and lens-appropriate wear patterns which may be compromised during travel in remote and wilderness areas. The purpose of this study was to describe the experience of contact lens wearers while trekking at high-altitude in Nepal. For this descriptive study, trekkers with contact lenses were recruited in Lukla and invited to complete an online-questionnaire on trip preparation, contact lens use, care and experiences, and possible changes for future travel. Quantitative data were analysed using SurveyMonkey; content analysis applied to qualitative responses. The majority of the 158 participants (124; 78.48%) reported no problems with their lenses (daily disposables, soft lenses, extended-wear lenses, hard/rigid lenses) during their stay although dry air, dust, wind, cold temperatures, and difficult hygiene maintenance were challenging. Freezing lenses and freezing solutions were additional challenges. Thirty-four (21.52%) experienced a variety of problems. Improvements were requested from manufacturers. Lodges should provide better access to clean water, mirrors and lighting. Almost 60% of participants had not sought any pre-travel health advice. Remote and wilderness areas provide a challenge for appropriate contact lens wear and care. The decision between the potential risk of infection due to touching lenses (daily disposables, soft/hard lenses) and the potential risk of corneal erosion (extended-wear lenses) needs to be made in pre-travel consultations. Travel health professionals and travel agencies should remind CL-wearing trekkers to carefully assess their wear and care routine to accommodate potentially challenging conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Roadmap on neurophotonics

PubMed Central

Cho, Yong Ku; Zheng, Guoan; Augustine, George J; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S; Vellekoop, Ivo M; Booth, Martin J; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2017-01-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken. PMID:28386392

The rocky road to the top: why talent needs trauma.

PubMed

Collins, Dave; MacNamara, Aine

2012-11-01

The increasingly well funded and high-tech world of talent development (TD) represents an important investment for most sports. Reflecting traditional concepts of challenge and focus, the vast majority of such systems expend a great deal of effort maximizing support to the young athletes and trying to counter the impact of naturally occurring life stressors. In this article, we suggest that much of this effort is misdirected; that, in fact, talented potential can often benefit from, or even need, a variety of challenges to facilitate eventual adult performance. Our argument is built on evidence that such challenges are more common in athletes who reach the top, together with a critical consideration of the modus operandi and impact of psychological/character-focused interventions such as mental toughness and resilience. In conclusion, we explore some implications for the design and conduct of optimum academies and TD environments.

Challenges and perspectives in quantitative NMR.

PubMed

Giraudeau, Patrick

2017-01-01

This perspective article summarizes, from the author's point of view at the beginning of 2016, the major challenges and perspectives in the field of quantitative NMR. The key concepts in quantitative NMR are first summarized; then, the most recent evolutions in terms of resolution and sensitivity are discussed, as well as some potential future research directions in this field. A particular focus is made on methodologies capable of boosting the resolution and sensitivity of quantitative NMR, which could open application perspectives in fields where the sample complexity and the analyte concentrations are particularly challenging. These include multi-dimensional quantitative NMR and hyperpolarization techniques such as para-hydrogen-induced polarization or dynamic nuclear polarization. Because quantitative NMR cannot be dissociated from the key concepts of analytical chemistry, i.e. trueness and precision, the methodological developments are systematically described together with their level of analytical performance. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The chronic kidney disease epidemic: a challenge for nephrology training programs.

PubMed

Kohan, Donald E; Rosenberg, Mark E

2009-09-01

A major challenge facing the nephrology community in the United States is the training of adequate numbers of nephrologists to meet patient care and research needs. There is particular cause for concern because of the increasing incidence and prevalence of patients with chronic kidney disease. Data on the clinical and research nephrology workforce are incomplete or absent. However, the number of such individuals likely is inadequate to meet current and projected needs. To solve these workforce shortages, significant issues with regard to clinical and research training need to be addressed. These include funding of fellowship training, increasing the pipeline of medical students and internal medicine residents, and enhancing interest in nephrology among international and particularly US medical graduates. This review discusses these challenges facing the renal community, with emphasis on the care, prevention, and treatment of chronic kidney disease, and identifies potential pathways to developing solutions.

Toward a Social Psychophysics of Face Communication.

PubMed

Jack, Rachael E; Schyns, Philippe G

2017-01-03

As a highly social species, humans are equipped with a powerful tool for social communication-the face. Although seemingly simple, the human face can elicit multiple social perceptions due to the rich variations of its movements, morphology, and complexion. Consequently, identifying precisely what face information elicits different social perceptions is a complex empirical challenge that has largely remained beyond the reach of traditional methods. In the past decade, the emerging field of social psychophysics has developed new methods to address this challenge, with the potential to transfer psychophysical laws of social perception to the digital economy via avatars and social robots. At this exciting juncture, it is timely to review these new methodological developments. In this article, we introduce and review the foundational methodological developments of social psychophysics, present work done in the past decade that has advanced understanding of the face as a tool for social communication, and discuss the major challenges that lie ahead.

The Public Health Challenge.

ERIC Educational Resources Information Center

Ember, Lois R.

1987-01-01

Discussed are public health challenges related to Acquired Immune Deficiency Syndrome (AIDS). A major challenge is changing habits and damping incipient fear. Education is considered by some to be one of the major public health weapons. Described are various programs, legal issues, and policies being considered and implemented. (RH)

Demand Response and Energy Storage Integration Study

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

Ma, Ookie; Cheung, Kerry; Olsen, Daniel J.

2016-03-01

Demand response and energy storage resources present potentially important sources of bulk power system services that can aid in integrating variable renewable generation. While renewable integration studies have evaluated many of the challenges associated with deploying large amounts of variable wind and solar generation technologies, integration analyses have not yet fully incorporated demand response and energy storage resources. This report represents an initial effort in analyzing the potential integration value of demand response and energy storage, focusing on the western United States. It evaluates two major aspects of increased deployment of demand response and energy storage: (1) Their operational valuemore » in providing bulk power system services and (2) Market and regulatory issues, including potential barriers to deployment.« less

Potential Use of Classroom Response Systems (CRS, Clickers) in Foods, Nutrition, and Dietetics Higher Education.

PubMed

Gould, Susan Martin

2016-10-01

Although hundreds of articles have been published about the use of classroom response systems (CRS, clickers) in higher education, few address the use in foods, nutrition, and dietetics courses, especially upper-division, major courses. This technology has the potential to increase student engagement, motivation, assessment, and, possibly, learning. Thoughtfully designed questions may stimulate discussions, especially about challenging nutrition topics. This article presents the viability and potential benefits for the use of CRS in foods, nutrition, and dietetics classes through a brief literature summary, overview of the author's experiences, and guidance for implementing this technology. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Demand Response and Energy Storage Integration Study

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

Ma, Ookie; Cheung, Kerry

Demand response and energy storage resources present potentially important sources of bulk power system services that can aid in integrating variable renewable generation. While renewable integration studies have evaluated many of the challenges associated with deploying large amounts of variable wind and solar generation technologies, integration analyses have not yet fully incorporated demand response and energy storage resources. This report represents an initial effort in analyzing the potential integration value of demand response and energy storage, focusing on the western United States. It evaluates two major aspects of increased deployment of demand response and energy storage: (1) Their operational valuemore » in providing bulk power system services and (2) Market and regulatory issues, including potential barriers to deployment.« less

Coarse Grained Model for Biological Simulations: Recent Refinements and Validation

PubMed Central

Vicatos, Spyridon; Rychkova, Anna; Mukherjee, Shayantani; Warshel, Arieh

2014-01-01

Exploring the free energy landscape of proteins and modeling the corresponding functional aspects presents a major challenge for computer simulation approaches. This challenge is due to the complexity of the landscape and the enormous computer time needed for converging simulations. The use of various simplified coarse grained (CG) models offers an effective way of sampling the landscape, but most current models are not expected to give a reliable description of protein stability and functional aspects. The main problem is associated with insufficient focus on the electrostatic features of the model. In this respect our recent CG model offers significant advantage as it has been refined while focusing on its electrostatic free energy. Here we review the current state of our model, describing recent refinement, extensions and validation studies while focusing on demonstrating key applications. These include studies of protein stability, extending the model to include membranes and electrolytes and electrodes as well as studies of voltage activated proteins, protein insertion trough the translocon, the action of molecular motors and even the coupling of the stalled ribosome and the translocon. Our example illustrates the general potential of our approach in overcoming major challenges in studies of structure function correlation in proteins and large macromolecular complexes. PMID:25050439

Sirtuins in neurodegenerative diseases: an update on potential mechanisms

PubMed Central

Min, Sang-Won; Sohn, Peter D.; Cho, Seo-Hyun; Swanson, Raymond A.; Gan, Li

2013-01-01

Silent information regulator 2 proteins (sirtuins or SIRTs) are a group of deacetylases (or deacylases) whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). Compelling evidence supports that sirtuins play major roles in many aspects of physiology, especially in pathways related to aging – the predominant and unifying risk factor for neurodegenerative diseases. In this review, we highlight the molecular mechanisms underlying the protective effects of sirtuins in neurodegenerative diseases, focusing on protein homeostasis, neural plasticity, mitochondrial function, and sustained chronic inflammation. We will also examine the potential and challenges of targeting sirtuin pathways to block these pathogenic pathways. PMID:24093018

Beyond inpatient and outpatient care: alternative model for hypertension management.

PubMed

Ho, P Michael; Rumsfeld, John S

2006-10-19

Hypertension is a major contributor to worldwide cardiovascular mortality, however, only one-third of patients with hypertension have their blood pressure treated to guideline recommended levels. To improve hypertension control, there may need to be a fundamental shift in care delivery, one that is population-based and simultaneously addresses patient, provider and system barriers. One potential approach is home-based disease management, based on the triad of home monitoring, team care, and patient self-care. Although there may be challenges to achieving the vision of home-based disease management, there are tremendous potential benefits of such an approach for reducing the global burden of cardiovascular disease.

Balancing the professional and personal.

PubMed

Armstrong, Alicia Y; Alvero, Ruben J; Dunlow, Susan; Nace, Mary Catherine; Baker, Valerie; Stewart, Elizabeth A

2009-01-01

To review the common roles that physicians pursue away from work and identify related challenges and potential solutions, so that individuals can develop a personalized plan for success in each of the areas. Literature review. University-based and university-affiliated medical centers. No subjects were involved in this literature review. Literature searches in Entrez PubMed and the following Websites: http://www.apgo.org, http://www.psychiatrictimes.com, as well as other data sources. Results of physician surveys and summaries of strategies for achieving work-personal life balance. According to surveys of physicians in various specialties, a majority of physicians have high levels of job, marital, and parental satisfaction. However, professional and personal challenges faced by physicians include struggle with time management, lack of mentorship, and difficulty maintaining intimate relationships. Multiple potentially effective strategies have been described in the literature, including exerting control over hours worked, taking a long view of life that acknowledges the need for changing priorities over time, developing communication skills, seeking counseling services if needed that focus on physician relationships, and simplifying home life whenever possible. Although there are unique challenges in being a physician, partner, and parent, many of the professional challenges faced by physicians are common to many adults in the United States. Self-assessment may help individuals to clarify priorities and develop strategies that can lead to improved personal satisfaction.

Integrated Approach of Agri-nanotechnology: Challenges and Future Trends

PubMed Central

Mishra, Sandhya; Keswani, Chetan; Abhilash, P. C.; Fraceto, Leonardo F.; Singh, Harikesh Bahadur

2017-01-01

Nanotechnology representing a new frontier in modern agriculture is anticipated to become a major thrust in near future by offering potential applications. This integrating approach, i.e., agri-nanotechnology has great potential to cope with global challenges of food production/security, sustainability and climate change. However, despite the potential benefits of nanotechnology in agriculture so far, their relevance has not reached up to the field conditions. The elevating concerns about fate, transport, bioavailability, nanoparticles toxicity and inappropriateness of regulatory framework limit the complete acceptance and inclination to adopt nanotechnologies in agricultural sector. Moreover, the current research trends lack realistic approach that fail to attain comprehensive knowledge of risk assessment factors and further toxicity of nanoparticles toward agroecosystem components viz. plant, soil, soil microbiomes after their release into the environment. Hence in the present review we attempt to suggest certain key points to be addressed in the current and future agri-nanotechnology researches on the basis of recognized knowledge gaps with strong recommendation of incorporating biosynthesized nanoparticles to carry out analogous functions. In this perspective, the major points are as follows: (i) Mitigating risk assessment factors (responsible for fate, transport, behavior, bioavailability and toxicity) for alleviating the subsequent toxicity of nanoparticles. (ii) Optimizing permissible level of nanoparticles dose within the safety limits by performing dose dependent studies. (iii) Adopting realistic approach by designing the experiments in natural habitat and avoiding in vitro assays for accurate interpretation. (iv) Most importantly, translating environmental friendly and non-toxic biosynthesized nanoparticles from laboratory to field conditions for agricultural benefits. PMID:28421100

Leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.

PubMed

Lakshmi, Bhavana Sethu; Wang, Ruobing; Madhubala, Rentala

2014-06-24

Leishmaniasis is a neglected tropical disease caused by Leishmania species. It is a major health concern affecting 88 countries and threatening 350 million people globally. Unfortunately, there are no vaccines and there are limitations associated with the current therapeutic regimens for leishmaniasis. The emerging cases of drug-resistance further aggravate the situation, demanding rapid drug and vaccine development. The genome sequence of Leishmania, provides access to novel genes that hold potential as chemotherapeutic targets or vaccine candidates. In this study, we selected 19 antigenic genes from about 8000 common Leishmania genes based on the Leishmania major and Leishmania infantum genome information available in the pathogen databases. Potential vaccine candidates thus identified were screened using an in vitro high throughput immunological platform developed in the laboratory. Four candidate genes coding for tuzin, flagellar glycoprotein-like protein (FGP), phospholipase A1-like protein (PLA1) and potassium voltage-gated channel protein (K VOLT) showed a predominant protective Th1 response over disease exacerbating Th2. We report the immunogenic properties and protective efficacy of one of the four antigens, tuzin, as a DNA vaccine against Leishmania donovani challenge. Our results show that administration of tuzin DNA protected BALB/c mice against L. donovani challenge and that protective immunity was associated with higher levels of IFN-γ and IL-12 production in comparison to IL-4 and IL-10. Our study presents a simple approach to rapidly identify potential vaccine candidates using the exhaustive information stored in the genome and an in vitro high-throughput immunological platform. Copyright © 2014. Published by Elsevier Ltd.

Surface plasmon resonance spectroscopy for characterisation of membrane protein-ligand interactions and its potential for drug discovery.

PubMed

Patching, Simon G

2014-01-01

Surface plasmon resonance (SPR) spectroscopy is a rapidly developing technique for the study of ligand binding interactions with membrane proteins, which are the major molecular targets for validated drugs and for current and foreseeable drug discovery. SPR is label-free and capable of measuring real-time quantitative binding affinities and kinetics for membrane proteins interacting with ligand molecules using relatively small quantities of materials and has potential to be medium-throughput. The conventional SPR technique requires one binding component to be immobilised on a sensor chip whilst the other binding component in solution is flowed over the sensor surface; a binding interaction is detected using an optical method that measures small changes in refractive index at the sensor surface. This review first describes the basic SPR experiment and the challenges that have to be considered for performing SPR experiments that measure membrane protein-ligand binding interactions, most importantly having the membrane protein in a lipid or detergent environment that retains its native structure and activity. It then describes a wide-range of membrane protein systems for which ligand binding interactions have been characterised using SPR, including the major drug targets G protein-coupled receptors, and how challenges have been overcome for achieving this. Finally it describes some recent advances in SPR-based technology and future potential of the technique to screen ligand binding in the discovery of drugs. This article is part of a Special Issue entitled: Structural and biophysical characterisation of membrane protein-ligand binding. Copyright © 2013 Elsevier B.V. All rights reserved.

A brief recent history of the epidemiology of congenital syphilis in the United Kingdom.

PubMed

Simms, Ian; Goh, Beng T; French, Patrick; Wallace, Lesley A; Irvine, Neil; Thomas, Daniel Rh; Winter, Andrew J; Lyall, Hermione; Webb, Sharon

2018-01-01

Within a century, congenital syphilis has been reduced from a major cause of morbidity and mortality to a condition rarely seen in the UK. Here, newly-derived literature and information searches were used to create a contemporary overview of the epidemic, including its epidemiology. Although constrained by high-quality healthcare services and with an incidence below the World Health Organization elimination threshold, congenital syphilis still has the potential to cause major consequences for the health and life chances of affected infants. If the complex challenges presented by this preventable disease are to be resolved, intervention strategies need to be optimised, rigorously assessed and extended across Europe.

Pockets of opportunity: multicultural marketing strategies for BEP growth.

PubMed

Schaefer, Kelly

2003-01-01

Ranked among the 50 largest food service corporations in America, the Randolph-Sheppard Business Enterprise Program (BEP) represents a challenging and rewarding career opportunity for Americans who are legally blind. In recent years, however, the number of facilities and facility managers has declined. Multicultural consumers represent a major emerging growth market. The multicultural market is one of the most overlooked retail markets in the United States--and the one with the most buying power and growth potential. Multicultural marketing is among the least understood strategies available to facility managers, vocational rehabilitation counselors and BEP directors. Four major minority markets are discussed and marketing strategies are offered to help BEPs target and serve these unique consumers.

Decoding genes with coexpression networks and metabolomics - 'majority report by precogs'.

PubMed

Saito, Kazuki; Hirai, Masami Y; Yonekura-Sakakibara, Keiko

2008-01-01

Following the sequencing of whole genomes of model plants, high-throughput decoding of gene function is a major challenge in modern plant biology. In view of remarkable technical advances in transcriptomics and metabolomics, integrated analysis of these 'omics' by data-mining informatics is an excellent tool for prediction and identification of gene function, particularly for genes involved in complicated metabolic pathways. The availability of Arabidopsis public transcriptome datasets containing data of >1000 microarrays reinforces the potential for prediction of gene function by transcriptome coexpression analysis. Here, we review the strategy of combining transcriptome and metabolome as a powerful technology for studying the functional genomics of model plants and also crop and medicinal plants.

Economic benefits of supersonic overland operation

NASA Technical Reports Server (NTRS)

Metwally, Munir

1992-01-01

Environmental concerns are likely to impose some restrictions on the next generation of supersonic commercial transport. There is a global concern over the effects of engine emissions on the ozone layer which protects life on Earth from ultraviolet radiation. There is also some concern over community noise. The High Speed Civil Transport (HSCT) must meet at least the current subsonic noise certification standards to be compatible with the future subsonic fleet. Concerns over sonic boom represent another environmental and marketing challenge to the HSCT program. The most attractive feature of the supersonic transport is speed, which offers the traveling public significant time-savings on long range routes. The sonic boom issue represents a major environmental and economic challenge as well. Supersonic operation overland produces the most desirable economic results. However, unacceptable overland sonic boom raise levels may force HSCT to use subsonic speeds overland. These environmental and economic challenges are likely to impose some restrictions on supersonic operation, thus introducing major changes to existing route structures and future supersonic network composition. The current subsonic route structure may have to be altered for supersonic transports to avoid sensitive areas in the stratosphere or to minimize overland flight tracks. It is important to examine the alternative route structure and the impact of these restrictions on the economic viability of the overall supersonic operation. Future market potential for HSCT fleets must be large enough to enable engine and airframe manufacturers to build the plane at a cost that provides them with an attractive return on investment and to sell it at a price that allows the airlines to operate with a reasonable margin of profit. Subsonic overland operation of a supersonic aircraft hinders its economic viability. Ways to increase the market potential of supersonic operation are described.

The lived experience of rescuing people who have driven into floodwater: Understanding challenges and identifying areas for providing support.

PubMed

Keech, Jacob J; Smith, Stephanie R; Peden, Amy E; Hagger, Martin S; Hamilton, Kyra

2018-06-11

Drowning is a major public health issue, with risk increasing during times of flood. Driving though floodwater is a major risk factor for flood-related drowning and injury, and despite widespread public health campaigns, many people continue to undertake this risky behaviour and require rescue. We aimed to identify key challenges faced by emergency services personnel when rescuing those who have driven into floodwater, and to identify strategies for supporting rescuers in this important role. Australian flood rescue operators (N=8) who had previously rescued a driver who had driven through floodwater, participated in semi-structured interviews. Data were analysed using thematic analysis. Four challenges emerged from their experiences: Involvement of untrained personnel, varying information provided by emergency telephone operators, behaviour of drivers complicating the rescue, people sightseeing floods or flood rescues, or ignoring closed roads providing sources of distraction and frustration. We propose five strategies for translating these results into practice, including: training and protocol development for (1) emergency personnel and (2) telephone operators, (3) training for rescuers regarding non-compliant rescuees, (4) educating the public, and (5) increasing compliance with closed roads. Current findings provide valuable insights into how rescuers can be supported in performing their roles, and implementation of these strategies has the potential to reduce fatalities occurring due to driving through floodwater. SO WHAT?: The strategies presented have the potential to reduce the frequency and improve the outcomes of floodwater rescues, aiding in the prevention of injury and death. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Therapeutic Genome Editing and its Potential Enhancement through CRISPR Guide RNA and Cas9 Modifications.

PubMed

Batzir, Nurit Assia; Tovin, Adi; Hendel, Ayal

2017-06-01

Genome editing with engineered nucleases is a rapidly growing field thanks to transformative technologies that allow researchers to precisely alter genomes for numerous applications including basic research, biotechnology, and human gene therapy. The genome editing process relies on creating a site-specific DNA double-strand break (DSB) by engineered nucleases and then allowing the cell's repair machinery to repair the break such that precise changes are made to the DNA sequence. The recent development of CRISPR-Cas systems as easily accessible and programmable tools for genome editing accelerates the progress towards using genome editing as a new approach to human therapeutics. Here we review how genome editing using engineered nucleases works and how using different genome editing outcomes can be used as a tool set for treating human diseases. We then review the major challenges of therapeutic genome editing and we discuss how its potential enhancement through CRISPR guide RNA and Cas9 protein modifications could resolve some of these challenges. Copyright© of YS Medical Media ltd.

Big Effect of Small Nanoparticles: A Shift in Paradigm for Polymer Nanocomposites

DOE PAGES

Cheng, Shiwang; Xie, Shi-Jie; Carrillo, Jan-Michael Y.; ...

2017-01-04

Polymer nanocomposites (PNCs) are important materials that are widely used in many current technologies and potentially have broader applications in the future due to their excellent property of tunability, light weight and low cost. But, expanding the limits in property enhancement remains a fundamental scientific challenge. We demonstrate that well-dispersed, small (diameter ~1.8 nm) nanoparticles with attractive interactions lead to unexpectedly large and qualitatively new changes in PNC structural dynamics in comparison to conventional composites based on particles of diameter ~10-50 nm. At the same time, the zero-shear viscosity at high temperatures remains comparable to that of the neat polymer,more » thereby retaining good processibility and resolving a major challenge in PNC applications. These results suggest that the nanoparticle mobility and relatively short lifetimes of nanoparticlepolymer associations open qualitatively new horizons in tunability of macroscopic properties in nanocomposites with high potential for the development of new functional materials.« less

Partnership work between Public Health and Health Psychology: introduction to a novel training programme

PubMed Central

2010-01-01

Background Public health services implement individual, community and population level interventions to change health behaviours, improve healthy life expectancy and reduce health inequalities. Understanding and changing health behaviour is complex. Integrating behaviour change theory and evidence into interventions has the potential to improve services. Methods Health Psychologists apply evidence and theories aimed at understanding and changing health behaviour. A Scottish programme is piloting the training of Health Psychologists within NHS contexts to address prominent public health challenges. Results This article outlines the details of this novel programme. Two projects are examined to illustrate the potential of partnership working between public health and health psychology. Conclusion In order to develop and improve behaviour change interventions and services, public health planners may want to consider developing and using the knowledge and skills of Health Psychologists. Supporting such training within public health contexts is a promising avenue to build critical NHS internal mass to tackle the major public health challenges ahead. PMID:21070643

Therapeutic and diagnostic challenges for frontotemporal dementia

PubMed Central

D’Alton, Simon; Lewis, Jada

2014-01-01

In the search for therapeutic modifiers, frontotemporal dementia (FTD) has traditionally been overshadowed by other conditions such as Alzheimer’s disease (AD). A clinically and pathologically diverse condition, FTD has been galvanized by a number of recent discoveries such as novel genetic variants in familial and sporadic forms of disease and the identification of TAR DNA binding protein of 43 kDa (TDP-43) as the defining constituent of inclusions in more than half of cases. In combination with an ever-expanding knowledge of the function and dysfunction of tau—a protein which is pathologically aggregated in the majority of the remaining cases—there exists a greater understanding of FTD than ever before. These advances may indicate potential approaches for the development of hypothetical therapeutics, but FTD remains highly complex and the roles of tau and TDP-43 in neurodegeneration are still wholly unclear. Here the challenges facing potential therapeutic strategies are discussed, which include sufficiently accurate disease diagnosis and sophisticated technology to deliver effective therapies. PMID:25191265

“I Need my Own Place to get Better”: Patient Perspectives on the Role of Housing in Potentially Preventable Hospitalizations

PubMed Central

Quensell, Michelle L.; Taira, Deborah A.; Seto, Todd B.; Braun, Kathryn L.; Sentell, Tetine L.

2017-01-01

Objective To analyze patient perspectives on the role of housing in their potentially preventable hospitalization. Methods Individuals admitted with cardiovascular-or diabetes-related diagnoses (n = 90) in a major medical center in Hawai‘i completed an in-person interview eliciting patient perspectives on key factors leading to hospitalization. Using the framework approach, two independent coders identified themes. This study focused on housing-related findings. Results Overall, 23% of participants reported housing as a precipitating factor to their hospitalization, including 12 with no regular place to stay. Four housing-related themes emerged: challenges meeting basic needs, complex chronic care management difficulties, stigma and relationship with provider, and stress and other mental health issues. Discussion Almost 25% of patients identified housing as a key factor to their hospital stay. Patient-reported themes highlight specific mechanisms by which housing challenges may lead to hospitalization. Addressing housing issues could help reduce the number and associated cost burden of preventable hospitalizations. PMID:28529224

Virulence Inhibitors from Brazilian Peppertree Block Quorum Sensing and Abate Dermonecrosis in Skin Infection Models

PubMed Central

Muhs, Amelia; Lyles, James T.; Parlet, Corey P.; Nelson, Kate; Kavanaugh, Jeffery S.; Horswill, Alexander R.; Quave, Cassandra L.

2017-01-01

Widespread antibiotic resistance is on the rise and current therapies are becoming increasingly limited in both scope and efficacy. Methicillin-resistant Staphylococcus aureus (MRSA) represents a major contributor to this trend. Quorum sensing controlled virulence factors include secreted toxins responsible for extensive damage to host tissues and evasion of the immune system response; they are major contributors to morbidity and mortality. Investigation of botanical folk medicines for wounds and infections led us to study Schinus terebinthifolia (Brazilian Peppertree) as a potential source of virulence inhibitors. Here, we report the inhibitory activity of a flavone rich extract “430D-F5” against all S. aureus accessory gene regulator (agr) alleles in the absence of growth inhibition. Evidence for this activity is supported by its agr-quenching activity (IC50 2–32 μg mL−1) in transcriptional reporters, direct protein outputs (α-hemolysin and δ-toxin), and an in vivo skin challenge model. Importantly, 430D-F5 was well tolerated by human keratinocytes in cell culture and mouse skin in vivo; it also demonstrated significant reduction in dermonecrosis following skin challenge with a virulent strain of MRSA. This study provides an explanation for the anti-infective activity of peppertree remedies and yields insight into the potential utility of non-biocide virulence inhibitors in treating skin infections. PMID:28186134

The importance of mass spectrometric dereplication in fungal secondary metabolite analysis

PubMed Central

Nielsen, Kristian F.; Larsen, Thomas O.

2015-01-01

Having entered the Genomic Era, it is now evident that the biosynthetic potential of filamentous fungi is much larger than was thought even a decade ago. Fungi harbor many cryptic gene clusters encoding for the biosynthesis of polyketides, non-ribosomal peptides, and terpenoids – which can all undergo extensive modifications by tailoring enzymes – thus potentially providing a large array of products from a single pathway. Elucidating the full chemical profile of a fungal species is a challenging exercise, even with elemental composition provided by high-resolution mass spectrometry (HRMS) used in combination with chemical databases (e.g., AntiBase) to dereplicate known compounds. This has led to a continuous effort to improve chromatographic separation in conjunction with improvement in HRMS detection. Major improvements have also occurred with 2D chromatography, ion-mobility, MS/MS and MS3, stable isotope labeling feeding experiments, classic UV/Vis, and especially automated data-mining and metabolomics software approaches as the sheer amount of data generated is now the major challenge. This review will focus on the development and implementation of dereplication strategies and will highlight the importance of each stage of the process from sample preparation to chromatographic separation and finally toward both manual and more targeted methods for automated dereplication of fungal natural products using state-of-the art MS instrumentation. PMID:25741325

Budding trends in integrated pest management using advanced micro- and nano-materials: Challenges and perspectives.

PubMed

Khandelwal, Neha; Barbole, Ranjit S; Banerjee, Shashwat S; Chate, Govind P; Biradar, Ankush V; Khandare, Jayant J; Giri, Ashok P

2016-12-15

One of the most vital supports to sustain human life on the planet earth is the agriculture system that has been constantly challenged in terms of yield. Crop losses due to insect pest attack even after excessive use of chemical pesticides, are major concerns for humanity and environment protection. By the virtue of unique properties possessed by micro and nano-structures, their implementation in Agri-biotechnology is largely anticipated. Hence, traditional pest management strategies are now forestalling the potential of micro and nanotechnology as an effective and viable approach to alleviate problems pertaining to pest control. These technological innovations hold promise to contribute enhanced productivity by providing novel agrochemical agents and delivery systems. Application of these systems engages to achieve: i) control release of agrochemicals, ii) site-targeted delivery of active ingredients to manage specific pests, iii) reduced pesticide use, iv) detection of chemical residues, v) pesticide degradation, vi) nucleic acid delivery and vii) to mitigate post-harvest damage. Applications of micro and nano-technology are still marginal owing to the perception of low economic returns, stringent regulatory issues involving safety assessment and public awareness over their uses. In this review, we highlight the potential application of micro and nano-materials with a major focus on effective pest management strategies including safe handling of pesticides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physics Education Research efforts to promote diversity: Challenges and opportunities

NASA Astrophysics Data System (ADS)

Brahmia, Suzanne

2015-04-01

We begin this talk with a brief description of the gender and ethnic diversity of the physics community. We then discuss several current efforts within Physics Education Research that have the potential to further our understanding of issues surrounding underrepresentation. These efforts include research into (1) the role of community and strategies for developing effective communities; (2) physics identity and self-efficacy; (3) the affordances that students from underrepresented groups bring to physics learning; (4) socioeconomics and its impact on mathematization. One of the challenges to conducting this research is the relatively small proportion of underrepresented minority students in current physics classes, and the small number of women in physics and engineering majors. In collaboration with Stephen Kanim, New Mexico State University.

Procedural Challenges In International Collaborative Research

PubMed Central

Loo, Kek Khee

2009-01-01

There is tremendous promise for a rewarding experience in an international research project due to the collaboration, mutual learning and cultural bridging that intrinsically occur. However, knowledge of the procedural requirements for international research is not widely disseminated to investigators who may not have been involved in the administration of a federal grant with a foreign component. The purpose of this article is to highlight the major challenges in administrative, procedural and equipment management aspects of grant implementation when federal funding is involved in international collaborative research. It is hoped that awareness of these difficulties and demystification of the process for future investigators can minimize the potential encumbrances in a rewarding journey towards realizing the scientific goals in an international collaborative research project. PMID:19574522

The power of sound: miniaturized medical implants with ultrasonic links

NASA Astrophysics Data System (ADS)

Wang, Max L.; Chang, Ting Chia; Charthad, Jayant; Weber, Marcus J.; Arbabian, Amin

2017-05-01

Miniaturized wirelessly powered implants capable of operating and communicating deep in the body are necessary for the next-generation of diagnostics and therapeutics. A major challenge in developing these minimally invasive implants is the tradeoff between device size, functionality, and operating depth. Here, we review two different wireless powering methods, inductive and ultrasonic power transfer, examine how to analyze their power transfer efficiency, and evaluate their potential for powering implantable medical devices. In particular, we show how ultrasonic wireless power transfer can address these challenges due to its safety, low attenuation, and millimeter wavelengths in the body. Finally, we demonstrate two ultrasonically powered implants capable of active power harvesting and bidirectional communication for closed-loop operation while functioning through multiple centimeters of tissue.

Myostatin and sarcopenia: opportunities and challenges - a mini-review.

PubMed

White, Thomas A; LeBrasseur, Nathan K

2014-01-01

The progressive loss of skeletal muscle mass, strength and/or function with advancing age, termed sarcopenia, poses a major threat to independence and quality of life. Therefore, there is significant merit in better understanding the biology of sarcopenia and developing therapeutic interventions to prevent, slow or reverse its progression. Since the discovery of myostatin, a potent negative regulator of growth that is highly enriched in skeletal muscle, there has been great interest in it as a potential mediator of sarcopenia as well as a therapeutic target. The complex biology of myostatin, the promise of myostatin inhibition as an effective means to counter sarcopenia, and the challenges facing its clinical translation are reviewed herein. © 2014 S. Karger AG, Basel.

Major Management Challenges and Program Risks: Small Business Administration

DTIC Science & Technology

2001-01-01

2001 Major Management Challenges and Program Risks Small Business AdministrationGAO-01-260 Form SF298 Citation Data Report Date ("DD MON YYYY...34) 00JAN2001 Report Type N/A Dates Covered (from... to) ("DD MON YYYY") Title and Subtitle Major Management Challenges and Program Risks Small Business ...Administration (SBA) as it seeks to aid, counsel, assist, and protect the interests of the nations small businesses and help businesses and families

rBCG30-Induced Immunity and Cross-Protection against Mycobacterium leprae Challenge Are Enhanced by Boosting with the Mycobacterium tuberculosis 30-Kilodalton Antigen 85B

PubMed Central

Gillis, Thomas P.; Tullius, Michael V.

2014-01-01

Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy. PMID:25001602

rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

PubMed

Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

2014-09-01

Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Millennium III Challenges: A Major Role for Agricultural Research/Extension/Education.

ERIC Educational Resources Information Center

National Association of State Universities and Land Grant Colleges, Washington, DC.

This report by the National Association of State Universities and Land-Grant Colleges (NASULGC) ad hoc Committee on Federal Support for Agricultural Research, Extension and Education suggests solutions to major challenges in agricultural research. Three new realities provide a powerful rationale for major new investment in agriculture: dramatic…

Major Management Challenges and Program Risks, Department of Education. Performance and Accountability Series.

ERIC Educational Resources Information Center

Comptroller General of the U.S., Washington, DC.

This report addresses the major performance and management challenges that have limited the effectiveness of the Department of Education in carrying out its mission. The booklet addresses corrective actions that Education has taken or initiated on these challenges--including a number of management initiatives to improve controls over the…

Challenge theme 5: Current and future needs of energy and mineral resources in the Borderlands and the effects of their development: Chapter 7 in United States-Mexican Borderlands: Facing tomorrow's challenges through USGS science

USGS Publications Warehouse

Updike, Randall G.; Ellis, Eugene G.; Page, William R.; Parker, Melanie J.; Hestbeck, Jay B.; Horak, William F.

2013-01-01

Exploration and extraction activities related to energy and mineral resources in the Borderlands—such as coal-fired power plants, offshore drilling, and mining—can create issues that have potentially major economic and environmental implications. Resource assessments and development projects, environmental studies, and other related evaluations help to understand some of these issues, such as power plant emissions and the erosion/denudation of abandoned mine lands. Information from predictive modeling, monitoring, and environmental assessments are necessary to understand the full effects of energy and mineral exploration, development, and utilization. The exploitation of these resources can negatively affect human health and the environment, its natural resources, and its ecological services (air, water, soil, recreation, wildlife, etc.). This chapter describes the major energy and mineral issues of the Borderlands and how geologic frameworks, integrated interdisciplinary (geobiologic) investigations, and other related studies can address the anticipated increases in demands on natural resources in the region.

Evaluating the Benefits of Adaptation of Critical Infrastructures to Hydrometeorological Risks.

PubMed

Thacker, Scott; Kelly, Scott; Pant, Raghav; Hall, Jim W

2018-01-01

Infrastructure adaptation measures provide a practical way to reduce the risk from extreme hydrometeorological hazards, such as floods and windstorms. The benefit of adapting infrastructure assets is evaluated as the reduction in risk relative to the "do nothing" case. However, evaluating the full benefits of risk reduction is challenging because of the complexity of the systems, the scarcity of data, and the uncertainty of future climatic changes. We address this challenge by integrating methods from the study of climate adaptation, infrastructure systems, and complex networks. In doing so, we outline an infrastructure risk assessment that incorporates interdependence, user demands, and potential failure-related economic losses. Individual infrastructure assets are intersected with probabilistic hazard maps to calculate expected annual damages. Protection measure costs are integrated to calculate risk reduction and associated discounted benefits, which are used to explore the business case for investment in adaptation. A demonstration of the methodology is provided for flood protection of major electricity substations in England and Wales. We conclude that the ongoing adaptation program for major electricity assets is highly cost beneficial. © 2017 Society for Risk Analysis.

Addressing Medicaid/marketplace churn through multimarket plans: assessing the current state of play.

PubMed

Rosenbaum, Sara

2015-02-01

Both before and after the Affordable Care Act (ACA), the US health insurance system is characterized by fragmentation. Pre-ACA, this fragmentation included major coverage gaps, causing significant periods of coverage interruption, especially for lower-income people. The ACA does not end the problem of churning among sources of public financing, but it does hold the potential for enabling people to move among sources of coverage rather than go without insurance. Several strategies for reducing coverage churn exist, but none is foolproof and all are in their early stages. Thus the ability of issuers to participate across multiple public financing arrangements and to offer stable provider networks becomes crucial to achieving continuity of care. Interviews with nine companies involved in developing or operating multimarket strategies confirm the feasibility of this approach while revealing major challenges, especially the challenge of finding providers willing to treat members regardless of the source of coverage. Strategies for increasing multimarket plans and networks represent one of the great areas of future policy and operational focus. Copyright © 2015 by Duke University Press.

Design and Development of Microsomal Prostaglandin E2 Synthase-1 Inhibitors: Challenges and Future Directions.

PubMed

Koeberle, Andreas; Laufer, Stefan A; Werz, Oliver

2016-07-14

Microsomal prostaglandin E2 synthase (mPGES)-1 is responsible for the massive prostaglandin E2 (PGE2) formation during inflammation. Increasing evidence reveals mPGES-1 inhibitors as a safe alternative to nonsteroidal anti-inflammatory drugs. The first selective mPGES-1 inhibitors recently entered clinical trials. Major challenges for drug development have been the high plasma protein binding of lead structures, interspecies discrepancies, nuisance inhibition, sophisticated enzyme assays, and limited structural information about the mPGES-1 inhibitor binding site. Since most of these drawbacks could be solved during the past few years, we are standing at the threshold of a new era of mPGES-1-targeting anti-inflammatory drugs. This perspective introduces mPGES-1 as a key player within the network of eicosanoid biosynthesis and summarizes our current understanding of its structure and mechanism. Moreover, we present high-throughput and in silico screening techniques and discuss the structure-activity relationship and pharmacological potential of major mPGES-1 inhibitor classes in light of recent insights from pharmacophore models and cocrystallization studies.

Challenges and opportunities of airborne metagenomics.

PubMed

Behzad, Hayedeh; Gojobori, Takashi; Mineta, Katsuhiko

2015-05-06

Recent metagenomic studies of environments, such as marine and soil, have significantly enhanced our understanding of the diverse microbial communities living in these habitats and their essential roles in sustaining vast ecosystems. The increase in the number of publications related to soil and marine metagenomics is in sharp contrast to those of air, yet airborne microbes are thought to have significant impacts on many aspects of our lives from their potential roles in atmospheric events such as cloud formation, precipitation, and atmospheric chemistry to their major impact on human health. In this review, we will discuss the current progress in airborne metagenomics, with a special focus on exploring the challenges and opportunities of undertaking such studies. The main challenges of conducting metagenomic studies of airborne microbes are as follows: 1) Low density of microorganisms in the air, 2) efficient retrieval of microorganisms from the air, 3) variability in airborne microbial community composition, 4) the lack of standardized protocols and methodologies, and 5) DNA sequencing and bioinformatics-related challenges. Overcoming these challenges could provide the groundwork for comprehensive analysis of airborne microbes and their potential impact on the atmosphere, global climate, and our health. Metagenomic studies offer a unique opportunity to examine viral and bacterial diversity in the air and monitor their spread locally or across the globe, including threats from pathogenic microorganisms. Airborne metagenomic studies could also lead to discoveries of novel genes and metabolic pathways relevant to meteorological and industrial applications, environmental bioremediation, and biogeochemical cycles. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Immunization with Live Human Rhinovirus (HRV) 16 Induces Protection in Cotton Rats against HRV14 Infection

PubMed Central

Patel, Mira C.; Pletneva, Lioubov M.; Boukhvalova, Marina S.; Vogel, Stefanie N.; Kajon, Adriana E.; Blanco, Jorge C. G.

2017-01-01

Human rhinoviruses (HRVs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against HRVs are available to prevent or mitigate HRV infection. There are more than 150 antigenically heterogeneous HRV serotypes, with ∼90 HRVs belonging to major group species A and B. Development of small animal models that are susceptible to infection with major group HRVs would be beneficial for vaccine research. Previously, we showed that the cotton rat (Sigmodon hispidus) is semi-permissive to HRV16 (major group, species HRV-A virus) infection, replicating in the upper and lower respiratory tracts with measurable pathology, mucus production, and expression of inflammatory mediators. Herein, we report that intranasal infection of cotton rats with HRV14 (major group, species HRV-B virus) results in isolation of infectious virus from the nose and lung. Similar to HRV16, intramuscular immunization with live HRV14 induces homologous protection that correlated with high levels of serum neutralizing antibodies. Vaccination and challenge experiments with HRV14 and HRV16 to evaluate the development of cross-protective immunity demonstrate that intramuscular immunization with live HRV16 significantly protects animals against HRV14 challenge. Determination of the immunological mechanisms involved in heterologous protection and further characterization of infection with other major HRV serotypes in the cotton rat could enhance the robustness of the model to define heterotypic relationships between this diverse group of viruses and thereby increase its potential for development of a multi-serotype HRV vaccine. PMID:28912760

Chemical genetics and its potential in cardiac stem cell therapy

PubMed Central

Vieira, Joaquim M; Riley, Paul R

2013-01-01

Over the last decade or so, intensive research in cardiac stem cell biology has led to significant discoveries towards a potential therapy for cardiovascular disease; the main cause of morbidity and mortality in humans. The major goal within the field of cardiovascular regenerative medicine is to replace lost or damaged cardiac muscle and coronaries following ischaemic disease. At present, de novo cardiomyocytes can be generated either in vitro, for cell transplantation or disease modelling using directed differentiation of embryonic stem cells or induced pluripotent stem cells, or in vivo via direct reprogramming of resident adult cardiac fibroblast or ectopic stimulation of resident cardiac stem or progenitor cells. A major bottleneck with all of these approaches is the low efficiency of cardiomyocyte differentiation alongside their relative functional immaturity. Chemical genetics, and the application of phenotypic screening with small molecule libraries, represent a means to enhance understanding of the molecular pathways controlling cardiovascular cell differentiation and, moreover, offer the potential for discovery of new drugs to invoke heart repair and regeneration. Here, we review the potential of chemical genetics in cardiac stem cell therapy, highlighting not only the major contributions to the field so far, but also the future challenges. LINKED ARTICLES This article is part of a themed section on Regenerative Medicine and Pharmacology: A Look to the Future. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-2 PMID:22385148

Making capitated Medicare work for women: policy and research challenges.

PubMed

Bierman, A S; Clancy, C M

2000-01-01

Growth in capitated Medicare has special ramifications for older women who comprise the majority of Medicare beneficiaries. Older women are more likely than men to have chronic conditions that lead to illness and disability, and they often have fewer financial and social resources to cope with these problems. Gender differences in health status have a number of important implications for the financing and delivery of care for older women under both traditional fee-for-service Medicare and capitation. The utilization of effective preventive interventions, new therapeutic interventions for the management of common chronic disorders, and more cost-effective models of chronic disease management could potentially extend the active life expectancy of older women. However, there are financial and delivery system barriers to achieving these objectives. Traditional FFS Medicare has gaps in coverage of care for chronic illness and disability that disproportionately impact women. Managed care potentially offers flexibility to allocate resources creatively, to develop new models of care, and offer enhanced benefits with lower out-of-pocket costs. However, challenges to realizing this potential under Medicare managed care with unique implications for older women include: possible gender bias in capitation payments, risk selection, inadequacy of risk adjustment models, benefit and market instability, and disenrollment patterns.

Safety of disease-modifying drugs for multiple sclerosis in pregnancy: current challenges and future considerations for effective pharmacovigilance.

PubMed

Lu, Ellen; Wang, Bing Wei; Guimond, Colleen; Synnes, Anne; Sadovnick, A Dessa; Dahlgren, Leanne; Traboulsee, Anthony; Tremlett, Helen

2013-03-01

When contemplating a pregnancy, women treated for multiple sclerosis (MS) with a disease-modifying drug must decide to discontinue their medication before conception or risk exposing their unborn child to potential drug toxicity. Few studies exist as reference for patients and physicians, and of those available, the majority are less than ideal due to real-world constraints, ethical issues and methodological shortcomings. The authors provide a brief summary of existing animal and human data with current recommendations regarding the safety of IFN-β, glatiramer acetate, natalizumab, mitoxantrone, fingolimod and teriflunomide during pregnancy and lactation in women with MS. We also assess the quality, strengths and limitations of the existing studies including challenges with study design. The investigation of outcomes such as spontaneous abortion and congenital anomalies are highlighted with potential methodological improvements for future studies on drug safety in pregnancy suggested. The authors explore the pharmacokinetics and pharmacodynamics of the MS disease-modifying drugs for their possible mechanistic role in fetal harm and discuss the potential role of clinical trials. Future pharmacovigilance studies should continue to pursue multicenter collaboration with an emphasis on appropriate study design.

Bio-analytical applications of microbial fuel cell-based biosensors for onsite water quality monitoring.

PubMed

ElMekawy, A; Hegab, H M; Pant, D; Saint, C P

2018-01-01

Globally, sustainable provision of high-quality safe water is a major challenge of the 21st century. Various chemical and biological monitoring analytics are presently utilized to guarantee the availability of high-quality water. However, these techniques still face some challenges including high costs, complex design and onsite and online limitations. The recent technology of using microbial fuel cell (MFC)-based biosensors holds outstanding potential for the rapid and real-time monitoring of water source quality. MFCs have the advantages of simplicity in design and efficiency for onsite sensing. Even though some sensing applications of MFCs were previously studied, e.g. biochemical oxygen demand sensor, recently numerous research groups around the world have presented new practical applications of this technique, which combine multidisciplinary scientific knowledge in materials science, microbiology and electrochemistry fields. This review presents the most updated research on the utilization of MFCs as potential biosensors for monitoring water quality and considers the range of potentially toxic analytes that have so far been detected using this methodology. The advantages of MFCs over established technology are also considered as well as future work required to establish their routine use. © 2017 The Society for Applied Microbiology.

Graphene and the immune system: Challenges and potentiality.

PubMed

Orecchioni, Marco; Ménard-Moyon, Cécilia; Delogu, Lucia Gemma; Bianco, Alberto

2016-10-01

In the growing area of nanomedicine, graphene-based materials (GBMs) are some of the most recent explored nanomaterials. For the majority of GBM applications in nanomedicine, the immune system plays a fundamental role. It is necessary to well understand the complexity of the interactions between GBMs, the immune cells, and the immune components and how they could be of advantage for novel effective diagnostic and therapeutic approaches. In this review, we aimed at painting the current picture of GBMs in the background of the immune system. The picture we have drawn looks like a cubist image, a sort of Picasso-like portrait looking at the topic from all perspectives: the challenges (due to the potential toxicity) and the potentiality like the conjugation of GBMs to biomolecules to develop advanced nanomedicine tools. In this context, we have described and discussed i) the impact of graphene on immune cells, ii) graphene as immunobiosensor, and iii) antibodies conjugated to graphene for tumor targeting. Thanks to the huge advances on graphene research, it seems realistic to hypothesize in the near future that some graphene immunoconjugates, endowed of defined immune properties, can go through preclinical test and be successfully used in nanomedicine. Copyright © 2016 Elsevier B.V. All rights reserved.

One Health contributions towards more effective and equitable approaches to health in low- and middle-income countries

PubMed Central

Sharp, J.; Abela-Ridder, B.; Allan, K. J.; Buza, J.; Crump, J. A.; Davis, A.; Del Rio Vilas, V. J.; de Glanville, W. A.; Kazwala, R. R.; Kibona, T.; Lankester, F. J.; Lugelo, A.; Mmbaga, B. T.; Rubach, M. P.; Swai, E. S.; Waldman, L.; Haydon, D. T.; Hampson, K.

2017-01-01

Emerging zoonoses with pandemic potential are a stated priority for the global health security agenda, but endemic zoonoses also have a major societal impact in low-resource settings. Although many endemic zoonoses can be treated, timely diagnosis and appropriate clinical management of human cases is often challenging. Preventive ‘One Health’ interventions, e.g. interventions in animal populations that generate human health benefits, may provide a useful approach to overcoming some of these challenges. Effective strategies, such as animal vaccination, already exist for the prevention, control and elimination of many endemic zoonoses, including rabies, and several livestock zoonoses (e.g. brucellosis, leptospirosis, Q fever) that are important causes of human febrile illness and livestock productivity losses in low- and middle-income countries. We make the case that, for these diseases, One Health interventions have the potential to be more effective and generate more equitable benefits for human health and livelihoods, particularly in rural areas, than approaches that rely exclusively on treatment of human cases. We hypothesize that applying One Health interventions to tackle these health challenges will help to build trust, community engagement and cross-sectoral collaboration, which will in turn strengthen the capacity of fragile health systems to respond to the threat of emerging zoonoses and other future health challenges. One Health interventions thus have the potential to align the ongoing needs of disadvantaged communities with the concerns of the broader global community, providing a pragmatic and equitable approach to meeting the global goals for sustainable development and supporting the global health security agenda. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’. PMID:28584176

RecA: a universal drug target in pathogenic bacteria.

PubMed

Pavlopoulou, Athanasia

2018-01-01

The spread of bacterial infectious diseases due to the development of resistance to antibiotic drugs in pathogenic bacteria is an emerging global concern. Therefore, the efficacious management and prevention of bacterial infections are major public health challenges. RecA is a pleiotropic recombinase protein that has been demonstrated to be implicated strongly in the bacterial drug resistance, survival and pathogenicity. In this minireview, RecA's role in the development of antibiotic resistance and its potential as an antimicrobial drug target are discussed.

Attending to the forest and the trees. Reply to comments on “Toward a computational framework for cognitive biology: Unifying approaches from cognitive neuroscience and comparative cognition”

NASA Astrophysics Data System (ADS)

Fitch, W. Tecumseh

2014-09-01

I am grateful to the commentators for their kind and generally positive comments, and the many interesting and challenging remarks and observations. While limitations of space and time preclude me pursuing each of the interesting lines of potential discussion or debate opened up by these commentaries, I will try to respond to all of the major points, roughly following the original order of the target article [1].

Adapting the SERVQUAL scale to hospital services: an empirical investigation.

PubMed Central

Babakus, E; Mangold, W G

1992-01-01

Defining and measuring the quality of service has been a major challenge for health care marketers. A comprehensive service quality measurement scale (SERVQUAL) is empirically evaluated for its potential usefulness in a hospital service environment. Active participation by hospital management helped to address practical and user-related aspects of the assessment. The completed expectations and perceptions scales met various criteria for reliability and validity. Suggestions are provided for the managerial use of the scale, and a number of future research issues are identified. PMID:1737708

The Grand Challenges of Organ Banking: Proceedings from the first global summit on complex tissue cryopreservation.

PubMed

Lewis, Jedediah K; Bischof, John C; Braslavsky, Ido; Brockbank, Kelvin G M; Fahy, Gregory M; Fuller, Barry J; Rabin, Yoed; Tocchio, Alessandro; Woods, Erik J; Wowk, Brian G; Acker, Jason P; Giwa, Sebastian

2016-04-01

The first Organ Banking Summit was convened from Feb. 27 - March 1, 2015 in Palo Alto, CA, with events at Stanford University, NASA Research Park, and Lawrence Berkeley National Labs. Experts at the summit outlined the potential public health impact of organ banking, discussed the major remaining scientific challenges that need to be overcome in order to bank organs, and identified key opportunities to accelerate progress toward this goal. Many areas of public health could be revolutionized by the banking of organs and other complex tissues, including transplantation, oncofertility, tissue engineering, trauma medicine and emergency preparedness, basic biomedical research and drug discovery - and even space travel. Key remaining scientific sub-challenges were discussed including ice nucleation and growth, cryoprotectant and osmotic toxicities, chilling injury, thermo-mechanical stress, the need for rapid and uniform rewarming, and ischemia/reperfusion injury. A variety of opportunities to overcome these challenge areas were discussed, i.e. preconditioning for enhanced stress tolerance, nanoparticle rewarming, cyroprotectant screening strategies, and the use of cryoprotectant cocktails including ice binding agents. Copyright © 2015.

The environment as radical politics: Can ?Third World? education rise to the challenge?

NASA Astrophysics Data System (ADS)

Hickling-Hudson, Anne

1994-01-01

The pattern of industrial development which has been adopted globally in the last two centuries by both capitalist and socialist economies has caused unprecedented damage to the physical and ecological health of our planet. This paper argues that any challenges to these systems, including educational challenges, will involve political understanding and activism. It examines the potential of educational structures in Third World regions, using the Caribbean as the main example, for implementing eco-political education. This would involve encouraging students to use ecological and social justice criteria for comparing consumerist with sustainable development approaches to rethinking and refashioning the international economy, particularly the Third World share of it. It would involve teachers and students exploring how political and economic structures could be challenged and altered to obtain a fairer quality of life for the majorities now living in poverty and an adjustment of the opulent and wasteful lifestyles of affluent minorities primarily responsible for environmental degradation. Finally, those in eco-political education would work to achieve such goals within broad movements and pressure groups in rich and poor countries.

Implementation of the Integrated Management of Childhood Illnesses strategy: challenges and recommendations in Botswana.

PubMed

Mupara, Lucia U; Lubbe, Johanna C

2016-01-01

Under-five mortality has been a major public health challenge from time immemorial. In response to this challenge, the World Health Organization and the United Nations Children's Fund developed the Integrated Management of Childhood Illnesses (IMCI) strategy and presented it to the whole world as a key approach to reduce child morbidity and mortality. Botswana started to implement the IMCI strategy in 1998. Reductions in the under-five mortality rate (U5MR) have been documented, although the reduction is not on par with the expected Millennium Development Goal 4 predictions. A quantitative study was done to identify the problems IMCI implementers face when tending children under 5 years in the Gaborone Health District of Botswana. The study population was made up of all the IMCI-trained and registered nurses, and systematic sampling was used to randomly select study participants. Questionnaires were used to collect data. The study findings indicated challenges related to low training coverage, health systems, and the unique features of the IMCI strategy. The comprehensive implementation of the IMCI strategy has the potential to significantly influence the U5MR in Botswana.

Motivators for Alzheimer's disease clinical trial participation.

PubMed

Bardach, Shoshana H; Holmes, Sarah D; Jicha, Gregory A

2018-02-01

Alzheimer's disease (AD) research progress is impeded due to participant recruitment challenges. This study seeks to better understand, from the perspective of individuals engaged in clinical trials (CTs), research motivations. Participants, or their caregivers, from AD treatment and prevention CTs were surveyed about research motivators. The 87 respondents had a mean age of 72.2, were predominantly Caucasian, 55.2% were male, and 56.3% had cognitive impairment. An overwhelming majority rated the potential to help themselves or a loved one and the potential to help others in the future as important motivators. Relatively few respondents were motivated by free healthcare, monetary rewards, or to make others happy. Recruitment efforts should focus on the potential benefit for the individual, their loved ones, and others in the future rather than free healthcare or monetary rewards.

Food Security Under Shifting Economic, Demographic, and Climatic Conditions (Invited)

NASA Astrophysics Data System (ADS)

Naylor, R. L.

2013-12-01

Global demand for food, feed, and fuel will continue to rise in a more populous and affluent world. Meeting this demand in the future will become increasingly challenging with global climate change; when production shocks stemming from climate variability are added to the new mean climate state, food markets could become more volatile. This talk will focus on the interacting market effects of demand and supply for major food commodities, with an eye on climate-related supply trends and shocks. Lessons from historical patterns of climate variability (e.g., ENSO and its global teleconnections) will be used to infer potential food security outcomes in the event of abrupt changes in the mean climate state. Domestic food and trade policy responses to crop output and price volatility in key producing and consuming nations, such as export bans and import tariffs, will be discussed as a potentially major destabilizing force, underscoring the important influence of uncertainty in achieving--or failing to achieve--food security.

Landowner and practitioner perspectives on private land conservation programs

USGS Publications Warehouse

Lute, Michelle L.; Gillespie, Caitlyn R.; Fontaine, Joseph J.; Martin, Dustin R.

2018-01-01

Efforts to reverse declines in native grasslands benefit from agricultural policies that encourage private land conservation. The U.S. Department of Agriculture’s Conservation Reserve Program (CRP) improved conservation across landscapes but enrollment has declined. We used sequential exploratory mixed methods to compare landowner and conservation practitioners’ perceptions, evaluate perceived benefits, and identify potential improvements to CRP. Focus groups of practitioners informed a quantitative survey of landowners who had properties >160 total acres in Nebraska. Results suggest potential misalignment in perceptions between practitioners and landowners. Practitioners were concerned that conservation, especially of wildlife, was secondary to profit. But the majority of landowners valued CRP-related ecosystem services, including native pollinators. Practitioners posited that younger landowners were primarily profit motivated, but CRP enrollment did not differ by demographics. Practitioners and landowners identified rule complexity as a major challenge and practitioner–landowner relationships as critical to success. Findings suggest that practitioners may underestimate non-economic motivations and illuminate opportunities to encourage private land conservation.

(Re-)programming of subtype specific cardiomyocytes.

PubMed

Hausburg, Frauke; Jung, Julia Jeannine; Hoch, Matti; Wolfien, Markus; Yavari, Arash; Rimmbach, Christian; David, Robert

2017-10-01

Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential - a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterized by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production. In addition, the recent achievement of directly reprogramming somatic cells into cardiomyocytes is likely to become of great importance. In either case, different clinical scenarios will require the generation of highly pure, specific cardiac cellular-subtypes. In this review, we discuss these themes as related to the cardiovascular stem cell and programming field, including a focus on the emergent topic of pacemaker cell generation for the development of biological pacemakers and in vitro drug testing. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience

PubMed Central

Huffman, Derek M.; Justice, Jamie N.; Stout, Michael B.; Kirkland, James L.; Barzilai, Nir

2016-01-01

Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains. A particularly sensitive metric of health is the ability to respond to, and recover, from stress. Therefore, the Network also considered stresses of human relevance that could be implemented in mouse models to assess frailty and resilience. Mouse models already exist for responses to forced immobility, cancer chemotherapy, infectious diseases, dietary challenges, and surgical stress, and it was felt that these could be employed to determine whether putative senescence-retarding interventions increased and extended organismal robustness. The Network discussed challenges in modeling age-related human chronic diseases and concluded that more attention needs to be paid to developing disease models with later age of onset, models of co- and multimorbidity, diversifying the strains and sexes commonly used in aging research, and considering additional species. PMID:27535967

Key enzymes and proteins of crop insects as candidate for RNAi based gene silencing

PubMed Central

Kola, Vijaya Sudhakara Rao; Renuka, P.; Madhav, Maganti Sheshu; Mangrauthia, Satendra K.

2015-01-01

RNA interference (RNAi) is a mechanism of homology dependent gene silencing present in plants and animals. It operates through 21–24 nucleotides small RNAs which are processed through a set of core enzymatic machinery that involves Dicer and Argonaute proteins. In recent past, the technology has been well appreciated toward the control of plant pathogens and insects through suppression of key genes/proteins of infecting organisms. The genes encoding key enzymes/proteins with the great potential for developing an effective insect control by RNAi approach are actylcholinesterase, cytochrome P450 enzymes, amino peptidase N, allatostatin, allatotropin, tryptophan oxygenase, arginine kinase, vacuolar ATPase, chitin synthase, glutathione-S-transferase, catalase, trehalose phosphate synthase, vitellogenin, hydroxy-3-methylglutaryl coenzyme A reductase, and hormone receptor genes. Through various studies, it is demonstrated that RNAi is a reliable molecular tool which offers great promises in meeting the challenges imposed by crop insects with careful selection of key enzymes/proteins. Utilization of RNAi tool to target some of these key proteins of crop insects through various approaches is described here. The major challenges of RNAi based insect control such as identifying potential targets, delivery methods of silencing trigger, off target effects, and complexity of insect biology are very well illustrated. Further, required efforts to address these challenges are also discussed. PMID:25954206

The Adverse Drug Reactions from Patient Reports in Social Media Project: Five Major Challenges to Overcome to Operationalize Analysis and Efficiently Support Pharmacovigilance Process.

PubMed

Bousquet, Cedric; Dahamna, Badisse; Guillemin-Lanne, Sylvie; Darmoni, Stefan J; Faviez, Carole; Huot, Charles; Katsahian, Sandrine; Leroux, Vincent; Pereira, Suzanne; Richard, Christophe; Schück, Stéphane; Souvignet, Julien; Lillo-Le Louët, Agnès; Texier, Nathalie

2017-09-21

Adverse drug reactions (ADRs) are an important cause of morbidity and mortality. Classical Pharmacovigilance process is limited by underreporting which justifies the current interest in new knowledge sources such as social media. The Adverse Drug Reactions from Patient Reports in Social Media (ADR-PRISM) project aims to extract ADRs reported by patients in these media. We identified 5 major challenges to overcome to operationalize the analysis of patient posts: (1) variable quality of information on social media, (2) guarantee of data privacy, (3) response to pharmacovigilance expert expectations, (4) identification of relevant information within Web pages, and (5) robust and evolutive architecture. This article aims to describe the current state of advancement of the ADR-PRISM project by focusing on the solutions we have chosen to address these 5 major challenges. In this article, we propose methods and describe the advancement of this project on several aspects: (1) a quality driven approach for selecting relevant social media for the extraction of knowledge on potential ADRs, (2) an assessment of ethical issues and French regulation for the analysis of data on social media, (3) an analysis of pharmacovigilance expert requirements when reviewing patient posts on the Internet, (4) an extraction method based on natural language processing, pattern based matching, and selection of relevant medical concepts in reference terminologies, and (5) specifications of a component-based architecture for the monitoring system. Considering the 5 major challenges, we (1) selected a set of 21 validated criteria for selecting social media to support the extraction of potential ADRs, (2) proposed solutions to guarantee data privacy of patients posting on Internet, (3) took into account pharmacovigilance expert requirements with use case diagrams and scenarios, (4) built domain-specific knowledge resources embeding a lexicon, morphological rules, context rules, semantic rules, syntactic rules, and post-analysis processing, and (5) proposed a component-based architecture that allows storage of big data and accessibility to third-party applications through Web services. We demonstrated the feasibility of implementing a component-based architecture that allows collection of patient posts on the Internet, near real-time processing of those posts including annotation, and storage in big data structures. In the next steps, we will evaluate the posts identified by the system in social media to clarify the interest and relevance of such approach to improve conventional pharmacovigilance processes based on spontaneous reporting. ©Cedric Bousquet, Badisse Dahamna, Sylvie Guillemin-Lanne, Stefan J Darmoni, Carole Faviez, Charles Huot, Sandrine Katsahian, Vincent Leroux, Suzanne Pereira, Christophe Richard, Stéphane Schück, Julien Souvignet, Agnès Lillo-Le Louët, Nathalie Texier. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 21.09.2017.

Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

PubMed Central

Mamo, Tewodros; Moseman, E Ashley; Kolishetti, Nagesh; Salvador-Morales, Carolina; Shi, Jinjun; Kuritzkes, Daniel R; Langer, Robert; von Andrian, Ulrich

2010-01-01

Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides. PMID:20148638

Autophagy-Inflammasome Interplay in Heart Failure: A Systematic Review on Basics, Pathways, and Therapeutic Perspectives.

PubMed

Chiu, Bonnie; Jantuan, Eugeniu; Shen, Fan; Chiu, Brian; Sergi, Consolato

2017-05-01

Aging of the population contributes to the increasing prevalence of heart failure. Autophagy is an evolutionarily conserved process aiming to degrade both long-lived proteins and damaged or excessive cyto-organelles via the lysosomal-mediated pathway. Although autophagy is involved in the normal homeostasis of cardiovascular cells, upregulation of autophagy and its abnormal modulation by inflammation may lead to cardiovascular functional decline and heart failure. Despite major improvements in the prevention, diagnosis, and treatment of cardiovascular diseases, heart failure remains one of the major diagnostic and therapeutic challenges. Here, we review the cardiovascular autophagy and its interplay with inflammation which may lead to heart failure exploring some potential treatment options. © 2017 by the Association of Clinical Scientists, Inc.

Medical journal peer review: process and bias.

PubMed

Manchikanti, Laxmaiah; Kaye, Alan D; Boswell, Mark V; Hirsch, Joshua A

2015-01-01

Scientific peer review is pivotal in health care research in that it facilitates the evaluation of findings for competence, significance, and originality by qualified experts. While the origins of peer review can be traced to the societies of the eighteenth century, it became an institutionalized part of the scholarly process in the latter half of the twentieth century. This was a response to the growth of research and greater subject specialization. With the current increase in the number of specialty journals, the peer review process continues to evolve to meet the needs of patients, clinicians, and policy makers. The peer review process itself faces challenges. Unblinded peer review might suffer from positive or negative bias towards certain authors, specialties, and institutions. Peer review can also suffer when editors and/or reviewers might be unable to understand the contents of the submitted manuscript. This can result in an inability to detect major flaws, or revelations of major flaws after acceptance of publication by the editors. Other concerns include potentially long delays in publication and challenges uncovering plagiarism, duplication, corruption and scientific misconduct. Conversely, a multitude of these challenges have led to claims of scientific misconduct and an erosion of faith. These challenges have invited criticism of the peer review process itself. However, despite its imperfections, the peer review process enjoys widespread support in the scientific community. Peer review bias is one of the major focuses of today's scientific assessment of the literature. Various types of peer review bias include content-based bias, confirmation bias, bias due to conservatism, bias against interdisciplinary research, publication bias, and the bias of conflicts of interest. Consequently, peer review would benefit from various changes and improvements with appropriate training of reviewers to provide quality reviews to maintain the quality and integrity of research without bias. Thus, an appropriate, transparent peer review is not only ideal, but necessary for the future to facilitate scientific progress.

Cold-water coral carbonate mounds as unique palaeo-archives: the Plio-Pleistocene Challenger Mound record (NE Atlantic)

NASA Astrophysics Data System (ADS)

Thierens, M.; Browning, E.; Pirlet, H.; Loutre, M.-F.; Dorschel, B.; Huvenne, V. A. I.; Titschack, J.; Colin, C.; Foubert, A.; Wheeler, A. J.

2013-08-01

Through the interplay of a stabilising cold-water coral framework and a dynamic sedimentary environment, cold-water coral carbonate mounds create distinctive centres of bio-geological accumulation in often complex (continental margin) settings. The IODP Expedition 307 drilling of the Challenger Mound (eastern Porcupine Seabight; NE Atlantic) not only retrieved the first complete developmental history of a coral carbonate mound, it also exposed a unique, Early-Pleistocene sedimentary sequence of exceptional resolution along the mid-latitudinal NE Atlantic margin. In this study, a comprehensive assessment of the Challenger Mound as an archive of Quaternary palaeo-environmental change and long-term coral carbonate mound development is presented. New and existing environmental proxy records, including clay mineralogy, planktonic foraminifer and calcareous nannofossil biostratigraphy and assemblage counts, planktonic foraminifer oxygen isotopes and siliciclastic particle-size, are thereby discussed within a refined chronostratigraphic and climatic context. Overall, the development of the Challenger Mound shows a strong affinity to the Plio-Pleistocene evolution of the Northern Hemisphere climate system, albeit not being completely in phase with it. The two major oceanographic and climatic transitions of the Plio-Pleistocene - the Late Pliocene/Early Pleistocene intensification of continental ice-sheet development and the mid-Pleistocene transition to the more extremely variable and more extensively glaciated late Quaternary - mark two major thresholds in Challenger Mound development: its Late Pliocene (>2.74 Ma) origin and its Middle-Late Pleistocene to recent decline. Distinct surface-water perturbations (i.e. water-mass/polar front migrations, productivity changes, melt-water pulses) are identified throughout the sequence, which can be linked to the intensity and extent of ice development on the nearby British-Irish Isles since the earliest Pleistocene. Glaciation-induced shifts in surface-water primary productivity are thereby proposed to fundamentally control cold-water coral growth, which in turn influences on-mound sediment accumulation and, hence, coral carbonate mound development throughout the Pleistocene. As local factors, such as proximal ice-sheet dynamics and on-mound changes in cold-water coral density, significantly affected the development of the Challenger Mound, they can potentially explain the nature of its palaeo-record and its offsets with the periodicities of global climate variability. On the other hand, owing to this unique setting, a regionally exceptional, high-resolution palaeo-record of Early Pleistocene (ca 2.6 to 2.1 Ma) environmental change (including early British-Irish ice-sheet development), broadly in phase with the 41 ka-paced global climate system, is preserved in the lower Challenger Mound. All in all, the Challenger Mound record highlights the wider relevance of coral carbonate mound archives and their potential to capture unique records from dynamic (continental margin) environments.

Non-governmental organizations in international health: past successes, future challenges.

PubMed

Gellert, G A

1996-01-01

Non-governmental organizations, or NGOs, are increasingly instrumental to the implementation of international health programs. Following an overview of current conditions in global health and the problems that could be targeted by NGOs, this article describes the activities and philosophies of several representative approaches in this sector. The attributes of NGOs that increase their potential effectiveness are discussed, including ability to reach areas of severe need, promotion of local involvement, low cost of operations, adaptiveness and innovation, independence, and sustainability. A summary is provided of major future challenges in international health that may be addressed by NGOs, with particular emphasis on tobacco-related disease, communicable diseases and the AIDS epidemic, maternal mortality and women's health, injury prevention and control, and the need to secure durable financial support.

Future implications of eHealth interventions for chronic pain management in underserved populations.

PubMed

DeMonte, Colette M; DeMonte, William D; Thorn, Beverly E

2015-01-01

Many underserved communities, especially those in rural settings, face unique challenges that make high quality healthcare less accessible. The implementation of eHealth technologies has become a potentially valuable option to disseminate interventions. The authors' work in rural Alabama Federally Qualified Health Centers provide insights into the access to technology as well as the likelihood of utilizing eHealth technology in underserved communities. This paper will review current challenges related to digital dissemination of behavioral health interventions for chronic pain. Two major concerns are the lack of technological resources and the lack of appropriate materials for patients who may have low levels of reading, health and/or digital literacy. We will propose some recommendations to address common barriers faced by those providing care.

The challenge of education and learning in the developing world.

PubMed

Kremer, Michael; Brannen, Conner; Glennerster, Rachel

2013-04-19

Across many different contexts, randomized evaluations find that school participation is sensitive to costs: Reducing out-of-pocket costs, merit scholarships, and conditional cash transfers all increase schooling. Addressing child health and providing information on how earnings rise with education can increase schooling even more cost-effectively. However, among those in school, test scores are remarkably low and unresponsive to more-of-the-same inputs, such as hiring additional teachers, buying more textbooks, or providing flexible grants. In contrast, pedagogical reforms that match teaching to students' learning levels are highly cost effective at increasing learning, as are reforms that improve accountability and incentives, such as local hiring of teachers on short-term contracts. Technology could potentially improve pedagogy and accountability. Improving pre- and postprimary education are major future challenges.

Traditional use and management of NTFPs in Kangchenjunga Landscape: implications for conservation and livelihoods.

PubMed

Uprety, Yadav; Poudel, Ram C; Gurung, Janita; Chettri, Nakul; Chaudhary, Ram P

2016-05-03

Non-timber Forest Products (NTFPs), an important provisioning ecosystem services, are recognized for their contribution in rural livelihoods and forest conservation. Effective management through sustainable harvesting and market driven commercialization are two contrasting aspects that are bringing challenges in development of NTFPs sector. Identifying potential species having market value, conducting value chain analyses, and sustainable management of NTFPs need analysis of their use patterns by communities and trends at a regional scale. We analyzed use patterns, trends, and challenges in traditional use and management of NTFPs in the southern slope of Kangchenjunga Landscape, Eastern Himalaya and discussed potential implications for conservation and livelihoods. A total of 739 species of NTFPs used by the local people of Kangchenjunga Landscape were reported in the reviewed literature. Of these, the highest number of NTFPs was documented from India (377 species), followed by Nepal (363) and Bhutan (245). Though the reported species were used for 24 different purposes, medicinal and edible plants were the most frequently used NTFP categories in the landscape. Medicinal plants were used in 27 major ailment categories, with the highest number of species being used for gastro-intestinal disorders. Though the Kangchenjunga Landscape harbors many potential NTFPs, trade of NTFPs was found to be nominal indicating lack of commercialization due to limited market information. We found that the unsustainable harvesting and lack of marketing were the major constraints for sustainable management of NTFPs sector in the landscape despite of promising policy provisions. We suggest sustainable harvesting practices, value addition at local level, and marketing for promotion of NTFPs in the Kangchenjunga Landscape for income generation and livelihood improvement that subsequently contributes to conservation.

Translational Challenges in Cardiovascular Tissue Engineering.

PubMed

Emmert, Maximilian Y; Fioretta, Emanuela S; Hoerstrup, Simon P

2017-04-01

Valvular heart disease and congenital heart defects represent a major cause of death around the globe. Although current therapy strategies have rapidly evolved over the decades and are nowadays safe, effective, and applicable to many affected patients, the currently used artificial prostheses are still suboptimal. They do not promote regeneration, physiological remodeling, or growth (particularly important aspects for children) as their native counterparts. This results in the continuous degeneration and subsequent failure of these prostheses which is often associated with an increased morbidity and mortality as well as the need for multiple re-interventions. To overcome this problem, the concept of tissue engineering (TE) has been repeatedly suggested as a potential technology to enable native-like cardiovascular replacements with regenerative and growth capacities, suitable for young adults and children. However, despite promising data from pre-clinical and first clinical pilot trials, the translation and clinical relevance of such TE technologies is still very limited. The reasons that currently limit broad clinical adoption are multifaceted and comprise of scientific, clinical, logistical, technical, and regulatory challenges which need to be overcome. The aim of this review is to provide an overview about the translational problems and challenges in current TE approaches. It further suggests directions and potential solutions on how these issues may be efficiently addressed in the future to accelerate clinical translation. In addition, a particular focus is put on the current regulatory guidelines and the associated challenges for these promising TE technologies.

Qualitative analysis of round-table discussions on the business case and procurement challenges for hospital electronic prescribing systems.

PubMed

Cresswell, Kathrin M; Slee, Ann; Coleman, Jamie; Williams, Robin; Bates, David W; Sheikh, Aziz

2013-01-01

There is a pressing need to understand the challenges surrounding procurement of and business case development for hospital electronic prescribing systems, and to identify possible strategies to enhance the efficiency of these processes in order to assist strategic decision making. We organized eight multi-disciplinary round-table discussions in the United Kingdom. Participants included policy makers, representatives from hospitals, system developers, academics, and patients. Each discussion was digitally audio-recorded, transcribed verbatim and, together with accompanying field notes, analyzed thematically with NVivo9. We drew on data from 17 participants (approximately eight per roundtable), six hours of discussion, and 15 pages of field notes. Key challenges included silo planning with systems not being considered as part of an integrated organizational information technology strategy, lack of opportunity for interactions between customers and potential suppliers, lack of support for hospitals in choosing appropriate systems, difficulty of balancing structured planning with flexibility, and the on-going challenge of distinguishing "wants" and aspirations from organizational "needs". Development of business cases for major investments in information technology does not take place in an organizational vacuum. Building on previously identified potentially transferable dimensions to the development and execution of business cases surrounding measurements of costs/benefits and risk management, we have identified additional components relevant to ePrescribing systems. These include: considerations surrounding strategic context, case for change and objectives, future service requirements and options appraisal, capital and revenue implications, timescale and deliverability, and risk analysis and management.

Accepting, understanding, teaching, and learning (human) evolution: Obstacles and opportunities.

PubMed

Pobiner, Briana

2016-01-01

Questions about our origin as a species are universal and compelling. Evolution-and in particular human evolution-is a subject that generates intense interest across the world, evidenced by the fact that fossil and DNA discoveries grace the covers of major science journals and magazines as well as other popular print and online media. However, virtually all national polls indicate that the majority of Americans strongly reject biological evolution as a fact-based, well-tested, and robust understanding of the history of life. In the popular mind, no topic in all of science is more contentious or polarizing than evolution and media sources often only serve to magnify this polarization by covering challenges to the teaching of evolution. In the realm of teaching, debates about evolution have shaped textbooks, curricula, standards, and policy. Challenges to accepting and understanding evolution include mistrust and denial of science, cognitive obstacles and misconceptions, language and terminology, and a religious worldview, among others. Teachers, who are on the front lines of these challenges, must be armed with the tools and techniques to teach evolution in formal education settings across grades K-16 in a straightforward, thorough, and sensitive way. Despite the potentially controversial topic of human evolution, growing research is demonstrating that a pedagogical focus on human examples is an effective and engaging way to teach core concepts of evolutionary biology. © 2016 Wiley Periodicals, Inc.

Gelatin controversies in food, pharmaceuticals, and personal care products: Authentication methods, current status, and future challenges.

PubMed

Ali, Eaqub; Sultana, Sharmin; Hamid, Sharifah Bee Abd; Hossain, Motalib; Yehya, Wageeh A; Kader, Abdul; Bhargava, Suresh K

2018-06-13

Gelatin is a highly purified animal protein of pig, cow, and fish origins and is extensively used in food, pharmaceuticals, and personal care products. However, the acceptability of gelatin products greatly depends on the animal sources of the gelatin. Porcine and bovine gelatins have attractive features but limited acceptance because of religious prohibitions and potential zoonotic threats, whereas fish gelatin is welcomed in all religions and cultures. Thus, source authentication is a must for gelatin products but it is greatly challenging due to the breakdown of both protein and DNA biomarkers in processed gelatins. Therefore, several methods have been proposed for gelatin identification, but a comprehensive and systematic document that includes all of the techniques does not exist. This up-to-date review addresses this research gap and presents, in an accessible format, the major gelatin source authentication techniques, which are primarily nucleic acid and protein based. Instead of presenting these methods in paragraph form which needs much attention in reading, the major methods are schematically depicted, and their comparative features are tabulated. Future technologies are forecasted, and challenges are outlined. Overall, this review paper has the merit to serve as a reference guide for the production and application of gelatin in academia and industry and will act as a platform for the development of improved methods for gelatin authentication.

Development of Antibody Therapeutics against Flaviviruses

PubMed Central

Sun, Haiyan; Chen, Qiang; Lai, Huafang

2017-01-01

Recent outbreaks of Zika virus (ZIKV) highlight the urgent need to develop efficacious interventions against flaviviruses, many of which cause devastating epidemics around the world. Monoclonal antibodies (mAb) have been at the forefront of treatment for cancer and a wide array of other diseases due to their specificity and potency. While mammalian cell-produced mAbs have shown promise as therapeutic candidates against several flaviviruses, their eventual approval for human application still faces several challenges including their potential risk of predisposing treated patients to more severe secondary infection by a heterologous flavivirus through antibody-dependent enhancement (ADE). The high cost associated with mAb production in mammalian cell cultures also poses a challenge for the feasible application of these drugs to the developing world where the majority of flavivirus infection occurs. Here, we review the current therapeutic mAb candidates against various flaviviruses including West Nile (WNV), Dengue virus (DENV), and ZIKV. The progress of using plants for developing safer and more economical mAb therapeutics against flaviviruses is discussed within the context of their expression, characterization, downstream processing, neutralization, and in vivo efficacy. The progress of using plant glycoengineering to address ADE, the major impediment of flavivirus therapeutic development, is highlighted. These advancements suggest that plant-based systems are excellent alternatives for addressing the remaining challenges of mAb therapeutic development against flavivirus and may facilitate the eventual commercialization of these drug candidates. PMID:29295568

Charting the landscape of priority problems in psychiatry, part 1: classification and diagnosis.

PubMed

Stephan, Klaas E; Bach, Dominik R; Fletcher, Paul C; Flint, Jonathan; Frank, Michael J; Friston, Karl J; Heinz, Andreas; Huys, Quentin J M; Owen, Michael J; Binder, Elisabeth B; Dayan, Peter; Johnstone, Eve C; Meyer-Lindenberg, Andreas; Montague, P Read; Schnyder, Ulrich; Wang, Xiao-Jing; Breakspear, Michael

2016-01-01

Contemporary psychiatry faces major challenges. Its syndrome-based disease classification is not based on mechanisms and does not guide treatment, which largely depends on trial and error. The development of therapies is hindered by ignorance of potential beneficiary patient subgroups. Neuroscientific and genetics research have yet to affect disease definitions or contribute to clinical decision making. In this challenging setting, what should psychiatric research focus on? In two companion papers, we present a list of problems nominated by clinicians and researchers from different disciplines as candidates for future scientific investigation of mental disorders. These problems are loosely grouped into challenges concerning nosology and diagnosis (this Personal View) and problems related to pathogenesis and aetiology (in the companion Personal View). Motivated by successful examples in other disciplines, particularly the list of Hilbert's problems in mathematics, this subjective and eclectic list of priority problems is intended for psychiatric researchers, helping to re-focus existing research and providing perspectives for future psychiatric science. Copyright © 2016 Elsevier Ltd. All rights reserved.

Non-Invasive Breast Cancer Diagnosis through Electrochemical Biosensing at Different Molecular Levels

PubMed Central

Campuzano, Susana

2017-01-01

The rapid and accurate determination of specific circulating biomarkers at different molecular levels with non- or minimally invasive methods constitutes a major challenge to improve the breast cancer outcomes and life quality of patients. In this field, electrochemical biosensors have demonstrated to be promising alternatives against more complex conventional strategies to perform fast, accurate and on-site determination of circulating biomarkers at low concentrations in minimally treated body fluids. In this article, after discussing briefly the relevance and current challenges associated with the determination of breast cancer circulating biomarkers, an updated overview of the electrochemical affinity biosensing strategies emerged in the last 5 years for this purpose is provided highlighting the great potentiality of these methodologies. After critically discussing the most interesting features of the electrochemical strategies reported so far for the single or multiplexed determination of such biomarkers with demonstrated applicability in liquid biopsy analysis, existing challenges still to be addressed and future directions in this field will be pointed out. PMID:28858236

Building Evidence for Health: Green Buildings, Current Science, and Future Challenges.

PubMed

Cedeño-Laurent, J G; Williams, A; MacNaughton, P; Cao, X; Eitland, E; Spengler, J; Allen, J

2018-04-01

Civilizational challenges have questioned the status quo of energy and material consumption by humans. From the built environment perspective, a response to these challenges was the creation of green buildings. Although the revolutionary capacity of the green building movement has elevated the expectations of new commercial construction, its rate of implementation has secluded the majority of the population from its benefits. Beyond reductions in energy usage and increases in market value, the main strength of green buildings may be the procurement of healthier building environments. Further pursuing the right to healthy indoor environments could help the green building movement to attain its full potential as a transformational public health tool. On the basis of 40 years of research on indoor environmental quality, we present a summary of nine environment elements that are foundational to human health. We posit the role of green buildings as a critical research platform within a novel sustainability framework based on social-environmental capital assets.

Design and Analysis of Offshore Macroalgae Biorefineries.

PubMed

Golberg, Alexander; Liberzon, Alexander; Vitkin, Edward; Yakhini, Zohar

2018-03-15

Displacing fossil fuels and their derivatives with renewables, and increasing sustainable food production are among the major challenges facing the world in the coming decades. A possible, sustainable direction for addressing this challenge is the production of biomass and the conversion of this biomass to the required products through a complex system coined biorefinery. Terrestrial biomass and microalgae are possible sources; however, concerns over net energy balance, potable water use, environmental hazards, and uncertainty in the processing technologies raise questions regarding their actual potential to meet the anticipated food, feed, and energy challenges in a sustainable way. Alternative sustainable sources for biorefineries are macroalgae grown and processed offshore. However, implementation of the offshore biorefineries requires detailed analysis of their technological, economic, and environmental performance. In this chapter, the basic principles of marine biorefineries design are shown. The methods to integrate thermodynamic efficiency, investment, and environmental aspects are discussed. The performance improvement by development of new cultivation methods that fit macroalgae physiology and development of new fermentation methods that address macroalgae unique chemical composition is shown.

Capability challenges of facility management (FM) personnel toward sustainability agenda

NASA Astrophysics Data System (ADS)

Halim, Ahmad Ilyas Ahmad; Sarpin, Norliana; Kasim, Narimah Binti; Zainal, Rozlin Binti

2017-10-01

The industries business play a significant role to contribute toward economic growth in develop and developing country. However, they always face serious problems such as time overrun, waste generation, and cost overrun during their operation and maintenance. Traditional practice is found unable to control that situation. These challenges accent the need for practitioners to rethink and improve their process management. This show that industries business has major potential when applying sustainable development by focusing on three pillars (economic, environment, and social). By adopting sustainability, it can reduce energy consumption and waste, while increasing productivity, financial return and corporate standing in community. FM personnel are most suitable position to lead organizations toward sustainability implementation. However, lack of skill and capability among FM personnel to achieve sustainable goal had become barrier that need to overcome. This paper focus to identify capability challenges of FM personnel toward sustainability. A multiple researches were conducted and data were gathered through literature review from previous studies.

Correlates of protection for rotavirus vaccines: Possible alternative trial endpoints, opportunities, and challenges.

PubMed

Angel, Juana; Steele, A Duncan; Franco, Manuel A

2014-01-01

Rotavirus (RV) is a major vaccine-preventable killer of young children worldwide. Two RV vaccines are globally commercially available and other vaccines are in different stages of development. Due to the absence of a suitable correlate of protection (CoP), all RV vaccine efficacy trials have had clinical endpoints. These trials represent an important challenge since RV vaccines have to be introduced in many different settings, placebo-controlled studies are unethical due to the availability of licensed vaccines, and comparator assessments for new vaccines with clinical endpoints are very large, complex, and expensive to conduct. A CoP as a surrogate endpoint would allow predictions of vaccine efficacy for new RV vaccines and enable a regulatory pathway, contributing to the more rapid development of new RV vaccines. The goal of this review is to summarize experiences from RV natural infection and vaccine studies to evaluate potential CoP for use as surrogate endpoints for assessment of new RV vaccines, and to explore challenges and opportunities in the field.

Evaluation of lipopolysaccharide and capsular polysaccharide as subunit vaccines against experimental melioidosis.

PubMed

Nelson, Michelle; Prior, Joann L; Lever, M Stephen; Jones, Helen E; Atkins, Timothy P; Titball, Richard W

2004-12-01

Burkholderia pseudomallei is the causative agent of melioidosis, which is a major cause of morbidity and mortality in endemic regions. Currently there is no human vaccine against melioidosis. In this study, LPS or capsular polysaccharide was used to immunize BALB/c mice. The different polysaccharide antigens induced antibody responses. Mice vaccinated with LPS developed predominantly IgM and IgG3 responses. Contrastingly, mice vaccinated with capsular polysaccharide developed a predominantly IgG2b response. After immunization, mice were challenged by the intra-peritoneal route and an increased mean time to death was observed compared with unvaccinated controls. Immunization with LPS provided an optimal protective response. Mice challenged by the aerosol route showed a small increase in the mean time to death compared with the unvaccinated controls. The passive transfer of antigen from immunized into naive mice provided protection against a subsequent challenge. This study is the first time antigens protective by active immunization have been identified and suggests that polysaccharides have potential as vaccine candidates against melioidosis.

Reduction or discontinuation of antipsychotics for challenging behaviour in adults with intellectual disability: a systematic review.

PubMed

Sheehan, Rory; Hassiotis, Angela

2017-03-01

The use of antipsychotics to manage challenging behaviour in adults with intellectual disability is widespread but controversial, and evidence is scarce. There is a perception that antipsychotics used in this context can be reduced or discontinued, and this has been a major focus of recent national policy. However, such an intervention risks harm as well as having potential benefits. We reviewed the available evidence and found that antipsychotics can be reduced or discontinued in a substantial proportion of adults who use them for challenging behaviour, although not always without adverse effects. There is a group which displays behavioural deterioration on antipsychotic reduction that prevents discontinuation; predictors of poor response could not be reliably identified. In view of the relatively scarce data and methodological limitations of the available studies, we cannot draw firm conclusions to inform a population level approach to this issue. Antipsychotic medication used for behaviour should be reviewed regularly and an individualised approach taken to treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficient generation of hPSC-derived midbrain dopaminergic neurons in a fully defined, scalable, 3D biomaterial platform

PubMed Central

Adil, Maroof M.; Rodrigues, Gonçalo M. C.; Kulkarni, Rishikesh U.; Rao, Antara T.; Chernavsky, Nicole E.; Miller, Evan W.; Schaffer, David V.

2017-01-01

Pluripotent stem cells (PSCs) have major potential as an unlimited source of functional cells for many biomedical applications; however, the development of cell manufacturing systems to enable this promise faces many challenges. For example, there have been major recent advances in the generation of midbrain dopaminergic (mDA) neurons from stem cells for Parkinson’s Disease (PD) therapy; however, production of these cells typically involves undefined components and difficult to scale 2D culture formats. Here, we used a fully defined, 3D, thermoresponsive biomaterial platform to rapidly generate large numbers of action-potential firing mDA neurons after 25 days of differentiation (~40% tyrosine hydroxylase (TH) positive, maturing into 25% cells exhibiting mDA neuron-like spiking behavior). Importantly, mDA neurons generated in 3D exhibited a 30-fold increase in viability upon implantation into rat striatum compared to neurons generated on 2D, consistent with the elevated expression of survival markers FOXA2 and EN1 in 3D. A defined, scalable, and resource-efficient cell culture platform can thus rapidly generate high quality differentiated cells, both neurons and potentially other cell types, with strong potential to accelerate both basic and translational research. PMID:28091566

Towards Increased Engagement of Geoscientists in Global Development Frameworks

NASA Astrophysics Data System (ADS)

Gill, Joel

2016-04-01

Geoscientists have the potential to make a significant contribution to tackling some of the major socio-environmental challenges of today, including extreme poverty, sustainable development, disaster risk reduction and climate change. This presentation explores the importance and social responsibility of geoscientists to engage in such work through understanding and supporting key global development frameworks. During 2015 the international community agreed three important agendas for change. Each framework relates to the intersection of environmental processes with human activities and behaviours, addressing significant challenges affecting society. The frameworks are (i) the UN Global Goals for Sustainable Development, (ii) the Sendai Framework for Disaster Risk Reduction 2015-2030, and (iii) subject to final confirmation at the time of writing, an agreement on climate change at the Paris Conference of the Parties - COP21. The UN Global Goals for Sustainable Development, for example, includes 17 goals aiming to end extreme poverty, fight inequality and ensure environmental sustainability. Specific goals relate to clean water and sanitation, clean and affordable energy, the development of resilient infrastructure, and the need for climate action. Given this context, here (i) a synthesis is presented of the role of geoscience in successfully achieving these major global development frameworks agreed in 2015, (ii) the ethical and social understanding that underpins effective engagement by geoscientists in the science-policy-practice interface is discussed, and (iii) this required ethical understanding is placed into the context of geoscience training and development needs. This approach demonstrates the importance of geoscientists from across all sectors and specialisms, engaging in the implementation, monitoring and evaluation of global development frameworks. It highlights the importance of a greater awareness and consideration of our ethical responsibilities in order to better support efforts to tackle major societal challenges.

Evaluating the physiological reserves of older patients with cancer: the value of potential biomarkers of aging?

PubMed

Pallis, Athanasios G; Hatse, Sigrid; Brouwers, Barbara; Pawelec, Graham; Falandry, Claire; Wedding, Ulrich; Lago, Lissandra Dal; Repetto, Lazzaro; Ring, Alistair; Wildiers, Hans

2014-04-01

Aging of an individual entails a progressive decline of functional reserves and loss of homeostasis that eventually lead to mortality. This process is highly individualized and is influenced by multiple genetic, epigenetic and environmental factors. This individualization and the diversity of factors influencing aging result in a significant heterogeneity among people with the same chronological age, representing a major challenge in daily oncology practice. Thus, many factors other than mere chronological age will contribute to treatment tolerance and outcome in the older patients with cancer. Clinical/comprehensive geriatric assessment can provide information on the general health status of individuals, but is far from perfect as a prognostic/predictive tool for individual patients. On the other hand, aging can also be assessed in terms of biological changes in certain tissues like the blood compartment which result from adaptive alterations due to past history of exposures, as well as intrinsic aging processes. There are major signs of 'aging' in lymphocytes (e.g. lymphocyte subset distribution, telomere length, p16INK4A expression), and also in (inflammatory) cytokine expression and gene expression patterns. These result from a combination of the above two processes, overlaying genetic predispositions which contribute significantly to the aging phenotype. These potential "aging biomarkers" might provide additional prognostic/predictive information supplementing clinical evaluation. The purpose of the current paper is to describe the most relevant potential "aging biomarkers" (markers that indicate the biological functional age of patients) which focus on the biological background, the (limited) available clinical data, and technical challenges. Despite their great potential interest, there is a need for much more (validated) clinical data before these biomarkers could be used in a routine clinical setting. This manuscript tries to provide a guideline on how these markers can be integrated in future research aimed at providing such data. © 2013.

Exploring consumer pathways and patterns of use for ...

EPA Pesticide Factsheets

Background: Humans may be exposed to thousands of chemicals through contact in the workplace, home, and via air, water, food, and soil. A major challenge is estimating exposures to these chemicals, which requires understanding potential exposure routes directly related to how chemicals are used. Objectives: We aimed to assign “use categories” to a database of chemicals, including ingredients in consumer products, to help prioritize which chemicals will be given more scrutiny relative to human exposure potential and target populations. The goal was to identify (a) human activities that result in increased chemical exposure while (b) simplifying the dimensionality of hazard assessment for risk characterization. Methods: Major data sources on consumer- and industrial-process based chemical uses were compiled from multiple countries, including from regulatory agencies, manufacturers, and retailers. The resulting categorical chemical use and functional information are presented through the Chemical/Product Categories Database (CPCat). Results: CPCat contains information on 43,596 unique chemicals mapped to 833 terms categorizing their usage or function. Examples presented demonstrate potential applications of the CPCat database, including the identification of chemicals to which children may be exposed (including those that are not identified on product ingredient labels), and prioritization of chemicals for toxicity screening. The CPCat database is availabl

A novel role for bioactive lipids in stem cell mobilization during cardiac ischemia

PubMed Central

Nagareddy, Prabhakara R.; Asfour, Ahmed; Klyachkin, Yuri M.; Abdel-Latif, Ahmed

2014-01-01

Despite major advances in pharmacological and reperfusion therapies, regenerating and/or replacing the infarcted myocardial tissue is an enormous challenge and therefore ischemic heart disease (IHD) remains a major cause of mortality and morbidity worldwide. Adult bone marrow is home for a variety of hematopoietic and non-hematopoietic stem cells including a small subset of primitive cells that carry a promising regenerative potential. It is now well established that myocardial ischemia (MI) induces mobilization of bone marrow-derived cells including differentiated lineage as well as undifferentiated stem cells. While the numbers of stem cells carrying pluripotent features among the mobilized stem cells is small, their regenerative capacity appears immense. Therapies aimed at selective mobilization of these pluripotent stem cells during myocardial ischemia have a promising potential to regenerate the injured myocardium. Emerging evidence suggest that bioactive sphingolipids such as sphingosine-1 phosphate and ceramide-1 phosphate hold a great promise in selective mobilization of pluripotent stem cells to the infarcted region during MI. This review highlights the recent advances in the mechanisms of stem cell mobilization and provides newer evidence in support of bioactive lipids as potential therapeutic agents in the treatment of ischemic heart disease. PMID:24318213

Evaluation of the Department of the Navy’s (DoN’s) Managers Internal Control (MIC) Manual

DTIC Science & Technology

2008-12-01

50 e. Managing Risk during Change (Major Factor #5) ...............50 3. Control Activities...Five Standards of Internal Management Controls as Control Environment, Risk Assessment, Control Activities, Information and Communication, and...Major Management Challenges In 2003, GAO produced another report titled Major Management Challenges and Program Risks for the DoD. This report

Synthetic transitions: towards a new synthesis

PubMed Central

Solé, Ricard

2016-01-01

The evolution of life in our biosphere has been marked by several major innovations. Such major complexity shifts include the origin of cells, genetic codes or multicellularity to the emergence of non-genetic information, language or even consciousness. Understanding the nature and conditions for their rise and success is a major challenge for evolutionary biology. Along with data analysis, phylogenetic studies and dedicated experimental work, theoretical and computational studies are an essential part of this exploration. With the rise of synthetic biology, evolutionary robotics, artificial life and advanced simulations, novel perspectives to these problems have led to a rather interesting scenario, where not only the major transitions can be studied or even reproduced, but even new ones might be potentially identified. In both cases, transitions can be understood in terms of phase transitions, as defined in physics. Such mapping (if correct) would help in defining a general framework to establish a theory of major transitions, both natural and artificial. Here, we review some advances made at the crossroads between statistical physics, artificial life, synthetic biology and evolutionary robotics. This article is part of the themed issue ‘The major synthetic evolutionary transitions’. PMID:27431516

Chapter 10: Research and Deployment of Renewable Bioenergy Production from Microalgae

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

Laurens, Lieve M; Glasser, Melodie

Recent progress towards the implementation of renewable bioenergy production has included microalgae, which have potential to significantly contribute to a viable future bioeconomy. In a current challenging energy landscape, where an increased demand for renewable fuels is projected and accompanied by plummeting fossil fuels' prices, economical production of algae-based fuels becomes more challenging. However, in the context of mitigating carbon emissions with the potential of algae to assimilate large quantities of CO2, there is a route to drive carbon sequestration and utilization to support a sustainable and secure global energy future. This chapter places international energy policy in the contextmore » of the current and projected energy landscape. The contribution that algae can make, is summarized as both a conceptual contribution as well as an overview of the commercial infrastructure installed globally. Some of the major recent developments and crucial technology innovations are the results of global government support for the development of algae-based bioenergy, biofuels and bioproduct applications, which have been awarded as public private partnerships and are summarized in this chapter.« less

Genome Editing Tools in Plants

PubMed Central

Mohanta, Tapan Kumar; Bashir, Tufail; Hashem, Abeer; Bae, Hanhong

2017-01-01

Genome editing tools have the potential to change the genomic architecture of a genome at precise locations, with desired accuracy. These tools have been efficiently used for trait discovery and for the generation of plants with high crop yields and resistance to biotic and abiotic stresses. Due to complex genomic architecture, it is challenging to edit all of the genes/genomes using a particular genome editing tool. Therefore, to overcome this challenging task, several genome editing tools have been developed to facilitate efficient genome editing. Some of the major genome editing tools used to edit plant genomes are: Homologous recombination (HR), zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), pentatricopeptide repeat proteins (PPRs), the CRISPR/Cas9 system, RNA interference (RNAi), cisgenesis, and intragenesis. In addition, site-directed sequence editing and oligonucleotide-directed mutagenesis have the potential to edit the genome at the single-nucleotide level. Recently, adenine base editors (ABEs) have been developed to mutate A-T base pairs to G-C base pairs. ABEs use deoxyadeninedeaminase (TadA) with catalytically impaired Cas9 nickase to mutate A-T base pairs to G-C base pairs. PMID:29257124

Shark recreational fisheries: Status, challenges, and research needs.

PubMed

Gallagher, Austin J; Hammerschlag, Neil; Danylchuk, Andy J; Cooke, Steven J

2017-05-01

For centuries, the primary manner in which humans have interacted with sharks has been fishing. A combination of their slow-growing nature and high use-values have resulted in population declines for many species around the world, and to date the vast majority of fisheries-related work on sharks has focused on the commercial sector. Shark recreational fishing remains an overlooked area of research despite the fact that these practices are popular globally and could present challenges to their populations. Here we provide a topical overview of shark recreational fisheries, highlighting their history and current status. While recreational fishing can provide conservation benefits under certain circumstances, we focus our discourse on the relatively understudied, potentially detrimental impacts these activities may have on shark physiology, behavior, and fitness. We took this angle given the realized but potentially underestimated significance of recreational fishing for shark conservation management plans and stock assessments, in hopes of creating a dialogue around sustainability. We also present a series of broad and focused research questions and underpin areas of future research need to assist with the development of this emergent area of research.

The Potential of Automatic Word Comparison for Historical Linguistics.

PubMed

List, Johann-Mattis; Greenhill, Simon J; Gray, Russell D

2017-01-01

The amount of data from languages spoken all over the world is rapidly increasing. Traditional manual methods in historical linguistics need to face the challenges brought by this influx of data. Automatic approaches to word comparison could provide invaluable help to pre-analyze data which can be later enhanced by experts. In this way, computational approaches can take care of the repetitive and schematic tasks leaving experts to concentrate on answering interesting questions. Here we test the potential of automatic methods to detect etymologically related words (cognates) in cross-linguistic data. Using a newly compiled database of expert cognate judgments across five different language families, we compare how well different automatic approaches distinguish related from unrelated words. Our results show that automatic methods can identify cognates with a very high degree of accuracy, reaching 89% for the best-performing method Infomap. We identify the specific strengths and weaknesses of these different methods and point to major challenges for future approaches. Current automatic approaches for cognate detection-although not perfect-could become an important component of future research in historical linguistics.

The Potential of Automatic Word Comparison for Historical Linguistics

PubMed Central

Greenhill, Simon J.; Gray, Russell D.

2017-01-01

The amount of data from languages spoken all over the world is rapidly increasing. Traditional manual methods in historical linguistics need to face the challenges brought by this influx of data. Automatic approaches to word comparison could provide invaluable help to pre-analyze data which can be later enhanced by experts. In this way, computational approaches can take care of the repetitive and schematic tasks leaving experts to concentrate on answering interesting questions. Here we test the potential of automatic methods to detect etymologically related words (cognates) in cross-linguistic data. Using a newly compiled database of expert cognate judgments across five different language families, we compare how well different automatic approaches distinguish related from unrelated words. Our results show that automatic methods can identify cognates with a very high degree of accuracy, reaching 89% for the best-performing method Infomap. We identify the specific strengths and weaknesses of these different methods and point to major challenges for future approaches. Current automatic approaches for cognate detection—although not perfect—could become an important component of future research in historical linguistics. PMID:28129337

Electrochemistry-based Approaches to Low Cost, High Sensitivity, Automated, Multiplexed Protein Immunoassays for Cancer Diagnostics

PubMed Central

Dixit, Chandra K.; Kadimisetty, Karteek; Otieno, Brunah A.; Tang, Chi; Malla, Spundana; Krause, Colleen E.; Rusling, James F.

2015-01-01

Early detection and reliable diagnostics are keys to effectively design cancer therapies with better prognoses. Simultaneous detection of panels of biomarker proteins holds great promise as a general tool for reliable cancer diagnostics. A major challenge in designing such a panel is to decide upon a coherent group of biomarkers which have higher specificity for a given type of cancer. The second big challenge is to develop test devices to measure these biomarkers quantitatively with high sensitivity and specificity, such that there are no interferences from the complex serum or tissue matrices. Lastly, integrating all these tests into a technology that doesn’t require exclusive training to operate, and can be used at point-of-care (POC) is another potential bottleneck in futuristic cancer diagnostics. In this article, we review electrochemistry-based tools and technologies developed and/or used in our laboratories to construct low-cost microfluidic protein arrays for highly sensitive detection of the panel of cancer-specific biomarkers with high specificity and at the same time have the potential to be translated into a POC. PMID:26525998

Electrochemistry-based approaches to low cost, high sensitivity, automated, multiplexed protein immunoassays for cancer diagnostics.

PubMed

Dixit, Chandra K; Kadimisetty, Karteek; Otieno, Brunah A; Tang, Chi; Malla, Spundana; Krause, Colleen E; Rusling, James F

2016-01-21

Early detection and reliable diagnostics are keys to effectively design cancer therapies with better prognoses. The simultaneous detection of panels of biomarker proteins holds great promise as a general tool for reliable cancer diagnostics. A major challenge in designing such a panel is to decide upon a coherent group of biomarkers which have higher specificity for a given type of cancer. The second big challenge is to develop test devices to measure these biomarkers quantitatively with high sensitivity and specificity, such that there are no interferences from the complex serum or tissue matrices. Lastly, integrating all these tests into a technology that does not require exclusive training to operate, and can be used at point-of-care (POC) is another potential bottleneck in futuristic cancer diagnostics. In this article, we review electrochemistry-based tools and technologies developed and/or used in our laboratories to construct low-cost microfluidic protein arrays for the highly sensitive detection of a panel of cancer-specific biomarkers with high specificity which at the same time has the potential to be translated into POC applications.

Signaling pathway cloud regulation for in silico screening and ranking of the potential geroprotective drugs

PubMed Central

Zhavoronkov, Alex; Buzdin, Anton A.; Garazha, Andrey V.; Borisov, Nikolay M.; Moskalev, Alexey A.

2014-01-01

The major challenges of aging research include absence of the comprehensive set of aging biomarkers, the time it takes to evaluate the effects of various interventions on longevity in humans and the difficulty extrapolating the results from model organisms to humans. To address these challenges we propose the in silico method for screening and ranking the possible geroprotectors followed by the high-throughput in vivo and in vitro validation. The proposed method evaluates the changes in the collection of activated or suppressed signaling pathways involved in aging and longevity, termed signaling pathway cloud, constructed using the gene expression data and epigenetic profiles of young and old patients' tissues. The possible interventions are selected and rated according to their ability to regulate age-related changes and minimize differences in the signaling pathway cloud. While many algorithmic solutions to simulating the induction of the old into young metabolic profiles in silico are possible, this flexible and scalable approach may potentially be used to predict the efficacy of the many drugs that may extend human longevity before conducting pre-clinical work and expensive clinical trials. PMID:24624136

An exploration of opportunities and challenges facing cervical cancer managers in Kenya

PubMed Central

2013-01-01

Background Kenya like other developing countries is low in resource setting and is facing a number of challenges in the management of cervical cancer. This study documents opportunities and challenges encountered in managing cervical cancer from the health care workers’ perspectives. A qualitative study was conducted among cervical cancer managers who were defined as nurses and doctors involved in operational level management of cervical cancer. The respondents were drawn from four provincial hospitals and the only two main National public referral hospitals in Kenya. Twenty one [21] nurse managers and twelve [12] medical doctors were interviewed using a standardized interview guide. The responses were audio recorded, transcribed verbatim and the content analyzed in emerging themes. Findings Four themes were identified. Patient related challenges included a large number of patients, presenting in the late stage of disease, low levels of knowledge on cancer of the cervix, low levels of screening and a poor attitude towards screening procedure. Individual health care providers identified a lack of specialised training, difficulty in disclosure of diagnosis to patients, a poor attitude towards cervical cancer screening procedure and a poor attitude towards cervical cancer patients. Health facilities were lacking in infrastructure and medical supplies. Some managers felt ill-equipped in technological skills while the majority lacked access to the internet. Mobile phones were identified as having great potential for improving the management of cervical cancer in Kenya. Conclusion Kenya faces a myriad of challenges in the management of cervical cancer. The peculiar negative attitude towards screening procedure and the negative attitude of some managers towards cervical cancer patients need urgent attention. The potential use of mobile phones in cervical cancer management should be explored. PMID:23566436

Adverse events and the relation with quality of life in adults with intellectual disability and challenging behaviour using psychotropic drugs.

PubMed

Scheifes, Arlette; Walraven, Sanne; Stolker, Joost Jan; Nijman, Henk L I; Egberts, Toine C G; Heerdink, Eibert R

2016-01-01

Psychotropic drugs are prescribed to approximately 30-40% of adults with intellectual disability (ID) and challenging behaviour, despite the limited evidence of effectiveness and the potential of adverse events. To assess the prevalence of adverse events in association with psychotropic drug use in adults with ID and challenging behaviour and to examine the relation of these adverse events with the person's quality of life. The presence of adverse events was measured with a questionnaire that had to be filled in by the physicians of the participants. Movement disorders were measured separately with a standardised protocol. The strength of the association between adverse events and Intellectual Disability Quality of Life-16 (IDQOL-16), and daily functioning was investigated using linear regression analyses, taking into account the severity of disease (CGI-S) as potential confounder. Virtually all of 103 adults with ID and challenging behaviour had at least one adverse event (84.4%) and almost half had ≥3 adverse events (45.6%) across different subclasses. Using psychotropic drugs increased the prevalence of adverse events significantly. Respectively 13% of the patients without psychotropic drugs and 61% of the patients with ≥2 psychotropic drugs had ≥3 adverse events. Having adverse events had a significantly negative influence on the quality of life. A large majority of all patients had at least one adverse event associated with psychotropic drug use. More attention is needed for these adverse events and their negative influence on the quality of life of these patients, taking into account the lack of evidence of effectiveness of psychotropic drugs for challenging behaviour. Copyright © 2015. Published by Elsevier Ltd.

Long-Term Pain and Recovery After Major Pediatric Surgery: A Qualitative Study With Teens, Parents, and Perioperative Care Providers.

PubMed

Rabbitts, Jennifer A; Aaron, Rachel V; Fisher, Emma; Lang, Emily A; Bridgwater, Caroline; Tai, Gabrielle Ghafari; Palermo, Tonya M

2017-07-01

Research developing targeted treatment focused on coping with children's long-term pain after surgery is needed because of the high prevalence of chronic pain after surgery. This qualitative study aimed to: 1) understand the child's and family's experiences of pain over the course of their surgical experience, and 2) gather stakeholder input regarding potential barriers and facilitators of perioperative intervention delivery. Fifteen children ages 10 to 18 years who underwent recent major surgery, their primary caregivers, and 17 perioperative health care providers were interviewed. Interviews were coded using semantic thematic analysis. The perioperative period presented emotional challenges for families. Families felt unprepared for surgery and pain. Recovery and regaining physical functioning at home was challenging. Families struggled to return to valued activities. Families reported interest in a perioperative psychosocial intervention. Providers endorsed that families would benefit from enhanced coping skills. They emphasized that families would benefit from more detailed preparatory information. Providers suggested that flexible intervention delivery at home would be ideal. Research developing interventions addressing pain and anxiety in children undergoing major surgery is critically needed. The findings of the present study can inform intervention development with the aim of improving short- as well as long-term recovery in children undergoing major surgery. This qualitative study examined children and their parents' experience of long-term pain and recovery after major surgery, identifying barriers and facilitators of perioperative intervention delivery. Families experienced surgery as stressful, and felt underprepared for pain and recovery. Families and health care providers expressed interest in a preoperative intervention teaching coping skills. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Simulation study on compressive laminar optical tomography for cardiac action potential propagation

PubMed Central

Harada, Takumi; Tomii, Naoki; Manago, Shota; Kobayashi, Etsuko; Sakuma, Ichiro

2017-01-01

To measure the activity of tissue at the microscopic level, laminar optical tomography (LOT), which is a microscopic form of diffuse optical tomography, has been developed. However, obtaining sufficient recording speed to determine rapidly changing dynamic activity remains major challenges. For a high frame rate of the reconstructed data, we here propose a new LOT method using compressed sensing theory, called compressive laminar optical tomography (CLOT), in which novel digital micromirror device-based illumination and data reduction in a single reconstruction are applied. In the simulation experiments, the reconstructed volumetric images of the action potentials that were acquired from 5 measured images with random pattern featured a wave border at least to a depth of 2.5 mm. Consequently, it was shown that CLOT has potential for over 200 fps required for the cardiac electrophysiological phenomena. PMID:28736675

Illegal or legitimate use? Precursor compounds to amphetamine and methamphetamine.

PubMed

Musshoff, F

2000-02-01

The interpretation of methamphetamine and amphetamine positive test results in biological samples is a challenge to clinical and forensic toxicology for several reasons. The effects of pH and dilution of urine samples and the knowledge about legitimate and illicit sources have to be taken into account. Besides a potentially legal prescription of amphetamines, many substances metabolize to methamphetamine or amphetamine in the body: amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Especially the knowledge of potential origins of methamphetamine and amphetamine turns out to be very important to prevent a misinterpretation of the surrounding circumstances and to prove illegal drug abuse. In this review, potential precursor compounds are described, including their medical use and major clinical effects and their metabolic profiles, as well as some clues which help to identify the sources.

Bringing Web 2.0 to bioinformatics.

PubMed

Zhang, Zhang; Cheung, Kei-Hoi; Townsend, Jeffrey P

2009-01-01

Enabling deft data integration from numerous, voluminous and heterogeneous data sources is a major bioinformatic challenge. Several approaches have been proposed to address this challenge, including data warehousing and federated databasing. Yet despite the rise of these approaches, integration of data from multiple sources remains problematic and toilsome. These two approaches follow a user-to-computer communication model for data exchange, and do not facilitate a broader concept of data sharing or collaboration among users. In this report, we discuss the potential of Web 2.0 technologies to transcend this model and enhance bioinformatics research. We propose a Web 2.0-based Scientific Social Community (SSC) model for the implementation of these technologies. By establishing a social, collective and collaborative platform for data creation, sharing and integration, we promote a web services-based pipeline featuring web services for computer-to-computer data exchange as users add value. This pipeline aims to simplify data integration and creation, to realize automatic analysis, and to facilitate reuse and sharing of data. SSC can foster collaboration and harness collective intelligence to create and discover new knowledge. In addition to its research potential, we also describe its potential role as an e-learning platform in education. We discuss lessons from information technology, predict the next generation of Web (Web 3.0), and describe its potential impact on the future of bioinformatics studies.

Ecological intensification of cereal production systems: yield potential, soil quality, and precision agriculture.

PubMed

Cassman, K G

1999-05-25

Wheat (Triticum aestivum L.), rice (Oryza sativa L.), and maize (Zea mays L.) provide about two-thirds of all energy in human diets, and four major cropping systems in which these cereals are grown represent the foundation of human food supply. Yield per unit time and land has increased markedly during the past 30 years in these systems, a result of intensified crop management involving improved germplasm, greater inputs of fertilizer, production of two or more crops per year on the same piece of land, and irrigation. Meeting future food demand while minimizing expansion of cultivated area primarily will depend on continued intensification of these same four systems. The manner in which further intensification is achieved, however, will differ markedly from the past because the exploitable gap between average farm yields and genetic yield potential is closing. At present, the rate of increase in yield potential is much less than the expected increase in demand. Hence, average farm yields must reach 70-80% of the yield potential ceiling within 30 years in each of these major cereal systems. Achieving consistent production at these high levels without causing environmental damage requires improvements in soil quality and precise management of all production factors in time and space. The scope of the scientific challenge related to these objectives is discussed. It is concluded that major scientific breakthroughs must occur in basic plant physiology, ecophysiology, agroecology, and soil science to achieve the ecological intensification that is needed to meet the expected increase in food demand.

Positive lithiation potential on functionalized Graphene sheets

NASA Astrophysics Data System (ADS)

Chouhan, Rajiv Kumar; Raghani, Pushpa

2015-03-01

Designing lithium batteries with high capacities is major challenge in the field of energy storage. As an alternative to the conventional graphitic anode with a capacity of ~372 mAhg-1 , we look at the adsorption of lithium on 2D graphene oxide (GO) sheets. We have included van-der-waal's interaction in our calculation and compared with literature showing its importance in Li binding on Graphene sheets. In comparison to the negative lithiation potential in prestine graphene sheets, we were able to get positive lithiation potential by introducing functional groups such as epoxy(-O-) and hydroxyl(-OH) on graphene. Also the non-stoichiometic nature of GO provides better potential to increase the lithiation potential in compare to the defects induced graphene 2D sheet. Dramatic charge redistribution within the sheet due to presence of highly electronegative oxygen plays an important role in increasing the capacity. Financial support from Research Corporation's Cottrell College Science award and National Science Foundation's CAREER award (DMR-1255584). Computational facilities provided by HPC center of Idaho National Laboratory.

Tailoring Modified Moore Method Techniques to Liberal Arts Mathematics Courses

ERIC Educational Resources Information Center

Hitchman, Theron J.; Shaw, Douglas

2015-01-01

Inquiry-based learning (IBL) techniques can be used in mathematics courses for non-majors, such as courses required for liberal arts majors to fulfill graduation requirements. Unique challenges are discussed, followed by adaptations of IBL techniques to overcome those challenges.

Spiritual and natural etiologies on a Polynesian outlier in Papua New Guinea.

PubMed

Feinberg, R

1990-01-01

Several writers have challenged recently the long-held contention that non-Western peoples tend to emphasize spirits, sorcerers, and other supernatural forces in their explanations for the cause of illness. Here, I examine indigenous theories of illness-causation on Nukumanu, a Polynesian outlier atoll in Papua New Guinea. Although Nukumanu invoke mundane as well as supernatural explanations, their major preoccupation is with spirits as etiological agents. In this light, I suggest a number of potential reasons for the difference between my findings on Nukumanu and those of commentators who have emphasized naturalistic etiologies among the peoples they have studied. In addition to real ethnographic variation, I argue that a major reason for the difference lies in the level of causality (instrumental as opposed to efficient and ultimate) sought by various investigators.

Charting the energy landscape of metal/organic interfaces via machine learning

NASA Astrophysics Data System (ADS)

Scherbela, Michael; Hörmann, Lukas; Jeindl, Andreas; Obersteiner, Veronika; Hofmann, Oliver T.

2018-04-01

The rich polymorphism exhibited by inorganic/organic interfaces is a major challenge for materials design. In this work, we present a method to efficiently explore the potential energy surface and predict the formation energies of polymorphs and defects. This is achieved by training a machine learning model on a list of only 100 candidate structures that are evaluated via dispersion-corrected density functional theory (DFT) calculations. We demonstrate the power of this approach for tetracyanoethylene on Ag(100) and explain the anisotropic ordering that is observed experimentally.

Charting the energy landscape of metal/organic interfaces via machine learning

DOE PAGES

Scherbela, Michael; Hormann, Lukas; Jeindl, Andreas; ...

2018-04-17

The rich polymorphism exhibited by inorganic/organic interfaces is a major challenge for materials design. Here in this work, we present a method to efficiently explore the potential energy surface and predict the formation energies of polymorphs and defects. This is achieved by training a machine learning model on a list of only 100 candidate structures that are evaluated via dispersion-corrected density functional theory (DFT) calculations. Finally, we demonstrate the power of this approach for tetracyanoethylene on Ag(100) and explain the anisotropic ordering that is observed experimentally.

Gene delivery for cancer therapy.

PubMed

Zhang, Teng

2014-01-01

Gene therapy has potential in the treatment of human cancers. However, its clinical implication has only achieved little success due to the lack of an efficient gene delivery system. A major hurdle in the current available approaches is in the ability to transduce target tissues at very high efficiencies that ultimately lead to therapeutic levels of transgene expression. This review outlines the characteristics and utilities of several available gene delivery systems, including their advantages and drawbacks in the context of cancer treatment. A perspective of existing challenges and future directions is also included.

Charting the energy landscape of metal/organic interfaces via machine learning

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

Scherbela, Michael; Hormann, Lukas; Jeindl, Andreas

The rich polymorphism exhibited by inorganic/organic interfaces is a major challenge for materials design. Here in this work, we present a method to efficiently explore the potential energy surface and predict the formation energies of polymorphs and defects. This is achieved by training a machine learning model on a list of only 100 candidate structures that are evaluated via dispersion-corrected density functional theory (DFT) calculations. Finally, we demonstrate the power of this approach for tetracyanoethylene on Ag(100) and explain the anisotropic ordering that is observed experimentally.

Portable non-invasive brain-computer interface: challenges and opportunities of optical modalities

NASA Astrophysics Data System (ADS)

Scholl, Clara A.; Hendrickson, Scott M.; Swett, Bruce A.; Fitch, Michael J.; Walter, Erich C.; McLoughlin, Michael P.; Chevillet, Mark A.; Blodgett, David W.; Hwang, Grace M.

2017-05-01

The development of portable non-invasive brain computer interface technologies with higher spatio-temporal resolution has been motivated by the tremendous success seen with implanted devices. This talk will discuss efforts to overcome several major obstacles to viability including approaches that promise to improve spatial and temporal resolution. Optical approaches in particular will be highlighted and the potential benefits of both Blood-Oxygen Level Dependent (BOLD) and Fast Optical Signal (FOS) will be discussed. Early-stage research into the correlations between neural activity and FOS will be explored.

The Defense Science Board 1997 Summer Study Task Force on DoD Responses to Transnational Threats; Volume 1 - Final Report.

DTIC Science & Technology

1997-10-01

loss of human life - both theirs and ours - their initiatives present a formidable challenge to long-term national security. Even a small nation with...the chemical release killed a dozen people, well over 5,000 were injured and the release had the potential for far more devastating loss of life. In...individuals or groups to produce major damage and loss of life exists today. Events that we have already witnessed could well have resulted in far graver

Understanding Fear of Opportunism in Global Prize-Based Science Contests: Evidence for Gender and Age Differences

PubMed Central

Acar, Oguz Ali; van den Ende, Jan

2015-01-01

Global prize-based science contests have great potential for tapping into diverse knowledge on a global scale and overcoming important scientific challenges. A necessary step for knowledge to be utilized in these contests is for that knowledge to be disclosed. Knowledge disclosure, however, is paradoxical in nature: in order for the value of knowledge to be assessed, inventors must disclose their knowledge, but then the person who receives that knowledge does so at no cost and may use it opportunistically. This risk of potential opportunistic behavior in turn makes the inventor fearful of disclosing knowledge, and this is a major psychological barrier to knowledge disclosure. In this project, we investigated this fear of opportunism in global prize-based science contests by surveying 630 contest participants in the InnoCentive online platform for science contests. We found that participants in these science contests experience fear of opportunism to varying degrees, and that women and older participants have significantly less fear of disclosing their scientific knowledge. Our findings highlight the importance of taking differences in such fears into account when designing global prize-based contests so that the potential of the contests for reaching solutions to important and challenging problems can be used more effectively. PMID:26230086

Molecular markers associated with development and progression of potentially premalignant oral epithelial lesions: Current knowledge and future implications.

PubMed

Nikitakis, Nikolaos G; Pentenero, Monica; Georgaki, Maria; Poh, Catherine F; Peterson, Douglas E; Edwards, Paul; Lingen, Mark; Sauk, John J

2018-06-01

Identification and management of potentially premalignant oral epithelial lesions (PPOELs) at highest risk of malignant transformation holds great promise for successful secondary prevention of oral squamous cell carcinoma, potentially reducing oral cancer morbidity and mortality. However, to date, neither clinical nor histopathologic validated risk predictors that can reliably predict which PPOELs will definitively progress to malignancy have been identified. In addition, the management of PPOELs remains a major challenge. Arguably, progress in the prevention and treatment of oral premalignancy and cancer will require improved understanding of the underlying molecular mechanisms, facilitating the discovery of diagnostic, prognostic, and predictive markers, as well as the identification of novel targeted therapeutics. This review provides a synopsis of the molecular biomarkers that have been studied in PPOELs and have been correlated with the presence and grade of dysplasia and/or their propensity to undergo malignant transformation to oral squamous cell carcinoma. The emphasis is on highlighting new emerging research fields, particularly epigenetic events, including methylation and micro-RNA regulation. Several promising biomarkers are highlighted. Current limitations and challenges are discussed. Recommendations for future focused research areas, to validate and promote clinically useful applications, are offered. Copyright © 2018 Elsevier Inc. All rights reserved.

Mental health consequences of international migration for Vietnamese Americans and the mediating effects of physical health and social networks: results from a natural experiment approach.

PubMed

Fu, Hongyun; VanLandingham, Mark J

2012-05-01

Although the existing literature on immigrant mental health is extensive, major substantive and methodological gaps remain. Substantively, there is little population-based research that focuses on the mental health consequences of migration for Vietnamese Americans. More generally, although a wide range of mental health problems among immigrants has been identified, the potential causal or mediating mechanisms underlying these problems remain elusive. This latter substantive shortcoming is related to a key methodological challenge involving the potentially confounding effects of selection on migration-related outcomes. This article addresses these challenges by employing a "natural experiment" design, involving comparisons among three population-based samples of Vietnamese immigrants, never-leavers, and returnees (N=709). Data were collected in Ho Chi Minh City and in New Orleans between 2003 and 2005. The study investigates the long-term impact of international migration on Vietnamese mental health, and the potential mediating effects of social networks and physical health on these migration-related outcomes. The results reveal both mental health advantages and disadvantages among Vietnamese immigrants relative to the two groups of Vietnamese nationals. Selection can be ruled out for some of these differences, and both social networks and physical health are found to play important explanatory roles.

An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures

PubMed Central

Dugbartey, George J.; Peppone, Luke J.; de Graaf, Inge A.M.

2017-01-01

Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide. PMID:27717837

Understanding Fear of Opportunism in Global Prize-Based Science Contests: Evidence for Gender and Age Differences.

PubMed

Acar, Oguz Ali; van den Ende, Jan

2015-01-01

Global prize-based science contests have great potential for tapping into diverse knowledge on a global scale and overcoming important scientific challenges. A necessary step for knowledge to be utilized in these contests is for that knowledge to be disclosed. Knowledge disclosure, however, is paradoxical in nature: in order for the value of knowledge to be assessed, inventors must disclose their knowledge, but then the person who receives that knowledge does so at no cost and may use it opportunistically. This risk of potential opportunistic behavior in turn makes the inventor fearful of disclosing knowledge, and this is a major psychological barrier to knowledge disclosure. In this project, we investigated this fear of opportunism in global prize-based science contests by surveying 630 contest participants in the InnoCentive online platform for science contests. We found that participants in these science contests experience fear of opportunism to varying degrees, and that women and older participants have significantly less fear of disclosing their scientific knowledge. Our findings highlight the importance of taking differences in such fears into account when designing global prize-based contests so that the potential of the contests for reaching solutions to important and challenging problems can be used more effectively.

A comprehensive review of electrocoagulation for water treatment: Potentials and challenges.

PubMed

Moussa, Dina T; El-Naas, Muftah H; Nasser, Mustafa; Al-Marri, Mohammed J

2017-01-15

Electrocoagulation is an effective electrochemical approach for the treatment of different types of contaminated water and has received considerable attention in recent years due its high efficiency in dealing with numerous stubborn pollutants. It has been successful in dealing with organic and inorganic contaminants with negligible or almost no generation of by-product wastes. During the past decade, vast amount of research has been devoted to utilizing electrocoagulation for the treatment of several types of wastewater, ranging from polluted groundwater to highly contaminated refinery wastewater. This paper offers a comprehensive review of recent literature that has been dedicated to utilizing electrocoagulation for water treatment, focusing on current successes on specific applications in water and wastewater treatment, as well as potentials for future applications. The paper examines such aspects as theory, potential applications, current challenges, recent developments as well as economical concerns associated with the technology. Most of the recent EC research has been focusing on pollutant-specific evaluation without paying attention to cell design, process modeling or industrial applications. This review attempts to highlight the main achievements in the area and outlines the major shortcomings with recommendations for promising research options that can enhance the technology and broaden its range of applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular dynamics for near melting temperatures simulations of metals using modified embedded-atom method

NASA Astrophysics Data System (ADS)

Etesami, S. Alireza; Asadi, Ebrahim

2018-01-01

Availability of a reliable interatomic potential is one of the major challenges in utilizing molecular dynamics (MD) for simulations of metals at near the melting temperatures and melting point (MP). Here, we propose a novel approach to address this challenge in the concept of modified-embedded-atom (MEAM) interatomic potential; also, we apply the approach on iron, nickel, copper, and aluminum as case studies. We propose adding experimentally available high temperature elastic constants and MP of the element to the list of typical low temperature properties used for the development of MD interatomic potential parameters. We show that the proposed approach results in a reasonable agreement between the MD calculations of melting properties such as latent heat, expansion in melting, liquid structure factor, and solid-liquid interface stiffness and their experimental/computational counterparts. Then, we present the physical properties of mentioned elements near melting temperatures using the new MEAM parameters. We observe that the behavior of elastic constants, heat capacity and thermal linear expansion coefficient at room temperature compared to MP follows an empirical linear relation (α±β × MP) for transition metals. Furthermore, a linear relation between the tetragonal shear modulus and the enthalpy change from room temperature to MP is observed for face-centered cubic materials.

Reducing Disparities through Culturally Competent Health Care: An Analysis of the Business Case

PubMed Central

Brach, Cindy; Fraser, Irene

2016-01-01

Finding ways to deliver high-quality health care to an increasingly diverse population is a major challenge for the American health care system. The persistence of racial and ethnic disparities in health care access, quality, and outcomes has prompted considerable interest in increasing the cultural competence of health care, both as an end in its own right and as a potential means to reduce disparities. This article reviews the potential role of cultural competence in reducing racial and ethnic health disparities, the strength of health care organizations’ current incentives to adopt cultural competence techniques, and the limitations inherent in these incentives that will need to be overcome if cultural competence techniques are to become widely adopted. PMID:12938253

Greater Severity of Peanut Challenge Reactions Using a High fat versus Low Fat Matrix Vehicle.

PubMed

Pettersson, M Eleonore; Koppelman, Gerard H; Schins, Afke M M; van Ginkel, C Doriene; Flokstra-de Blok, Bertine M J; Kollen, Boudewijn J; Dubois, Anthony E J

2018-06-16

Food allergy is a potentially life-threatening disease with a detrimental effect on the quality of life of caregivers and children.(1) Although many different types of food have been identified as potential elicitors of allergic reactions, only a small number of these foods cause the majority of reactions.(2) Food consists of a complex mixture of nutrient and non-nutrient components and their molecular interactions, which are known as the food matrix. Individual matrix components, or the matrix as a whole, may interact with a food allergen and may influence the clinical response to that allergen. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Structured prediction models for RNN based sequence labeling in clinical text.

PubMed

Jagannatha, Abhyuday N; Yu, Hong

2016-11-01

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies for structured prediction in order to improve the exact phrase detection of various medical entities.

Structured prediction models for RNN based sequence labeling in clinical text

PubMed Central

Jagannatha, Abhyuday N; Yu, Hong

2016-01-01

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies1 for structured prediction in order to improve the exact phrase detection of various medical entities. PMID:28004040

Challenges of using electrical resistivity method to locate karst conduits-A field case in the Inner Bluegrass Region, Kentucky

USGS Publications Warehouse

Zhu, J.; Currens, J.C.; Dinger, J.S.

2011-01-01

Conduits serve as major pathways for groundwater flow in karst aquifers. Locating them from the surface, however, is one of the most challenging tasks in karst research. Geophysical methods are often deployed to help locate voids by mapping variations of physical properties of the subsurface. Conduits can cause significant contrasts of some physical properties that can be detected; other subsurface features such as water-bearing fractures often yield similar contrasts, which are difficult to distinguish from the effects of the conduits. This study used electrical resistivity method to search for an unmapped karst conduit that recharges Royal Spring in the Inner Bluegrass karst region, Kentucky, USA. Three types of resistivity techniques (surface 2D survey, quasi-3D survey, and time-lapse survey) were used to map and characterize resistivity anomalies. Some of the major anomalies were selected as drilling targets to verify the existence of the conduits. Drilling near an anomaly identified by an electrical resistivity profile resulted in successful penetration of a major water-filled conduit. The drilling results also suggest that, in this study area, low resistivity anomalies in general are associated with water-bearing features. However, differences in the anomaly signals between the water-filled conduit and other water-bearing features such as water-filled fracture zones were undistinguishable. The electrical resistivity method is useful in conduit detection by providing potential drilling targets. Knowledge of geology and hydrogeology about the site and professional judgment also played important roles in locating the major conduit. ?? 2011 Elsevier B.V.

Pedophiles and stalkers as transplant candidates: one program's experience.

PubMed

Paris, Wayne; Miller, Rachel; Hille, Cheryl; Nour, Bakr; Griggs, Johnny

2005-12-01

Transplant assessment of pedophiles and stalkers presents a challenge for clinicians and requires the ability to separate the science from the hysteria. Although rarely seen in organ transplant clinics, the presence of psychosexual disorders can result in both criminal charges and harsh societal reactions. Clinicians must be able to assess and make informed recommendations about the suitability of the candidate and any potential risks for staff, other patients, and society at large. Six patients (5 pedophiles and 1 stalker) were assessed at our major regional multiorgan transplant program; each patient presented with unique and challenging assessment, treatment, and selection issues for the transplant team. The objectives of this article are to raise awareness of the issues associated with pedophiles and stalkers, and to provide the basis for better-informed discussions based on one program's struggles with its candidate selection and follow-up.

Resources, challenges and way forward in rare mitochondrial diseases research.

PubMed

Rajput, Neeraj Kumar; Singh, Vipin; Bhardwaj, Anshu

2015-01-01

Over 300 million people are affected by about 7000 rare diseases globally. There are tremendous resource limitations and challenges in driving research and drug development for rare diseases. Hence, innovative approaches are needed to identify potential solutions. This review focuses on the resources developed over the past years for analysis of genome data towards understanding disease biology especially in the context of mitochondrial diseases, given that mitochondria are central to major cellular pathways and their dysfunction leads to a broad spectrum of diseases. Platforms for collaboration of research groups, clinicians and patients and the advantages of community collaborative efforts in addressing rare diseases are also discussed. The review also describes crowdsourcing and crowdfunding efforts in rare diseases research and how the upcoming initiatives for understanding disease biology including analyses of large number of genomes are also applicable to rare diseases.

Exosome levels in human body fluids: A tumor marker by themselves?

PubMed

Cappello, Francesco; Logozzi, Mariantonia; Campanella, Claudia; Bavisotto, Celeste Caruso; Marcilla, Antonio; Properzi, Francesca; Fais, Stefano

2017-01-01

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can provide several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may themselves represent a predictive/diagnostic of tumors, discriminating cancer patients from healthy subjects. The aim of this review is to highlight these latest challenging findings to provide novel and groundbreaking ideas for successful tumor early diagnosis and follow-up. Copyright © 2016 Elsevier B.V. All rights reserved.

In Vitro Evaluation of Molecular Tumor Targets in Nuclear Medicine: Immunohistochemistry Is One Option, but Under Which Conditions?

PubMed

Reubi, Jean Claude

2017-12-01

The identification of new molecular targets for diagnostic and therapeutic applications using in vitro methods is an important challenge in nuclear medicine. One such method is immunohistochemistry, increasingly popular because it is easy to perform. This review presents the case for conducting receptor immunohistochemistry to evaluate potential molecular targets in human tumor tissue sections. The focus is on the immunohistochemistry of G-protein-coupled receptors, one of the largest families of cell surface proteins, representing a major class of drug targets and thus playing an important role in nuclear medicine. This review identifies common pitfalls and challenges and provides guidelines on performing such immunohistochemical studies. An appropriate validation of the target is a prerequisite for developing robust and informative new molecular probes. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

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

PubMed Central

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

2016-01-01

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

Mix-and-diffuse serial synchrotron crystallography

DOE PAGES

Beyerlein, Kenneth R.; Dierksmeyer, Dennis; Mariani, Valerio; ...

2017-10-09

Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzymemore » at a high level of detail. Here, the success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.« less

Mix-and-diffuse serial synchrotron crystallography

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

Beyerlein, Kenneth R.; Dierksmeyer, Dennis; Mariani, Valerio

Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzymemore » at a high level of detail. Here, the success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.« less

The High-Luminosity upgrade of the LHC: Physics and Technology Challenges for the Accelerator and the Experiments

NASA Astrophysics Data System (ADS)

Schmidt, Burkhard

2016-04-01

In the second phase of the LHC physics program, the accelerator will provide an additional integrated luminosity of about 2500/fb over 10 years of operation to the general purpose detectors ATLAS and CMS. This will substantially enlarge the mass reach in the search for new particles and will also greatly extend the potential to study the properties of the Higgs boson discovered at the LHC in 2012. In order to meet the experimental challenges of unprecedented pp luminosity, the experiments will need to address the aging of the present detectors and to improve the ability to isolate and precisely measure the products of the most interesting collisions. The lectures gave an overview of the physics motivation and described the conceptual designs and the expected performance of the upgrades of the four major experiments, ALICE, ATLAS, CMS and LHCb, along with the plans to develop the appropriate experimental techniques and a brief overview of the accelerator upgrade. Only some key points of the upgrade program of the four major experiments are discussed in this report; more information can be found in the references given at the end.

The Immunological Challenges of Cell Transplantation for the Treatment of Parkinson’s Disease

PubMed Central

Piquet, Amanda L.; Venkiteswaran, Kala; Marupudi, Neena I.; Berk, Matthew; Subramanian, Thyagarajan

2012-01-01

Dopaminergic cell transplantation is an experimental therapy for Parkinson’s disease (PD). It has many potential theoretical advantages over current treatment strategies such as providing continuous local dopaminergic replenishment, eliminating motor fluctuations and medication-induced dyskinesias, slowing down disease progression or even reversing disease pathology in the host. Recent studies also show that dopaminergic cell transplants provide long-term neuromodulation in the basal ganglia that simulates the combined effects of oral dopaminergic therapy and surgical therapies like deep brain stimulation, the contemporary therapeutic approach to advanced PD. However, dopaminergic cell transplantation in PD as not been optimized and current experimental techniques have many drawbacks. In published experiments to date of attempted dopaminergic grafting in PD, the major challenges are unacceptable graft-induced dyskinesias or failure of such grafts to exceed the benefits afforded by sham surgery. A deleterious host immune response to the transplant has been implicated as a major putative cause for these adverse outcomes. This article focuses on recent advances in understanding the immunology of the transplantation in PD and possible methods to overcome adverse events such that we could translate cell replacement strategies into viable clinical treatments in the future. PMID:22521427

The Microbiome and Sustainable Healthcare

PubMed Central

Dietert, Rodney R.; Dietert, Janice M.

2015-01-01

Increasing prevalences, morbidity, premature mortality and medical needs associated with non-communicable diseases and conditions (NCDs) have reached epidemic proportions and placed a major drain on healthcare systems and global economies. Added to this are the challenges presented by overuse of antibiotics and increased antibiotic resistance. Solutions are needed that can address the challenges of NCDs and increasing antibiotic resistance, maximize preventative measures, and balance healthcare needs with available services and economic realities. Microbiome management including microbiota seeding, feeding, and rebiosis appears likely to be a core component of a path toward sustainable healthcare. Recent findings indicate that: (1) humans are mostly microbial (in terms of numbers of cells and genes); (2) immune dysfunction and misregulated inflammation are pivotal in the majority of NCDs; (3) microbiome status affects early immune education and risk of NCDs, and (4) microbiome status affects the risk of certain infections. Management of the microbiome to reduce later-life health risk and/or to treat emerging NCDs, to spare antibiotic use and to reduce the risk of recurrent infections may provide a more effective healthcare strategy across the life course particularly when a personalized medicine approach is considered. This review will examine the potential for microbiome management to contribute to sustainable healthcare. PMID:27417751

The immunological challenges of cell transplantation for the treatment of Parkinson's disease.

PubMed

Piquet, Amanda L; Venkiteswaran, Kala; Marupudi, Neena I; Berk, Matthew; Subramanian, Thyagarajan

2012-07-01

Dopaminergic cell transplantation is an experimental therapy for Parkinson's disease (PD). It has many potential theoretical advantages over current treatment strategies such as providing continuous local dopaminergic replenishment, eliminating motor fluctuations and medication-induced dyskinesias, slowing down disease progression or even reversing disease pathology in the host. Recent studies also show that dopaminergic cell transplants provide long-term neuromodulation in the basal ganglia that simulates the combined effects of oral dopaminergic therapy and surgical therapies like deep brain stimulation, the contemporary therapeutic approach to advanced PD. However, dopaminergic cell transplantation in PD as not been optimized and current experimental techniques have many drawbacks. In published experiments to date of attempted dopaminergic grafting in PD, the major challenges are unacceptable graft-induced dyskinesias or failure of such grafts to exceed the benefits afforded by sham surgery. A deleterious host immune response to the transplant has been implicated as a major putative cause for these adverse outcomes. This article focuses on recent advances in understanding the immunology of the transplantation in PD and possible methods to overcome adverse events such that we could translate cell replacement strategies into viable clinical treatments in the future. Copyright © 2012 Elsevier Inc. All rights reserved.

Challenges in engineering osteochondral tissue grafts with hierarchical structures.

PubMed

Gadjanski, Ivana; Vunjak-Novakovic, Gordana

2015-01-01

A major hurdle in treating osteochondral (OC) defects is the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens and harnessing of inflammatory responses of the host will likely drive the further progress.

Tiger in the fault tree jungle

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

Rubel, P.

1976-01-01

There is yet little evidence of serious efforts to apply formal reliability analysis methods to evaluate, or even to identify, potential common-mode failures (CMF) of reactor safeguard systems. The prospects for event logic modeling in this regard are examined by the primitive device of reviewing actual CMF experience in terms of what the analyst might have perceived a priori. Further insights of the probability and risks aspects of CMFs are sought through consideration of three key likelihood factors: (1) prior probability of cause ever existing, (2) opportunities for removing cause, and (3) probability that a CMF cause will be activatedmore » by conditions associated with a real system challenge. It was concluded that the principal needs for formal logical discipline in the endeavor to decrease CMF-related risks are to discover and to account for strong ''energetic'' dependency couplings that could arise in the major accidents usually classed as ''hypothetical.'' This application would help focus research, design and quality assurance efforts to cope with major CMF causes. But without extraordinary challenges to the reactor safeguard systems, there must continue to be virtually no statistical evidence pertinent to that class of failure dependencies.« less

Challenges and Ideas from a Research Program on High Quality, Evidence-Based Practice in School Mental Health

PubMed Central

Weist, Mark D.; Youngstrom, Eric A.; Stephan, Sharon; Lever, Nancy; Fowler, Johnathan; Taylor, Leslie; McDaniel, Heather; Chappelle, Lori; Paggeot, Samantha; Hoagwood, Kimberly

2013-01-01

Objective Reviews the progression of a research program designed to develop, implement and study the implementation of “achievable” evidence-based practices (EBPs) in schools. Reviews challenges encountered and ideas to overcome them to enhance this avenue of research. Method Presents two federally funded randomized controlled trials involving comparison of a four-component targeted intervention (Quality Assessment and Improvement, Family Engagement and Empowerment, Modular Evidence-Based Practice, Implementation Support) versus a comparison intervention focused on Personal Wellness. In both studies primary aims focused on changes in clinician attitudes and behavior, including the delivery of high quality, evidence-based practices and secondary aims focused on student level impacts. Results A number of challenges, many not reported in the literature are reviewed, and ideas for overcoming them are presented. Conclusions Given the reality that the majority of youth mental health services are delivered in schools and the potential of school mental health (SMH) services to provide a continuum of mental health care from promotion to intervention, it is critical that the field consider and address the logistical and methodological challenges associated with implementing and studying EBP implementation by clinicians. PMID:24063310

Challenges and ideas from a research program on high-quality, evidence-based practice in school mental health.

PubMed

Weist, Mark D; Youngstrom, Eric A; Stephan, Sharon; Lever, Nancy; Fowler, Johnathan; Taylor, Leslie; McDaniel, Heather; Chappelle, Lori; Paggeot, Samantha; Hoagwood, Kimberly

2014-01-01

This article reviews the progression of a research program designed to develop, implement, and study the implementation of "achievable" evidence-based practices (EBPs) in schools. We review challenges encountered and ideas to overcome them to enhance this avenue of research. The article presents two federally funded randomized controlled trials involving comparison of a four-component targeted intervention (Quality Assessment and Improvement, Family Engagement and Empowerment, Modular Evidence-Based Practice, Implementation Support) versus a comparison intervention focused on personal wellness. In both studies, primary aims focused on changes in clinician attitudes and behavior, including the delivery of high-quality EBPs and secondary aims focused on student-level impacts. A number of challenges, many not reported in the literature, are reviewed, and ideas for overcoming them are presented. Given the reality that the majority of youth mental health services are delivered in schools and the potential of school mental health services to provide a continuum of mental health care from promotion to intervention, it is critical that the field consider and address the logistical and methodological challenges associated with implementing and studying EBP implementation by clinicians.

Implementation of the Integrated Management of Childhood Illnesses strategy: challenges and recommendations in Botswana

PubMed Central

Mupara, Lucia U.; Lubbe, Johanna C.

2016-01-01

Background Under-five mortality has been a major public health challenge from time immemorial. In response to this challenge, the World Health Organization and the United Nations Children's Fund developed the Integrated Management of Childhood Illnesses (IMCI) strategy and presented it to the whole world as a key approach to reduce child morbidity and mortality. Botswana started to implement the IMCI strategy in 1998. Reductions in the under-five mortality rate (U5MR) have been documented, although the reduction is not on par with the expected Millennium Development Goal 4 predictions. Design A quantitative study was done to identify the problems IMCI implementers face when tending children under 5 years in the Gaborone Health District of Botswana. The study population was made up of all the IMCI-trained and registered nurses, and systematic sampling was used to randomly select study participants. Questionnaires were used to collect data. Results The study findings indicated challenges related to low training coverage, health systems, and the unique features of the IMCI strategy. Conclusions The comprehensive implementation of the IMCI strategy has the potential to significantly influence the U5MR in Botswana. PMID:26899774

Physics, Physicists and Revolutionary Capabilities for the Intelligence Community

NASA Astrophysics Data System (ADS)

Porter, Lisa

2009-05-01

Over the past several decades, physicists have made seminal contributions to technological capabilities that have enabled the U.S. intelligence community to provide unexpected and unparalleled information to our nation's decision makers and help dispel the cloud of uncertainty they face in dealing with crises and challenges around the world. As we look to the future, we recognize that the ever-quickening pace of changes in the world and the threats we must confront demand continued innovation and improvement in the capabilities needed to provide the information on which our leaders depend. This talk will focus on some of the major technological challenges that the intelligence community faces in the coming years, and the many ways that physicists can help to overcome those challenges. The potential impact of physicists on the future capabilities of the US intelligence community is huge. In addition to the more obvious and direct impact through research in areas ranging from novel sensors to quantum information science, the unique approach physicists bring to a problem can also have an indirect but important effect by influencing how challenges in areas ranging from cybersecurity to advanced analytics are approached and solved. Several examples will be given.

A recombinant fowl adenovirus expressing the S1 gene of infectious bronchitis virus protects against challenge with infectious bronchitis virus.

PubMed

Johnson, Michael A; Pooley, Catherine; Ignjatovic, Jagoda; Tyack, Scott G

2003-06-20

The spike peplomer S1 subunit sequence from avian infectious bronchitis virus (IBV) Vic S strain was expressed in a plasmid under the control of the fowl adenovirus (FAV) major late promoter (MLP). Two recombinants were constructed in FAV serotype 8 (FAV 8) by inserting the expression cassette between the SnaBI and XbaI restriction enzyme sites (clone DA3) or between the SpeI sites (clone CA6-20). Expression of the S1 gene in the recombinants was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) by 20h post-infection. Commercial broiler chickens were orally vaccinated at day 0 or day 6 post-hatch and challenged at day 35 post-hatch. FAV antibody ELISA confirmed that maternal antibody directed against inclusion body hepatitis (serotype 8) had decayed in control birds and that FAV specific serum IgG responses were produced in vaccinated birds at the time of challenge. Further, an S1 specific antibody response was detected prior to challenge. Birds were challenged with either Vic S (serotype B) or N1/62 (serotype C) strains of IBV. The tracheas of challenged birds were analyzed by RT-PCR and re-isolation of virus. In birds vaccinated at day 6, 90-100% protection at the trachea was induced against either homologous or heterologous challenge. The construction of a recombinant FAV expressing S1 of IBV demonstrates the potential of an alternative vaccination strategy against IBV.

Leadership challenges in multinational medical peacekeeping operations: Lessons from UNIFIL Hospital.

PubMed

Datta, Rakesh; Khanna, Sangeeta

2017-10-01

Commanding a military multinational and multilingual healthcare facility can be a formidable task with very little margin for error. The authors were in leadership positions of UNIFIL Hospital, unique in its diversity of both staff and clientele. Experience about the challenges faced and methods adopted to overcome them will be shared. Troops from diverse backgrounds differ in their competency, and also in their attitudinal approach to situations. It is imperative for the medical commanders to identify these differences, and work towards harnessing individual strengths to form a cohesive unit. Frequent rotation of team members and thereby difficulty in adapting to new environment makes the tasks more challenging. Challenges can be broadly categorized in those dealing with functional roles (providing medical support) and command and control issues. Linguistic challenges especially in situations where professionals have to work as a coordinated unit remains a major challenge. The threat of medical errors arising out of misunderstandings is very real. Gender sensitization is essential to avoid potential unpleasant situations. Interpersonal conflict can easily go out of hand. The leadership has to be more direct and deliberate relying less on hierarchy and more on direct communication. A strict enforcement of UN standards for equipment and competence, frequent joint medical drills help to overcome interoperability issues and develop mutual confidence. Leadership in multinational UN hospitals is a demanding task with its peculiar set of challenges. A systematic and deliberate approach focused on mutual respect, flexibility and direct leadership can help medical commanders in such situations.

The future of the Amazon: new perspectives from climate, ecosystem and social sciences.

PubMed

Betts, Richard A; Malhi, Yadvinder; Roberts, J Timmons

2008-05-27

The potential loss or large-scale degradation of the tropical rainforests has become one of the iconic images of the impacts of twenty-first century environmental change and may be one of our century's most profound legacies. In the Amazon region, the direct threat of deforestation and degradation is now strongly intertwined with an indirect challenge we are just beginning to understand: the possibility of substantial regional drought driven by global climate change. The Amazon region hosts more than half of the world's remaining tropical forests, and some parts have among the greatest concentrations of biodiversity found anywhere on Earth. Overall, the region is estimated to host about a quarter of all global biodiversity. It acts as one of the major 'flywheels' of global climate, transpiring water and generating clouds, affecting atmospheric circulation across continents and hemispheres, and storing substantial reserves of biomass and soil carbon. Hence, the ongoing degradation of Amazonia is a threat to local climate stability and a contributor to the global atmospheric climate change crisis. Conversely, the stabilization of Amazonian deforestation and degradation would be an opportunity for local adaptation to climate change, as well as a potential global contributor towards mitigation of climate change. However, addressing deforestation in the Amazon raises substantial challenges in policy, governance, sustainability and economic science. This paper introduces a theme issue dedicated to a multidisciplinary analysis of these challenges.

CD62L− memory T cells enhance T-cell regeneration after allogeneic stem cell transplantation by eliminating host resistance in mice

PubMed Central

Zhang, Jifeng; Barefoot, Brice E.; Mo, Wenjian; Deoliveira, Divino; Son, Jessica; Cui, Xiuyu; Ramsburg, Elizabeth

2012-01-01

A major challenge in allogeneic hematopoietic cell transplantation is how to transfer T-cell immunity without causing graft-versus-host disease (GVHD). Effector memory T cells (CD62L−) are a cell subset that can potentially address this challenge because they do not induce GVHD. Here, we investigated how CD62L− T cells contributed to phenotypic and functional T-cell reconstitution after transplantation. On transfer into allogeneic recipients, CD62L− T cells were activated and expressed multiple cytokines and cytotoxic molecules. CD62L− T cells were able to deplete host radioresistant T cells and facilitate hematopoietic engraftment, resulting in enhanced de novo T-cell regeneration. Enhanced functional immune reconstitution was demonstrated in CD62L− T-cell recipients using a tumor and an influenza virus challenge model. Even though CD62L− T cells are able to respond to alloantigens and deplete host radioresistant immune cells in GVHD recipients, alloreactive CD62L− T cells lost the reactivity over time and were eventually tolerant to alloantigens as a result of prolonged antigen exposure, suggesting a mechanism by which CD62L− T cells were able to eliminate host resistance without causing GVHD. These data further highlight the unique characteristics of CD62L− T cells and their potential applications in clinical hematopoietic cell transplantation. PMID:22596261

Women's decision to major in STEM fields

NASA Astrophysics Data System (ADS)

Conklin, Stephanie

This paper explores the lived experiences of high school female students who choose to enter into STEM fields, and describes the influencing factors which steered these women towards majors in computer science, engineering and biology. Utilizing phenomenological methodology, this study seeks to understand the essence of women's decisions to enter into STEM fields and further describe how the decision-making process varies for women in high female enrollment fields, like biology, as compared with low enrollment fields like, computer science and engineering. Using Bloom's 3-Stage Theory, this study analyzes how relationships, experiences and barriers influenced women towards, and possibly away, from STEM fields. An analysis of women's experiences highlight that support of family, sustained experience in a STEM program during high school as well as the presence of an influential teacher were all salient factors in steering women towards STEM fields. Participants explained that influential teacher worked individually with them, modified and extended assignments and also steered participants towards coursework and experiences. This study also identifies factors, like guidance counselors as well as personal challenges, which inhibited participant's path to STEM fields. Further, through analyzing all six participants' experiences, it is clear that a linear model, like Bloom's 3-Stage Model, with limited ability to include potential barriers inhibited the ability to capture the essence of each participant's decision-making process. Therefore, a revised model with no linear progression which allows for emerging factors, like personal challenges, has been proposed; this model focuses on how interest in STEM fields begins to develop and is honed and then mastered. This study also sought to identify key differences in the paths of female students pursuing different majors. The findings of this study suggest that the path to computer science and engineering is limited. Computer science majors faced few, if any, challenges, hoped to use computers as a tool to innovate and also participated in the same computer science program. For female engineering students, the essence of their experience focused on interaction at a young age with an expert in an engineering-related field as well as a strong desire to help solve world problems using engineering. These participants were able to articulate clearly future careers. In contrast, biology majors, faced more challenges and were undecided about their future career goals. These results suggest that a longitudinal study focused on women pursuing engineering and computer science fields is warranted; this will hopefully allow these findings to be substantiated and also for refinement of the revised theoretical model.

Challenges of coverage policy development for next-generation tumor sequencing panels: experts and payers weigh in.

PubMed

Trosman, Julia R; Weldon, Christine B; Kelley, R Kate; Phillips, Kathryn A

2015-03-01

Next-generation tumor sequencing (NGTS) panels, which include multiple established and novel targets across cancers, are emerging in oncology practice, but lack formal positive coverage by US payers. Lack of coverage may impact access and adoption. This study identified challenges of NGTS coverage by private payers. We conducted semi-structured interviews with 14 NGTS experts on potential NGTS benefits, and with 10 major payers, representing more than 125,000,000 enrollees, on NGTS coverage considerations. We used the framework approach of qualitative research for study design and thematic analyses and simple frequencies to further describe findings. All interviewed payers see potential NGTS benefits, but all noted challenges to formal coverage: 80% state that inherent features of NGTS do not fit the medical necessity definition required for coverage, 70% view NGTS as a bundle of targets versus comprehensive tumor characterization and may evaluate each target individually, and 70% express skepticism regarding new evidence methods proposed for NGTS. Fifty percent of payers expressed sufficient concerns about NGTS adoption and implementation that will preclude their ability to issue positive coverage policies. Payers perceive that NGTS holds significant promise but, in its current form, poses disruptive challenges to coverage policy frameworks. Proactive multidisciplinary efforts to define the direction for NGTS development, evidence generation, and incorporation into coverage policy are necessary to realize its promise and provide patient access. This study contributes to current literature, as possibly the first study to directly interview US payers on NGTS coverage and reimbursement. Copyright © 2015 by the National Comprehensive Cancer Network.

Challenges of Coverage Policy Development for Next-Generation Tumor Sequencing Panels: Experts and Payers Weigh In

PubMed Central

Trosman, Julia R.; Weldon, Christine B.; Kate Kelley, R.; Phillips, Kathryn A.

2015-01-01

Background Next-generation tumor sequencing (NGTS) panels, which include multiple established and novel targets across cancers, are emerging in oncology practice, but lack formal positive coverage by US payers. Lack of coverage may impact access and adoption. This study identified challenges of NGTS coverage by private payers. Methods We conducted semi-structured interviews with 14 NGTS experts on potential NGTS benefits, and with 10 major payers, representing more than 125,000,000 enrollees, on NGTS coverage considerations. We used the framework approach of qualitative research for study design and thematic analyses and simple frequencies to further describe findings. Results All interviewed payers see potential NGTS benefits, but all noted challenges to formal coverage: 80% state that inherent features of NGTS do not fit the medical necessity definition required for coverage, 70% view NGTS as a bundle of targets versus comprehensive tumor characterization and may evaluate each target individually, and 70% express skepticism regarding new evidence methods proposed for NGTS. Fifty percent of payers expressed sufficient concerns about NGTS adoption and implementation that will preclude their ability to issue positive coverage policies. Conclusions Payers perceive that NGTS holds significant promise but, in its current form, poses disruptive challenges to coverage policy frameworks. Proactive multidisciplinary efforts to define the direction for NGTS development, evidence generation, and incorporation into coverage policy are necessary to realize its promise and provide patient access. This study contributes to current literature, as possibly the first study to directly interview US payers on NGTS coverage and reimbursement. PMID:25736008

Qualitative Analysis of Round-Table Discussions on the Business Case and Procurement Challenges for Hospital Electronic Prescribing Systems

PubMed Central

Cresswell, Kathrin M.; Slee, Ann; Coleman, Jamie; Williams, Robin; Bates, David W.; Sheikh, Aziz

2013-01-01

Objectives There is a pressing need to understand the challenges surrounding procurement of and business case development for hospital electronic prescribing systems, and to identify possible strategies to enhance the efficiency of these processes in order to assist strategic decision making. Materials and Methods We organized eight multi-disciplinary round-table discussions in the United Kingdom. Participants included policy makers, representatives from hospitals, system developers, academics, and patients. Each discussion was digitally audio-recorded, transcribed verbatim and, together with accompanying field notes, analyzed thematically with NVivo9. Results We drew on data from 17 participants (approximately eight per roundtable), six hours of discussion, and 15 pages of field notes. Key challenges included silo planning with systems not being considered as part of an integrated organizational information technology strategy, lack of opportunity for interactions between customers and potential suppliers, lack of support for hospitals in choosing appropriate systems, difficulty of balancing structured planning with flexibility, and the on-going challenge of distinguishing “wants” and aspirations from organizational “needs”. Discussion and conclusions Development of business cases for major investments in information technology does not take place in an organizational vacuum. Building on previously identified potentially transferable dimensions to the development and execution of business cases surrounding measurements of costs/benefits and risk management, we have identified additional components relevant to ePrescribing systems. These include: considerations surrounding strategic context, case for change and objectives, future service requirements and options appraisal, capital and revenue implications, timescale and deliverability, and risk analysis and management. PMID:24260213

Brine production strategy modeling for active and integrated management of water resources in CCS

NASA Astrophysics Data System (ADS)

Court, B.; Celia, M. A.; Nordbotten, J. M.; Buscheck, T. A.; Elliot, T. J.; Bandilla, K.; Dobossy, M.

2010-12-01

Our society is at present highly dependent on coal, which will continue to play a major role in baseload electricity production in the coming decades. Most projected climate change mitigation strategies require CO2 Capture and Sequestration (CCS) as a vital element to stabilize CO2 atmospheric emissions. In these strategies, CCS will have to expand in the next two decades by several orders of magnitude compared to current worldwide implementation. At present the interactions among freshwater extraction, CO2 injection, and brine management are being considered too narrowly across CCS operations, and in the case of freshwater almost completely overlooked. Following the authors’ recently published overview of these challenges, an active and integrated management of water resources throughout CCS operations was proposed to avoid overlooking critical challenges that may become major obstacles to CCS implementation. Water resources management is vital for several reasons including that a coal-fired power plant retrofitted for CCS requires twice as much cooling water as the original plant. However this increased demand may be accommodated by brine extraction and treatment, which would concurrently function as large-scale pressure management and a potential source of freshwater. Synergistic advantages of such proactive integration that were identified led the authors to concluded that: Active management of CCS operations through an integrated approach -including brine production, treatment, use for cooling, and partial reinjection- can address challenges simultaneously with several synergistic advantages; and, that freshwater and brine must be linked to CO2 and pressure as key decision making parameters throughout CCS operations while recognizing scalability and potential pore space competition challenges. This work presents a detailed modeling investigation of a potential integration opportunity resulting from brine production. Technical results will focus solely on the conjunctive use of saline aquifers for CO2 sequestration and water supply for power plants. The impact of CO2 injection-brine withdrawal coupling on (i) the CO2 injection plume, (ii) the pressure field, and (iii) CO2 and brine leakage risk will be quantified using a range of simulation codes from Schlumberger’s full numerical ECLIPSE model to a simplified analytical model, in an effort to complement useful work initiated at Lawrence Livermore National Laboratory. In particular the impact of different relative permeability and capillary pressure curves on these three components will be presented and put in context of current modeling risk analysis approach in the CCS scientific community.

Blood donors in Kenya: a comparison of voluntary and family replacement donors based on a population-based survey.

PubMed

Kimani, D; Mwangi, J; Mwangi, M; Bunnell, R; Kellogg, T A; Oluoch, T; Gichangi, A; Kaiser, R; Mugo, N; Odongo, T; Oduor, M; Marum, L

2011-02-01

Blood safety and sufficiency are major challenges in Kenya and other sub-Saharan African countries forcing many countries to rely on family replacement donors (FRD). We analysed data from a national AIDS indicator survey to describe blood donors in Kenya and potential risks of transfusion transmissible infections (TTI) comparing voluntary donors and FRD. A population-based, cross-sectional survey was conducted in 2007 among 15- to 64-year-olds. Consenting participants were interviewed about blood donation history and were tested for HIV, HSV-2 and syphilis. Of the 17,940 people surveyed, 445 (2·3%) reported donating blood in the prior 12 months. Sixty-four per cent were voluntary donors, and the rest were FRD. Compared to FRD, the majority of voluntary donors were <25 years old (59% versus 18%), from the highest wealth quintile (57% versus 42%) and single (64% versus 23%). In addition, voluntary donors were less likely to have been sexually active than replacement donors (43% versus 13%). HIV prevalence was lower among voluntary donors than among FRD (2·6% versus 7·4%, P-value=0·07). The majority of blood donors in Kenya are voluntary with lower potential risk of TTI. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery.

PubMed

Yang, Qi; Parker, Christina L; McCallen, Justin D; Lai, Samuel K

2015-12-28

Tumors are frequently characterized by genomically and phenotypically distinct cancer cell subpopulations within the same tumor or between tumor lesions, a phenomenon termed tumor heterogeneity. These diverse cancer cell populations pose a major challenge to targeted delivery of diagnostic and/or therapeutic agents, as the conventional approach of conjugating individual ligands to nanoparticles is often unable to facilitate intracellular delivery to the full spectrum of cancer cells present in a given tumor lesion or patient. As a result, many cancers are only partially suppressed, leading to eventual tumor regrowth and/or the development of drug-resistant tumors. Pretargeting (multistep targeting) approaches involving the administration of 1) a cocktail of bispecific proteins that can collectively bind to the entirety of a mixed tumor population followed by 2) nanoparticles containing therapeutic and/or diagnostic agents that can bind to the bispecific proteins accumulated on the surface of target cells offer the potential to overcome many of the challenges associated with drug delivery to heterogeneous tumors. Despite its considerable success in improving the efficacy of radioimmunotherapy, the pretargeting strategy remains underexplored for a majority of nanoparticle therapeutic applications, especially for targeted delivery to heterogeneous tumors. In this review, we will present concepts in tumor heterogeneity, the shortcomings of conventional targeted systems, lessons learned from pretargeted radioimmunotherapy, and important considerations for harnessing the pretargeting strategy to improve nanoparticle delivery to heterogeneous tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

[Changing economic environment of hospitals: management challenges of the 1990s].

PubMed

Rotstein, Z; Noy, S; Goldman, B; Shani, M

1990-12-16

The modern hospital is an organization which is influenced by the external environment in which it functions. A major relevant area is the economic environment. In recent years the western world has been facing the challenge of rising costs of health care and an increase in their proportion to the gross national product of most countries. Consequently, hospitals as major providers of health care are under pressure from governments and health insurance companies to cut costs and to "produce" more efficiently. Since hospitals worldwide are finding it hard and painful to function in the new environment in which attitudes to hospitals are changing, a potential managerial-economic crisis may be the next phase. How can the hospital adapt to these changes? First, by adopting managerial attitudes and the tools of the business sector. These include: the strategic planning process, hospital operative autonomy, creating medical-economic responsibility centers as departments, cost-accounting for medical procedures, and case-mix budgeting. Management information systems are necessary during the transition. The hospital information system should include functions at the operative level, such as outpatient visits, and admissions and discharges of patients; and also clinical, diagnostic and laboratory procedures related to the patient case-mix. The second level is a management information system which includes salaries of personnel, case-mix budgeting with variance analysis, prices of procedures and epidemiological data. The authors believe that only the managerial approach combining medical and economic disciplines can meet the challenges of the changing modern economic environment.

Data collection challenges in community settings: Insights from two field studies of patients with chronic disease

PubMed Central

Holden, Richard J.; McDougald Scott, Amanda M.; Hoonakker, Peter L.T.; Hundt, Ann S.; Carayon, Pascale

2014-01-01

Purpose Collecting information about health and disease directly from patients can be fruitfully accomplished using contextual approaches, ones that combine more and less structured methods in home and community settings. This paper's purpose is to describe and illustrate a framework of the challenges of contextual data collection. Methods A framework is presented based on prior work in community-based participatory research and organizational science, comprised of ten types of challenges across four broader categories. Illustrations of challenges and suggestions for addressing them are drawn from two mixed-method, contextual studies of patients with chronic disease in two regions of the US. Results The first major category of challenges was concerned with the researcher-participant partnership, for example, the initial lack of mutual trust and understanding between researchers, patients, and family members. The second category concerned patient characteristics such as cognitive limitations and a busy personal schedule that created barriers to successful data collection. The third concerned research logistics and procedures such as recruitment, travel distances, and compensation. The fourth concerned scientific quality and interpretation, including issues of validity, reliability, and combining data from multiple sources. The two illustrative studies faced both common and diverse research challenges and used many different strategies to address them. Conclusion Collecting less structured data from patients and others in the community is potentially very productive but requires the anticipation, avoidance, or negotiation of various challenges. Future work is necessary to better understand these challenges across different methods and settings, as well as to test and identify strategies to address them. PMID:25154464

Promoting Success in the Physical Sciences: The University of Wisconsin's Physics Learning Program

NASA Astrophysics Data System (ADS)

Nossal, S. M.; Jacob, A. T.

2002-05-01

The Physics Learning Program at the University of Wisconsin-Madison provides small group, academic and mentoring support for students enrolled in algebra-based introductory physics courses. Those students accepted into our program are potentially at-risk academically in their physics course or for feeling isolated at the University. They include, among others, students who have not taken high school physics, returning adults, minority students, students with disabilities, and students with English as a second language. A core component of the program is the peer-lead teaching and mentoring groups that match upper level undergraduate physics majors with students potentially at-risk in introductory physics. The tutors receive ongoing training and supervision throughout the year. The program has expanded over the years to include staff tutors, the majority of whom are scientists who seek additional teaching experience. The Physics Peer Mentor Tutor Program is run in collaboration with a similar chemistry program at the University of Wisconsin's Chemistry Learning Center. We will describe our Physics Learning Programs and discuss some of the challenges, successes, and strategies used to work with our tutors and students.

[Computational medical imaging (radiomics) and potential for immuno-oncology].

PubMed

Sun, R; Limkin, E J; Dercle, L; Reuzé, S; Zacharaki, E I; Chargari, C; Schernberg, A; Dirand, A S; Alexis, A; Paragios, N; Deutsch, É; Ferté, C; Robert, C

2017-10-01

The arrival of immunotherapy has profoundly changed the management of multiple cancers, obtaining unexpected tumour responses. However, until now, the majority of patients do not respond to these new treatments. The identification of biomarkers to determine precociously responding patients is a major challenge. Computational medical imaging (also known as radiomics) is a promising and rapidly growing discipline. This new approach consists in the analysis of high-dimensional data extracted from medical imaging, to further describe tumour phenotypes. This approach has the advantages of being non-invasive, capable of evaluating the tumour and its microenvironment in their entirety, thus characterising spatial heterogeneity, and being easily repeatable over time. The end goal of radiomics is to determine imaging biomarkers as decision support tools for clinical practice and to facilitate better understanding of cancer biology, allowing the assessment of the changes throughout the evolution of the disease and the therapeutic sequence. This review will develop the process of computational imaging analysis and present its potential in immuno-oncology. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Myeloid neoplasms with germline DDX41 mutation.

PubMed

Cheah, Jesse J C; Hahn, Christopher N; Hiwase, Devendra K; Scott, Hamish S; Brown, Anna L

2017-08-01

Recently, DDX41 mutations have been identified both as germline and acquired somatic mutations in families with multiple cases of late-onset myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. The majority of germline mutations are frameshift mutations suggesting loss of function with DDX41 acting as a tumor suppressor, and there is a common somatic missense mutation found in a majority of germline mutated tumors. Clinically, DDX41 mutations lead to development of high-risk MDS at an age similar to that observed in sporadic cohorts, presenting a unique challenge to hematologists in recognizing the familial context. Functionally, DDX41 has been shown to contribute to multiple pathways and processes including mRNA splicing, innate immunity and rRNA processing. Mutations in DDX41 result in aberrations to each of these in ways that could potentially impact on tumorigenesis-initiation, maintenance or progression. This review discusses the various molecular, clinical and biological aspects of myeloid malignancy predisposition due to DDX41 mutation and highlights how each of these suggest potential therapeutic opportunities through the use of pathway-specific inhibitors.

Biomimetics in Tribology

NASA Astrophysics Data System (ADS)

Gebeshuber, I. C.; Majlis, B. Y.; Stachelberger, H.

Science currently goes through a major change. Biology is evolving as new Leitwissenschaft, with more and more causation and natural laws being uncovered. The term `technoscience' denotes the field where science and technology are inseparably interconnected, the trend goes from papers to patents, and the scientific `search for truth' is increasingly replaced by search for applications with a potential economic value. Biomimetics, i.e. knowledge transfer from biology to technology, is a field that has the potential to drive major technical advances. The biomimetic approach might change the research landscape and the engineering culture dramatically, by the blending of disciplines. It might substantially support successful mastering of current tribological challenges: friction, adhesion, lubrication and wear in devices and systems from the meter to the nanometer scale. A highly successful method in biomimectics, the biomimicry innovation method, is applied in this chapter to identify nature's best practices regarding two key issues in tribology: maintenance of the physical integrity of a system, and permanent as well as temporary attachment. The best practices identified comprise highly diverse organisms and processes and are presented in a number of tables with detailed references.

In Search of a Cure for Sepsis: Taming the Monster in Critical Care Medicine.

PubMed

Okeke, Emeka B; Uzonna, Jude E

2016-01-01

In spite of over half a century of research, sepsis still constitutes a major problem in health care delivery. Although advances in research have significantly increased our knowledge of the pathogenesis of sepsis and resulted in better prognosis and improved survival outcome, sepsis still remains a major challenge in modern medicine with an increase in occurrence predicted and a huge socioeconomic burden. It is generally accepted that sepsis is due to an initial hyperinflammatory response. However, numerous efforts aimed at targeting the proinflammatory cytokine network have been largely unsuccessful and the search for novel potential therapeutic targets continues. Recent studies provide compelling evidence that dysregulated anti-inflammatory responses may also contribute to sepsis mortality. Our previous studies on the role of regulatory T cells and phosphoinositide 3-kinases in sepsis highlight immunological approaches that could be explored for sepsis therapy. In this article, we review the current and emerging concepts in sepsis, highlight novel potential therapeutic targets and immunological approaches for sepsis treatment and propose a biphasic treatment approach for management of the condition. © 2016 S. Karger AG, Basel.

Undergraduate Neuroscience Majors: A Missed Opportunity for Psychiatry Workforce Development.

PubMed

Goldenberg, Matthew N; Krystal, John H

2017-04-01

This study sought to determine whether and to what extent medical students with an undergraduate college major in neuroscience, relative to other college majors, pursue psychiatry relative to other brain-based specialties (neurology and neurosurgery) and internal medicine. The authors analyzed data from AAMC matriculation and graduation surveys for all students who graduated from US medical schools in 2013 and 2014 (n = 29,714). Students who majored in neuroscience, psychology, and biology were compared to all other students in terms of their specialty choice at both time points. For each major, the authors determined rates of specialty choice of psychiatry, neurology, neurosurgery, and, for comparison, internal medicine. This study employed Chi-square statistic to compare odds of various specialty choices among different majors. Among medical students with an undergraduate neuroscience major (3.5% of all medical students), only 2.3% preferred psychiatry at matriculation, compared to 21.5% who chose neurology, 13.1% neurosurgery, and 11% internal medicine. By graduation, psychiatry specialty choice increased to 5.1% among neuroscience majors while choice of neurology and neurosurgery declined. Psychology majors (OR = 3.16, 95% CI 2.60-4.47) but not neuroscience majors (OR 1.28, 0.92-1.77) were more likely than their peers to choose psychiatry. Psychiatry struggles to attract neuroscience majors to the specialty. This missed opportunity is an obstacle to developing the neuroscience literacy of the workforce and jeopardizes the neuroscientific future of our field. Several potential strategies to address the recruitment challenges exist.

Bright Side of Lignin Depolymerization: Toward New Platform Chemicals

PubMed Central

2018-01-01

Lignin, a major component of lignocellulose, is the largest source of aromatic building blocks on the planet and harbors great potential to serve as starting material for the production of biobased products. Despite the initial challenges associated with the robust and irregular structure of lignin, the valorization of this intriguing aromatic biopolymer has come a long way: recently, many creative strategies emerged that deliver defined products via catalytic or biocatalytic depolymerization in good yields. The purpose of this review is to provide insight into these novel approaches and the potential application of such emerging new structures for the synthesis of biobased polymers or pharmacologically active molecules. Existing strategies for functionalization or defunctionalization of lignin-based compounds are also summarized. Following the whole value chain from raw lignocellulose through depolymerization to application whenever possible, specific lignin-based compounds emerge that could be in the future considered as potential lignin-derived platform chemicals. PMID:29337543

Geodesy and metrology with a transportable optical clock

NASA Astrophysics Data System (ADS)

Grotti, Jacopo; Koller, Silvio; Vogt, Stefan; Häfner, Sebastian; Sterr, Uwe; Lisdat, Christian; Denker, Heiner; Voigt, Christian; Timmen, Ludger; Rolland, Antoine; Baynes, Fred N.; Margolis, Helen S.; Zampaolo, Michel; Thoumany, Pierre; Pizzocaro, Marco; Rauf, Benjamin; Bregolin, Filippo; Tampellini, Anna; Barbieri, Piero; Zucco, Massimo; Costanzo, Giovanni A.; Clivati, Cecilia; Levi, Filippo; Calonico, Davide

2018-05-01

Optical atomic clocks, due to their unprecedented stability1-3 and uncertainty3-6, are already being used to test physical theories7,8 and herald a revision of the International System of Units9,10. However, to unlock their potential for cross-disciplinary applications such as relativistic geodesy11, a major challenge remains: their transformation from highly specialized instruments restricted to national metrology laboratories into flexible devices deployable in different locations12-14. Here, we report the first field measurement campaign with a transportable 87Sr optical lattice clock12. We use it to determine the gravity potential difference between the middle of a mountain and a location 90 km away, exploiting both local and remote clock comparisons to eliminate potential clock errors. A local comparison with a 171Yb lattice clock15 also serves as an important check on the international consistency of independently developed optical clocks. This campaign demonstrates the exciting prospects for transportable optical clocks.

Accuracy of professional sports drafts in predicting career potential.

PubMed

Koz, D; Fraser-Thomas, J; Baker, J

2012-08-01

The forecasting of talented players is a crucial aspect of building a successful sports franchise and professional sports invest significant resources in making player choices in sport drafts. The current study examined the relationship between career performance (i.e. games played) and draft round for the National Football League, National Hockey League, National Basketball League, and Major League Baseball for players drafted from 1980 to 1989 (n = 4874) against the assumption of a linear relationship between performance and draft round (i.e. that players with the most potential will be selected before players of lower potential). A two-step analysis revealed significant differences in games played across draft rounds (step 1) and a significant negative relationship between draft round and games played (step 2); however, the amount of variance accounted for was relatively low (less than 17%). Results highlight the challenges of accurately evaluating amateur talent. © 2011 John Wiley & Sons A/S.

The Psychosis High-Risk State

PubMed Central

Fusar-Poli, Paolo; Borgwardt, Stefan; Bechdolf, Andreas; Addington, Jean; Riecher-Rössler, Anita; Schultze-Lutter, Frauke; Keshavan, Matcheri; Wood, Stephen; Ruhrmann, Stephan; Seidman, Larry J.; Valmaggia, Lucia; Cannon, Tyrone; Velthorst, Eva; De Haan, Lieuwe; Cornblatt, Barbara; Bonoldi, Ilaria; Birchwood, Max; McGlashan, Thomas; Carpenter, William; McGorry, Patrick; Klosterkötter, Joachim; McGuire, Philip; Yung, Alison

2014-01-01

Context During the past 2 decades, a major transition in the clinical characterization of psychotic disorders has occurred. The construct of a clinical high-risk (HR) state for psychosis has evolved to capture the prepsychotic phase, describing people presenting with potentially prodromal symptoms. The importance of this HR state has been increasingly recognized to such an extent that a new syndrome is being considered as a diagnostic category in the DSM-5. Objective To reframe the HR state in a comprehensive state-of-the-art review on the progress that has been made while also recognizing the challenges that remain. Data Sources Available HR research of the past 20 years from PubMed, books, meetings, abstracts, and international conferences. Study Selection and Data Extraction Critical review of HR studies addressing historical development, inclusion criteria, epidemiologic research, transition criteria, outcomes, clinical and functional characteristics, neurocognition, neuroimaging, predictors of psychosis development, treatment trials, socioeconomic aspects, nosography, and future challenges in the field. Data Synthesis Relevant articles retrieved in the literature search were discussed by a large group of leading worldwide experts in the field. The core results are presented after consensus and are summarized in illustrative tables and figures. Conclusions The relatively new field of HR research in psychosis is exciting. It has the potential to shed light on the development of major psychotic disorders and to alter their course. It also provides a rationale for service provision to those in need of help who could not previously access it and the possibility of changing trajectories for those with vulnerability to psychotic illnesses. PMID:23165428

Malnutrition in South Asia-A Critical Reappraisal.

PubMed

Akhtar, Saeed

2016-10-25

Malnutrition continues to be a major public health challenge especially in South Asian developing countries. The aim of the present review is to spotlight the magnitude of the prevalence of malnutrition and its dynamics in South Asian region and to suggest potential approaches for the prevention and control of this issue of public health significance. An extensive review of literature, covering malnutrition and its determinants, health and economic consequences and pragmatic preventive strategies was performed on computer based bibliographic databases (PubMed, Google Scholar, Scopus, Medline and Sciencedirect.com ) to retrieve abstracts and full texts for India, Pakistan, Bangladesh, Sri Lanka and Nepal. All relevant titles and abstracts were examined and evaluated for malnutrition and its prevalence in South Asia. The results revealed malnutrition to be a major public health problem and a potential cause of high disease burden and mortality in South Asia. Compelling evidence suggests malnutrition to be the leading cause of stunting, wasting and underweight with drastic economic consequences among vulnerable populations. Reduced cognitive performance and low productivity have also been associated with micronutrients malnutrition. Suboptimal breastfeeding, inadequate food supply, micronutrient deficiencies, low household income, poor health care system, increased healthcare costs, illiteracy, unhygienic and substandard living, inappropriate child's care and the caregiver, food insecurity and on top of that vicious cycle of poverty, have been recognized as principal indicators for growing malnutrition prevalence in South Asia. Global organizations, local governments, program managers, NGOs, academia, industry in particular and the society at large need to take up the challenge to completely confiscate malnutrition from the region for economic prosperity and a healthier future.

Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems

NASA Astrophysics Data System (ADS)

Mullen, Douglas Gurnett

Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution. Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation. With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules can be attached and has the potential to dramatically improve platform efficacy. An additional investigation of reproducibility challenges for current dendrimer-based platform designs is also described. The mass transport quality during the partial acetylation reaction of the dendrimer was found to have a major impact on subsequent dendrimer-ligand distributions that cannot be detected by standard analytical techniques. Consequently, this reaction should be eliminated from the platform design. Finally, optimized protocols for purification and characterization of PAMAM dendrimer were detailed.

The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders.

PubMed

Chang, H; Hoshina, N; Zhang, C; Ma, Y; Cao, H; Wang, Y; Wu, D-D; Bergen, S E; Landén, M; Hultman, C M; Preisig, M; Kutalik, Z; Castelao, E; Grigoroiu-Serbanescu, M; Forstner, A J; Strohmaier, J; Hecker, J; Schulze, T G; Müller-Myhsok, B; Reif, A; Mitchell, P B; Martin, N G; Schofield, P R; Cichon, S; Nöthen, M M; Walter, H; Erk, S; Heinz, A; Amin, N; van Duijn, C M; Meyer-Lindenberg, A; Tost, H; Xiao, X; Yamamoto, T; Rietschel, M; Li, M

2018-02-01

Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.

Challenges facing effective implementation of co-trimoxazole prophylaxis in children born to HIV-infected mothers in the public health facilities.

PubMed

Kamuhabwa, Appolinary Ar; Manyanga, Vicky

2015-01-01

If children born to HIV-infected mothers are not identified early, approximately 30% of them will die within the first year of life due to opportunistic infections. In order to prevent morbidity and mortality due to opportunistic infections in children, the World Health Organization recommends the use of prophylaxis using co-trimoxazole. However, the challenges affecting effective implementation of this policy in Tanzania have not been documented. In this study, we assessed the challenges facing the provision of co-trimoxazole prophylaxis among children born to HIV-infected mothers in the public hospitals of Dar es Salaam, Tanzania. Four hundred and ninety-eight infants' PMTCT (Prevention of Mother-to-Child Transmission of HIV) register books for the past 2 years were reviewed to obtain information regarding the provision of co-trimoxazole prophylaxis. One hundred and twenty-six health care workers were interviewed to identify success stories and challenges in the provision of co-trimoxazole prophylaxis in children. In addition, 321 parents and guardians of children born to HIV-infected mothers were interviewed in the health facilities. Approximately 80% of children were initiated with co-trimoxazole prophylaxis within 2 months after birth. Two hundred and ninety-one (58.4%) children started using co-trimoxazole within 4 weeks after birth. Majority (n=458, 91.8%) of the children were prescribed 120 mg of co-trimoxazole per day, whereas 39 (7.8%) received 240 mg per day. Only a small proportion (n=1, 0.2%) of children received 480 mg/day. Dose determination was based on the child's age rather than body weight. Parents and guardians reported that 42 (13.1%) children had missed one or more doses of co-trimoxazole during the course of prophylaxis. The majority of health care workers (89.7%) reported that co-trimoxazole is very effective for the prevention of opportunistic infections among children, but frequent shortage of co-trimoxazole in the health facilities was the main challenge. Most children who were initiated with co-trimoxazole prophylaxis did not experience significant opportunistic infections, and the drug was well tolerated. The major barrier for co-trimoxazole prophylaxis was due to frequent out-of-stocks of pediatric co-trimoxazole formulations in the health facilities. Dose determination was based on the age rather than the weight of children, thus creating potential for under- or over-dosing of children.

Common Challenges Faced by Women of Color in Physics, and Actions Faculty Can Take to Minimize Those Challenges

NASA Astrophysics Data System (ADS)

Johnson, Angela; Ong, Maria; Ko, Lily T.; Smith, Janet; Hodari, Apriel

2017-09-01

Women of color are deeply underrepresented in physics. Between 2002 and 2012, only 1% of graduating physics majors were Black women and another 1% were Latinas; only 61 American Indian women total completed degrees in physics in those years (out of 48,000 physics majors). This isolation can lead to additional obstacles that women of color majoring in physics must face above and beyond the challenging material. In this article we draw on qualitative findings to describe common obstacles women of color face. However, departments can take deliberate steps so that underrepresentation need not turn into loneliness and isolation. We describe the characteristics of a department where women of color report that they are thriving. We end with concrete steps physics faculty can take to support women physics majors of color.

What Are the Lived Challenges Experienced by Black Females in a STEM Doctoral Program at a Majority White Institution?

NASA Astrophysics Data System (ADS)

Cleare, Sharlane S.

The purpose of this study is to explore the challenges experienced by Black female STEM doctoral students at a Majority White Institution. This study examined how, and to what extent did the Majority White Institution's STEM environment influenced such challenges. The qualitative phenomenological approach to this investigation utilized the lenses of Black Feminist Thought and Critical Race Feminism Theoretical Frameworks as interconnected lenses by which to conceptualize this phenomenon. This study answered the following question: What are the lived challenges experienced by Black female in a STEM doctoral program at a Majority White Institution? Purposeful and snowball sampling were employed to recruit participants for this investigation. Both sampling methods were selected because of their wide use in qualitative investigations, as well as their proven ability to precisely source quality participants (Biernacki, & Waldorf,1981; Palinkas, Horwitz, Green, Wisdom, Duan, & Hoagwood, (2015). Observations, in-depth semi-structured interviews, and focus groups were conducted with eleven (11) Black females STEM doctoral students currently studying at a large Majority White Institution in the Midwest. The findings from this study suggest that this is a phenomenon worthy of considerable attention. Research in the area of Black females in STEM doctoral programs at Majority White Institutions can be further expanded and updated. Therefore, this study will contribute and supplement existing literature on Black females in STEM doctoral programs at Majority White Institutions. Most importantly, the results obtained from this study can assist Majority White Institutions in the development and enhancement of programs and policies specifically geared towards addressing the needs of this underrepresented minority population segment.

Crystalline, Highly Oriented MOF Thin Film: the Fabrication and Application.

PubMed

Fu, Zhihua; Xu, Gang

2017-05-01

The thin film of metal-organic frameworks (MOFs) is a rapidly developing research area which has tremendous potential applications in many fields. One of the major challenges in this area is to fabricate MOF thin film with good crystallinity, high orientation and well-controlled thickness. In order to address this challenge, different appealing approaches have been studied intensively. Among various oriented MOF films, many efforts have also been devoted to developing novel properties and broad applications, such as in gas separator, thermoelectric, storage medium and photovoltaics. As a result, there has been a large demand for fundamental studies that can provide guidance and experimental data for further applications. In this account, we intend to present an overview of current synthetic methods for fabricating oriented crystalline MOF thin film and bring some updated applications. We give our perspective on the background, preparation and applications that led to the developments in this area and discuss the opportunities and challenges of using crystalline, highly oriented MOF thin film. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Group Health Coaching: Strengths, Challenges, and Next Steps

PubMed Central

Wolever, Ruth Q.; Manning, Linda; Elam, Roy; Moore, Margaret; Frates, Elizabeth Pegg; Duskey, Heidi; Anderson, Chelsea; Curtis, Rebecca L.; Masemer, Susan; Lawson, Karen

2013-01-01

There is great need for cost effective approaches to increase patient engagement and improve health and well-being. Health and wellness coaching has recently demonstrated great promise, but the majority of studies to date have focused on individual coaching (ie, one coach with one client). Newer initiatives are bringing a group coaching model from corporate leadership development and educational settings into the healthcare arena. A group approach potentially increases cost-effective access to a larger number of clients and brings the possible additional benefit of group support. This article highlights some of the group coaching approaches currently being conducted across the United States. The group coaching interventions included in this overview are offered by a variety of academic and private sector institutions, use both telephonic and in-person coaching, and are facilitated by professionally trained health and wellness coaches as well as trained peer coaches. Strengths and challenges experienced in these efforts are summarized, as are recommendations to address those challenges. A working definition of “Group Health and Wellness Coaching” is proposed, and important next steps for research and for the training of group coaches are presented. PMID:24416678

Social and ecological challenges of market-oriented shrimp farming in Vietnam.

PubMed

Lan, Ngo Thi Phuong

2013-01-01

Vietnam is one of the largest shrimp exporters in the world. Since 2010, Vietnam has earned about two billion dollars annually through shrimp exports. As a fertile area of greatest potential for agricultural production in Vietnam, the Mekong Delta has been a major contributor to the country's achievements, especially in the agricultural sector. During recent decades, trade liberation along with various policies in support of aquaculture has accelerated the development of shrimp production in the Delta. Based on an ethnographic study of shrimp farming in the Mekong Delta of Vietnam, I assert that along with great rewards arising from the expansion of shrimp farming areas, productivity, and export value, the shrimp industry has brought various environmental, economic and social challenges. Consequently, shrimp farming is a risky business and local inhabitants have relied on various strategies to cope with these challenges. Risk mitigation in shrimp production and labor migration are the two important strategies of local inhabitants for securing their livelihoods. Water pollution and poor quality post-larvae shrimp are direct consequences of market-oriented production.

The 2017 Plasma Roadmap: Low temperature plasma science and technology

NASA Astrophysics Data System (ADS)

Adamovich, I.; Baalrud, S. D.; Bogaerts, A.; Bruggeman, P. J.; Cappelli, M.; Colombo, V.; Czarnetzki, U.; Ebert, U.; Eden, J. G.; Favia, P.; Graves, D. B.; Hamaguchi, S.; Hieftje, G.; Hori, M.; Kaganovich, I. D.; Kortshagen, U.; Kushner, M. J.; Mason, N. J.; Mazouffre, S.; Mededovic Thagard, S.; Metelmann, H.-R.; Mizuno, A.; Moreau, E.; Murphy, A. B.; Niemira, B. A.; Oehrlein, G. S.; Petrovic, Z. Lj; Pitchford, L. C.; Pu, Y.-K.; Rauf, S.; Sakai, O.; Samukawa, S.; Starikovskaia, S.; Tennyson, J.; Terashima, K.; Turner, M. M.; van de Sanden, M. C. M.; Vardelle, A.

2017-08-01

Journal of Physics D: Applied Physics published the first Plasma Roadmap in 2012 consisting of the individual perspectives of 16 leading experts in the various sub-fields of low temperature plasma science and technology. The 2017 Plasma Roadmap is the first update of a planned series of periodic updates of the Plasma Roadmap. The continuously growing interdisciplinary nature of the low temperature plasma field and its equally broad range of applications are making it increasingly difficult to identify major challenges that encompass all of the many sub-fields and applications. This intellectual diversity is ultimately a strength of the field. The current state of the art for the 19 sub-fields addressed in this roadmap demonstrates the enviable track record of the low temperature plasma field in the development of plasmas as an enabling technology for a vast range of technologies that underpin our modern society. At the same time, the many important scientific and technological challenges shared in this roadmap show that the path forward is not only scientifically rich but has the potential to make wide and far reaching contributions to many societal challenges.

Successful use of tablet personal computers and wireless technologies for the 2011 Nepal Demographic and Health Survey.

PubMed

Paudel, Deepak; Ahmed, Marie; Pradhan, Anjushree; Lal Dangol, Rajendra

2013-08-01

Computer-Assisted Personal Interviewing (CAPI), coupled with the use of mobile and wireless technology, is growing as a data collection methodology. Nepal, a geographically diverse and resource-scarce country, implemented the 2011 Nepal Demographic and Health Survey, a nationwide survey of major health indicators, using tablet personal computers (tablet PCs) and wireless technology for the first time in the country. This paper synthesizes responses on the benefits and challenges of using new technology in such a challenging environment from the 89 interviewers who administered the survey. Overall, feedback from the interviewers indicate that the use of tablet PCs and wireless technology to administer the survey demonstrated potential to improve data quality and reduce data collection time-benefits that outweigh manageable challenges, such as storage and transport of the tablet PCs during fieldwork, limited options for confidential interview space due to screen readability issues under direct sunlight, and inconsistent electricity supply at times. The introduction of this technology holds great promise for improving data availability and quality, even in a context with limited infrastructure and extremely difficult terrain.

Group health coaching: strengths, challenges, and next steps.

PubMed

Armstrong, Colin; Wolever, Ruth Q; Manning, Linda; Elam, Roy; Moore, Margaret; Frates, Elizabeth Pegg; Duskey, Heidi; Anderson, Chelsea; Curtis, Rebecca L; Masemer, Susan; Lawson, Karen

2013-05-01

There is great need for cost effective approaches to increase patient engagement and improve health and well-being. Health and wellness coaching has recently demonstrated great promise, but the majority of studies to date have focused on individual coaching (ie, one coach with one client). Newer initiatives are bringing a group coaching model from corporate leadership development and educational settings into the healthcare arena. A group approach potentially increases cost-effective access to a larger number of clients and brings the possible additional benefit of group support. This article highlights some of the group coaching approaches currently being conducted across the United States. The group coaching interventions included in this overview are offered by a variety of academic and private sector institutions, use both telephonic and in-person coaching, and are facilitated by professionally trained health and wellness coaches as well as trained peer coaches. Strengths and challenges experienced in these efforts are summarized, as are recommendations to address those challenges. A working definition of "Group Health and Wellness Coaching" is proposed, and important next steps for research and for the training of group coaches are presented.

Photodynamic therapy for treatment of solid tumors – potential and technical challenges

PubMed Central

Huang, Zheng; Xu, Heping; Meyers, Arlen D.; Musani, Ali I.; Wang, Luowei; Tagg, Randall; Barqawi, Al B.; Chen, Yang K.

2008-01-01

Photodynamic therapy (PDT) involves the administration of photosensitizer followed by local illumination with visible light of specific wavelength(s). In the presence of oxygen molecules, the light illumination of photosensitizer can lead to a series of photochemical reactions and consequently the generation of cytotoxic species. The quantity and location of PDT-induced cytotoxic species determine the nature and consequence of PDT. Much progress has been seen in both basic research and clinical application in recent years. Although the majority of approved PDT clinical protocols have primarily been used for the treatment of superficial lesions of both malignant and non-malignant diseases, interstitial PDT for the ablation of deep-seated solid tumors are now being investigated worldwide. The complexity of the geometry and non-homogeneity of solid tumor pose a great challenge on the implementation of minimally invasive interstitial PDT and the estimation of PDT dosimetry. This review will discuss the recent progress and technical challenges of various forms of interstitial PDT for the treatment of parenchymal and/or stromal tissues of solid tumors. PMID:18642969

Decellularized scaffold of cryopreserved rat kidney retains its recellularization potential.

PubMed

Chani, Baldeep; Puri, Veena; Sobti, Ranbir C; Jha, Vivekanand; Puri, Sanjeev

2017-01-01

The multi-cellular nature of renal tissue makes it the most challenging organ for regeneration. Therefore, till date whole organ transplantations remain the definitive treatment for the end stage renal disease (ESRD). The shortage of available organs for the transplantation has, thus, remained a major concern as well as an unsolved problem. In this regard generation of whole organ scaffold through decellularization followed by regeneration of the whole organ by recellularization is being viewed as a potential alternative for generating functional tissues. Despite its growing interest, the optimal processing to achieve functional organ still remains unsolved. The biggest challenge remains is the time line for obtaining kidney. Keeping these facts in mind, we have assessed the effects of cryostorage (3 months) on renal tissue architecture and its potential for decellularization and recellularization in comparison to the freshly isolated kidneys. The light microscopy exploiting different microscopic stains as well as immuno-histochemistry and Scanning electron microscopy (SEM) demonstrated that ECM framework is well retained following kidney cryopreservation. The strength of these structures was reinforced by calculating mechanical stress which confirmed the similarity between the freshly isolated and cryopreserved tissue. The recellularization of these bio-scaffolds, with mesenchymal stem cells quickly repopulated the decellularized structures irrespective of the kidneys status, i.e. freshly isolated or the cryopreserved. The growth pattern employing mesenchymal stem cells demonstrated their equivalent recellularization potential. Based on these observations, it may be concluded that cryopreserved kidneys can be exploited as scaffolds for future development of functional organ.

Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

PubMed

Panda, R; Ariyarathna, H; Amnuaycheewa, P; Tetteh, A; Pramod, S N; Taylor, S L; Ballmer-Weber, B K; Goodman, R E

2013-02-01

Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop. © 2012 John Wiley & Sons A/S.

Potential Air Pollutant Emissions and Permitting Classifications for Two Biorefinery Process Designs in the United States.

PubMed

Eberle, Annika; Bhatt, Arpit; Zhang, Yimin; Heath, Garvin

2017-06-06

Advanced biofuel production facilities (biorefineries), such as those envisioned by the United States (U.S.) Renewable Fuel Standard and U.S. Department of Energy's research and development programs, often lack historical air pollutant emissions data, which can pose challenges for obtaining air emission permits that are required for construction and operation. To help fill this knowledge gap, we perform a thorough regulatory analysis and use engineering process designs to assess the applicability of federal air regulations and quantify air pollutant emissions for two feasibility-level biorefinery designs. We find that without additional emission-control technologies both biorefineries would likely be required to obtain major source permits under the Clean Air Act's New Source Review program. The permitting classification (so-called "major" or "minor") has implications for the time and effort required for permitting and therefore affects the cost of capital and the fuel selling price. Consequently, we explore additional technically feasible emission-control technologies and process modifications that have the potential to reduce emissions to achieve a minor source permitting classification. Our analysis of air pollutant emissions and controls can assist biorefinery developers with the air permitting process and inform regulatory agencies about potential permitting pathways for novel biorefinery designs.

Rare Cell Capture in Microfluidic Devices

PubMed Central

Pratt, Erica D.; Huang, Chao; Hawkins, Benjamin G.; Gleghorn, Jason P.; Kirby, Brian J.

2010-01-01

This article reviews existing methods for the isolation, fractionation, or capture of rare cells in microfluidic devices. Rare cell capture devices face the challenge of maintaining the efficiency standard of traditional bulk separation methods such as flow cytometers and immunomagnetic separators while requiring very high purity of the target cell population, which is typically already at very low starting concentrations. Two major classifications of rare cell capture approaches are covered: (1) non-electrokinetic methods (e.g., immobilization via antibody or aptamer chemistry, size-based sorting, and sheath flow and streamline sorting) are discussed for applications using blood cells, cancer cells, and other mammalian cells, and (2) electrokinetic (primarily dielectrophoretic) methods using both electrode-based and insulative geometries are presented with a view towards pathogen detection, blood fractionation, and cancer cell isolation. The included methods were evaluated based on performance criteria including cell type modeled and used, number of steps/stages, cell viability, and enrichment, efficiency, and/or purity. Major areas for improvement are increasing viability and capture efficiency/purity of directly processed biological samples, as a majority of current studies only process spiked cell lines or pre-diluted/lysed samples. Despite these current challenges, multiple advances have been made in the development of devices for rare cell capture and the subsequent elucidation of new biological phenomena; this article serves to highlight this progress as well as the electrokinetic and non-electrokinetic methods that can potentially be combined to improve performance in future studies. PMID:21532971

The Near-Earth Orbital Debris Problem and the Challenges for Environment Remediation

NASA Technical Reports Server (NTRS)

Liou, Jer-Chyi

2012-01-01

The near-Earth space environment has been gradually polluted with orbital debris (OD) since the beginning of space activities 55 years ago. Although this problem has been known to the research community for decades, the public was, in general, unaware of the issue until the anti-satellite test conducted by China in 2007 and the collision between Cosmos 2251 and the operational Iridium 33 in 2009. The latter also underlined the potential of an ongoing collision cascade effect (the "Kessler Syndrome") in the low Earth orbit (LEO, the region below 2000 km altitude). Recent modeling results have indicated that mitigation measures commonly adopted by the international space community will be insufficient to stabilize the LEO debris population. To better limit the OD population increase, more aggressive actions must be considered. There are three options for OD environment remediation-removal of large/massive intact objects to address the root cause of the OD population growth problem, removal of 5-mm-to-1 cm debris to mitigate the main mission-ending threats for the majority of operational spacecraft, and prevention of major debris-generating collisions as a temporary means to slow down the OD population increase. The technology, engineering, and cost challenges to carry out any of these three options are monumental. It will require innovative ideas, game-changing technologies, and major collaborations at the international level to address the OD problem and preserve the near-Earth environment for future generations.

Replacement Behaviors for Identified Functions of Challenging Behaviors

ERIC Educational Resources Information Center

Matson, Johnny L.; Shoemaker, Mary E.; Sipes, Megan; Horovitz, Max; Worley, Julie A.; Kozlowski, Alison M.

2011-01-01

Functional assessment has become a major feature of learning-based research. A critical element of the majority of these studies includes not only methods and procedures to identify the cause of the challenging behavior, but to establish replacement treatment methods. By far the most common intervention in the 176 studies we reviewed was…

Implantable brain computer interface: challenges to neurotechnology translation.

PubMed

Konrad, Peter; Shanks, Todd

2010-06-01

This article reviews three concepts related to implantable brain computer interface (BCI) devices being designed for human use: neural signal extraction primarily for motor commands, signal insertion to restore sensation, and technological challenges that remain. A significant body of literature has occurred over the past four decades regarding motor cortex signal extraction for upper extremity movement or computer interface. However, little is discussed regarding postural or ambulation command signaling. Auditory prosthesis research continues to represent the majority of literature on BCI signal insertion. Significant hurdles continue in the technological translation of BCI implants. These include developing a stable neural interface, significantly increasing signal processing capabilities, and methods of data transfer throughout the human body. The past few years, however, have provided extraordinary human examples of BCI implant potential. Despite technological hurdles, proof-of-concept animal and human studies provide significant encouragement that BCI implants may well find their way into mainstream medical practice in the foreseeable future.

Reported experiences from occupational therapists interacting with teachers in inclusive early childhood classrooms.

PubMed

Bose, Pia; Hinojosa, Jim

2008-01-01

This grounded theory study described the perspectives of school-based occupational therapists working in inclusive early childhood classrooms emphasizing interactions with teaching staff. Six therapists were interviewed multiple times over several months. The participants viewed their interactions with teaching staff as challenging but potentially rewarding experiences. Viewing collaboration as valuable, their descriptions nonetheless generally omitted many collaborative features, with therapists often assigned the role of "expert." Data analysis revealed four major themes: (1) "It's Not Like I Don't Value Collaboration" (the benefits of collaboration); (2) "Collaboration--I Can't Do It Alone" (the challenges of interactions); (3) "My Opinion, Please Ask for It" (attachment to the expert status), and (4) "Is This Collaboration?" (interactions in practice). The results of this study suggest that current recommendations for collaboration for inclusion in school-based occupational therapy are not optimally implemented in all practice settings.

Additive Biotech-Chances, challenges, and recent applications of additive manufacturing technologies in biotechnology.

PubMed

Krujatz, Felix; Lode, Anja; Seidel, Julia; Bley, Thomas; Gelinsky, Michael; Steingroewer, Juliane

2017-10-25

The diversity and complexity of biotechnological applications are constantly increasing, with ever expanding ranges of production hosts, cultivation conditions and measurement tasks. Consequently, many analytical and cultivation systems for biotechnology and bioprocess engineering, such as microfluidic devices or bioreactors, are tailor-made to precisely satisfy the requirements of specific measurements or cultivation tasks. Additive manufacturing (AM) technologies offer the possibility of fabricating tailor-made 3D laboratory equipment directly from CAD designs with previously inaccessible levels of freedom in terms of structural complexity. This review discusses the historical background of these technologies, their most promising current implementations and the associated workflows, fabrication processes and material specifications, together with some of the major challenges associated with using AM in biotechnology/bioprocess engineering. To illustrate the great potential of AM, selected examples in microfluidic devices, 3D-bioprinting/biofabrication and bioprocess engineering are highlighted. Copyright © 2017 Elsevier B.V. All rights reserved.

Resources, challenges and way forward in rare mitochondrial diseases research

PubMed Central

Rajput, Neeraj Kumar; Singh, Vipin; Bhardwaj, Anshu

2015-01-01

Over 300 million people are affected by about 7000 rare diseases globally. There are tremendous resource limitations and challenges in driving research and drug development for rare diseases. Hence, innovative approaches are needed to identify potential solutions. This review focuses on the resources developed over the past years for analysis of genome data towards understanding disease biology especially in the context of mitochondrial diseases, given that mitochondria are central to major cellular pathways and their dysfunction leads to a broad spectrum of diseases. Platforms for collaboration of research groups, clinicians and patients and the advantages of community collaborative efforts in addressing rare diseases are also discussed. The review also describes crowdsourcing and crowdfunding efforts in rare diseases research and how the upcoming initiatives for understanding disease biology including analyses of large number of genomes are also applicable to rare diseases. PMID:26180633

Radio frequency analog electronics based on carbon nanotube transistors

PubMed Central

Kocabas, Coskun; Kim, Hoon-sik; Banks, Tony; Rogers, John A.; Pesetski, Aaron A.; Baumgardner, James E.; Krishnaswamy, S. V.; Zhang, Hong

2008-01-01

The potential to exploit single-walled carbon nanotubes (SWNTs) in advanced electronics represents a continuing, major source of interest in these materials. However, scalable integration of SWNTs into circuits is challenging because of difficulties in controlling the geometries, spatial positions, and electronic properties of individual tubes. We have implemented solutions to some of these challenges to yield radio frequency (RF) SWNT analog electronic devices, such as narrow band amplifiers operating in the VHF frequency band with power gains as high as 14 dB. As a demonstration, we fabricated nanotube transistor radios, in which SWNT devices provide all of the key functions, including resonant antennas, fixed RF amplifiers, RF mixers, and audio amplifiers. These results represent important first steps to practical implementation of SWNTs in high-speed analog circuits. Comparison studies indicate certain performance advantages over silicon and capabilities that complement those in existing compound semiconductor technologies. PMID:18227509

A multi target approach to control chemical reactions in their inhomogeneous solvent environment

NASA Astrophysics Data System (ADS)

Keefer, Daniel; Thallmair, Sebastian; Zauleck, Julius P. P.; de Vivie-Riedle, Regina

2015-12-01

Shaped laser pulses offer a powerful tool to manipulate molecular quantum systems. Their application to chemical reactions in solution is a promising concept to redesign chemical synthesis. Along this road, theoretical developments to include the solvent surrounding are necessary. An appropriate theoretical treatment is helpful to understand the underlying mechanisms. In our approach we simulate the solvent by randomly selected snapshots from molecular dynamics trajectories. We use multi target optimal control theory to optimize pulses for the various arrangements of explicit solvent molecules simultaneously. This constitutes a major challenge for the control algorithm, as the solvent configurations introduce a large inhomogeneity to the potential surfaces. We investigate how the algorithm handles the new challenges and how well the controllability of the system is preserved with increasing complexity. Additionally, we introduce a way to statistically estimate the efficiency of the optimized laser pulses in the complete thermodynamical ensemble.

Reprint of "EXOSOME LEVELS IN HUMAN BODY FLUIDS: A TUMOR MARKER BY THEMSELVES?"

PubMed

Cappello, Francesco; Logozzi, Mariantonia; Campanella, Claudia; Bavisotto, Celeste Caruso; Marcilla, Antonio; Properzi, Francesca; Fais, Stefano

2017-02-15

Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can at once provide with several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may by themselves represent a predictive/diagnostic of tumors, discriminating cancer patients from healthy subjects. The aim of this review is to highlight these latest challenging findings to provide novel and groundbreaking ideas for successful tumor early diagnosis and follow-up. Copyright © 2016 Elsevier B.V. All rights reserved.

When to Consider Risk-Reducing Mastectomy in BRCA1/BRCA2 Mutation Carriers with Advanced Stage Ovarian Cancer: a Case Study Illustrating the Genetic Counseling Challenges.

PubMed

Speight, Beverley; Tischkowitz, Marc

2017-12-01

Germline mutations in BRCA1/BRCA2 significantly increase the risk of breast and ovarian cancer in women. This case report describes a BRCA1 germline mutation identified in a woman with stage IV epithelial ovarian cancer and the provision of genetic counseling about BRCA1-associated breast cancer risk in the three years following diagnosis. The report centers on the patient's enquiry about risk-reducing breast surgery. We focus on the challenges for health professionals and patients in understanding and balancing the risks and benefits of major prophylactic surgery in the context of a potentially life-limiting cancer diagnosis. Breast cancer risk management in BRCA1/BRCA2 carriers with advanced ovarian cancer is an under-explored area of genetic counseling research. This article includes a case report, a review of the relevant literature and considers some implications for practice.

How to emerge from the conservatism in clinical research methodology?

PubMed

Kotecki, Nuria; Penel, Nicolas; Awada, Ahmad

2017-09-01

Despite recent changes in clinical research methodology, many challenges remain in drug development methodology. Advances in molecular biology and cancer treatments have changed the clinical research landscape. Thus, we moved from empirical clinical oncology to molecular and immunological therapeutic approaches. Along with this move, adapted dose-limiting toxicities definitions, endpoints, and dose escalation methods have been proposed. Moreover, the classical frontier between phase I, phase II, and phase III has become unclear in particular for immunological approaches. So, investigators are facing major challenges in drug development methodology. We propose to individualize clinical research using innovative approaches to significantly improve patient outcomes and targeting what is considered unmet need. Integrating high level of translational research and performing well designed biomarker studies with great potential for clinical practice are of utmost importance. This could be performed within new models of clinical research networks and by building a strong collaboration between academic, cooperative groups, on-site investigators, and pharma.

Diffusion of synthetic biology: a challenge to biosafety.

PubMed

Schmidt, Markus

2008-06-01

One of the main aims of synthetic biology is to make biology easier to engineer. Major efforts in synthetic biology are made to develop a toolbox to design biological systems without having to go through a massive research and technology process. With this "de-skilling" agenda, synthetic biology might finally unleash the full potential of biotechnology and spark a wave of innovation, as more and more people have the necessary skills to engineer biology. But this ultimate domestication of biology could easily lead to unprecedented safety challenges that need to be addressed: more and more people outside the traditional biotechnology community will create self-replicating machines (life) for civil and defence applications, "biohackers" will engineer new life forms at their kitchen table; and illicit substances will be produced synthetically and much cheaper. Such a scenario is a messy and dangerous one, and we need to think about appropriate safety standards now.

Mesenchymal stem cells in cardiac regeneration: a detailed progress report of the last 6 years (2010-2015).

PubMed

Singh, Aastha; Singh, Abhishek; Sen, Dwaipayan

2016-06-04

Mesenchymal stem cells have been used for cardiovascular regenerative therapy for decades. These cells have been established as one of the potential therapeutic agents, following several tests in animal models and clinical trials. In the process, various sources of mesenchymal stem cells have been identified which help in cardiac regeneration by either revitalizing the cardiac stem cells or revascularizing the arteries and veins of the heart. Although mesenchymal cell therapy has achieved considerable admiration, some challenges still remain that need to be overcome in order to establish it as a successful technique. This in-depth review is an attempt to summarize the major sources of mesenchymal stem cells involved in myocardial regeneration, the significant mechanisms involved in the process with a focus on studies (human and animal) conducted in the last 6 years and the challenges that remain to be addressed.

Identifying and Synchronizing Health Information Technology (HIT) Events from FDA Medical Device Reports.

PubMed

Kang, Hong; Wang, Frank; Zhou, Sicheng; Miao, Qi; Gong, Yang

2017-01-01

Health information technology (HIT) events, a subtype of patient safety events, pose a major threat and barrier toward a safer healthcare system. It is crucial to gain a better understanding of the nature of the errors and adverse events caused by current HIT systems. The scarcity of HIT event-exclusive databases and event reporting systems indicates the challenge of identifying the HIT events from existing resources. FDA Manufacturer and User Facility Device Experience (MAUDE) database is a potential resource for HIT events. However, the low proportion and the rapid evolvement of HIT-related events present challenges for distinguishing them from other equipment failures and hazards. We proposed a strategy to identify and synchronize HIT events from MAUDE by using a filter based on structured features and classifiers based on unstructured features. The strategy will help us develop and grow an HIT event-exclusive database, keeping pace with updates to MAUDE toward shared learning.

Rational design of high-yield and superior-quality rice.

PubMed

Zeng, Dali; Tian, Zhixi; Rao, Yuchun; Dong, Guojun; Yang, Yaolong; Huang, Lichao; Leng, Yujia; Xu, Jie; Sun, Chuan; Zhang, Guangheng; Hu, Jiang; Zhu, Li; Gao, Zhenyu; Hu, Xingming; Guo, Longbiao; Xiong, Guosheng; Wang, Yonghong; Li, Jiayang; Qian, Qian

2017-03-20

Rice (Oryza sativa L.) is a staple food for more than half of the world's population. To meet the ever-increasing demand for food, because of population growth and improved living standards, world rice production needs to double by 2030 1 . The development of new elite rice varieties with high yield and superior quality is challenging for traditional breeding approaches, and new strategies need to be developed. Here, we report the successful development of new elite varieties by pyramiding major genes that significantly contribute to grain quality and yield from three parents over five years. The new varieties exhibit higher yield potential and better grain quality than their parental varieties and the China's leading super-hybrid rice, Liang-you-pai-jiu (LYP9 or Pei-ai 64S/93-11). Our results demonstrate that rational design is a powerful strategy for meeting the challenges of future crop breeding, particularly in pyramiding multiple complex traits.

Hypertrophic scarring: the greatest unmet challenge following burn injury

PubMed Central

Finnerty, Celeste C; Jeschke, Marc G; Branski, Ludwik K; Barret, Juan P.; Dziewulski, Peter; Herndon, David N

2017-01-01

Summary Improvements in acute burn care have enabled patients to survive massive burns which would have once been fatal. Now up to 70% of patients develop hypertrophic scars following burns. The functional and psychosocial sequelae remain a major rehabilitative challenge, decreasing quality of life and delaying reintegration into society. The current approach is to optimise the healing potential of the burn wound using targeted wound care and surgery in order to minimise the development of hypertrophic scarring. This approach often fails, and modulation of established scar is continued although the optimal indication, timing, and combination of therapies have yet to be established. The need for novel treatments is paramount, and future efforts to improve outcomes and quality of life should include optimisation of wound healing to attenuate or prevent hypertrophic scarring, well-designed trials to confirm treatment efficacy, and further elucidation of molecular mechanisms to allow development of new preventative and therapeutic strategies. PMID:27707499

Contamination of water resources by pathogenic bacteria

PubMed Central

2014-01-01

Water-borne pathogen contamination in water resources and related diseases are a major water quality concern throughout the world. Increasing interest in controlling water-borne pathogens in water resources evidenced by a large number of recent publications clearly attests to the need for studies that synthesize knowledge from multiple fields covering comparative aspects of pathogen contamination, and unify them in a single place in order to present and address the problem as a whole. Providing a broader perceptive of pathogen contamination in freshwater (rivers, lakes, reservoirs, groundwater) and saline water (estuaries and coastal waters) resources, this review paper attempts to develop the first comprehensive single source of existing information on pathogen contamination in multiple types of water resources. In addition, a comprehensive discussion describes the challenges associated with using indicator organisms. Potential impacts of water resources development on pathogen contamination as well as challenges that lie ahead for addressing pathogen contamination are also discussed. PMID:25006540

Rock climbing: A local-global algorithm to compute minimum energy and minimum free energy pathways.

PubMed

Templeton, Clark; Chen, Szu-Hua; Fathizadeh, Arman; Elber, Ron

2017-10-21

The calculation of minimum energy or minimum free energy paths is an important step in the quantitative and qualitative studies of chemical and physical processes. The computations of these coordinates present a significant challenge and have attracted considerable theoretical and computational interest. Here we present a new local-global approach to study reaction coordinates, based on a gradual optimization of an action. Like other global algorithms, it provides a path between known reactants and products, but it uses a local algorithm to extend the current path in small steps. The local-global approach does not require an initial guess to the path, a major challenge for global pathway finders. Finally, it provides an exact answer (the steepest descent path) at the end of the calculations. Numerical examples are provided for the Mueller potential and for a conformational transition in a solvated ring system.

Implications of genome-wide association studies in cancer therapeutics.

PubMed

Patel, Jai N; McLeod, Howard L; Innocenti, Federico

2013-09-01

Genome wide association studies (GWAS) provide an agnostic approach to identifying potential genetic variants associated with disease susceptibility, prognosis of survival and/or predictive of drug response. Although these techniques are costly and interpretation of study results is challenging, they do allow for a more unbiased interrogation of the entire genome, resulting in the discovery of novel genes and understanding of novel biological associations. This review will focus on the implications of GWAS in cancer therapy, in particular germ-line mutations, including findings from major GWAS which have identified predictive genetic loci for clinical outcome and/or toxicity. Lessons and challenges in cancer GWAS are also discussed, including the need for functional analysis and replication, as well as future perspectives for biological and clinical utility. Given the large heterogeneity in response to cancer therapeutics, novel methods of identifying mechanisms and biology of variable drug response and ultimately treatment individualization will be indispensable. © 2013 The British Pharmacological Society.

Synthesis, functionalization, and applications of metal-organic frameworks in biomedicine.

PubMed

Chen, Wei; Wu, Chunsheng

2018-02-13

Metal-organic frameworks (MOFs), also known as coordination polymers, have attracted extensive research interest in the past few decades due to their unique physical structures and potentially vast applications. In this review, we outline the recent progress in the synthesis, functionalization and applications of MOFs in biomedicine, mainly focusing on two promising, yet challenging areas, i.e., drug delivery and biosensing applications. A major challenge is the proper functionalization of MOFs with demanding properties suitable for biomedical applications. Extensive studies on MOFs in biomedicine have led to substantial progress in the control of key properties of MOFs such as toxicity, size and shape, and biological stability. Due to their flexible composition, pore size and easy functionalization properties, MOFs can be utilized as key components for the development of various functional systems, and their applications in drug delivery and biosensing are reviewed. Future trends and perspectives in these research areas are also outlined.

The scientific challenges to forecasting the propagation of space weather through the heliosphere (Invited)

NASA Astrophysics Data System (ADS)

van der Holst, B.; Manchester, W.; Sokolov, I.; Toth, G.; Gombosi, T. I.

2013-12-01

Coronal mass ejections (CMEs) are a major source of potentially destructive space weather conditions. Understanding and forecasting these events are of utmost importance. In this presentation we discuss the progress towards a physics-based predictive capability within the Space Weather Modeling Framework (SWMF). We demonstrate our latest development in the AWSoM (Alfven Wave Solar Model) global model of the solar corona and inner heliosphere. This model accounts for the coupled thermodynamics of the electrons and protons via single fluid magnetohydrodynamics. The coronal heating and solar wind acceleration are addressed with Alfvén wave turbulence. The realistic 3D magnetic field is simulated using data from the photospheric magnetic field measurements. The AWSoM model serves as a workhorse for modeling CMEs from initial eruption to prediction at 1AU. With selected events we will demonstrate the complexity and challenges associated with CME propagation.

Education as an intergenerational process of human learning, teaching, and development.

PubMed

Cole, Michael

2010-11-01

In this article I argue that the future of psychological research on educational processes would benefit from an interdisciplinary approach that enables psychologists to locate their objects of study within the cultural, social, and historical contexts of their research. To make this argument, I begin by examining anthropological accounts of the characteristics of education in small, face-to-face, preindustrial societies. I then turn to a sample of contemporary psychoeducational research that seeks to implement major, qualitative changes in modern educational practices by transforming them to have the properties of education in those self-same face-to-face societies. Next I examine the challenges faced by these modern approaches and briefly describe a multi-institutional, multidisciplinary system of education that responds to these challenges while offering a model for educating psychology students in a multigenerational system of activities with potential widespread benefits. PsycINFO Database Record (c) 2010 APA, all rights reserved.

The challenge of pregnancy among homeless youth: reclaiming a lost opportunity.

PubMed

Smid, Marcela; Bourgois, Philippe; Auerswald, Colette L

2010-05-01

Young, homeless women often become pregnant, but little is known about how street youth experience their pregnancies. We documented 26 pregnancy outcomes among 13 homeless women (ages 18-26) and eight homeless men through interviews and participant-observation. Eight pregnancies were voluntarily terminated, three were miscarried, and fifteen were carried to term. Regardless of pregnancy outcome, street youths' narratives focused on ambivalence about parenting, traumatic childhood experiences, and current challenges. Despite significant obstacles, almost all were convinced of their personal capacity to change their lives. While most wanted to be parents, the majority lost custody of their newborns and consequently associated contact with medical and social services with punitive outcomes. Most of the youth who chose to terminate successfully sought safe medical care. We offer recommendations for changing the approach of services to take full advantage of pregnancy as a potential catalyst event for change in this highly vulnerable and underserved population.

The Challenge of Pregnancy among Homeless Youth: Reclaiming a Lost Opportunity

PubMed Central

Smid, Marcela; Bourgois, Philippe; Auerswald, Colette L.

2011-01-01

Young, homeless women often become pregnant, but little is known about how street youth experience their pregnancies. We documented 26 pregnancy outcomes among 13 homeless women (ages 18–26) and eight homeless men through interviews and participant-observation. Eight pregnancies were voluntarily terminated, three were miscarried, and fifteen were carried to term. Regardless of pregnancy outcome, street youths’ narratives focused on ambivalence about parenting, traumatic childhood experiences, and current challenges. Despite significant obstacles, almost all were convinced of their personal capacity to change their lives. While most wanted to be parents, the majority lost custody of their newborns and consequently associated contact with medical and social services with punitive outcomes. Most of the youth who chose to terminate successfully sought safe medical care. We offer recommendations for changing the approach of services to take full advantage of pregnancy as a potential catalyst event for change in this highly vulnerable and underserved population. PMID:20453382

A Geology Sampling System for Small Bodies

NASA Technical Reports Server (NTRS)

Hood, A. D.; Naids, A. J.; Graff, T.; Abell, P.

2015-01-01

Human exploration of Small Bodies is being investigated as a precursor to a Mars surface mission. Asteroids, comets, dwarf planets, and the moons of Mars all fall into this Small Bodies category and some are being discussed as potential mission tar-gets. Obtaining geological samples for return to Earth will be a major objective for any mission to a Small Body. Currently the knowledge base for geology sampling in microgravity is in its infancy. Furthermore, humans interacting with non-engineered surfaces in a microgravity environment poses unique challenges. In preparation for such missions, a team at the National Aeronautics and Space Administration (NASA) John-son Space Center (JSC) has been working to gain experience on how to safely obtain numerous sample types in such an environment. This abstract briefly summarizes the type of samples the science community is interested in, discusses an integrated geology sampling solution, and highlights some of the unique challenges associated with this type of exploration.

Alloy-Based Anode Materials toward Advanced Sodium-Ion Batteries.

PubMed

Lao, Mengmeng; Zhang, Yu; Luo, Wenbin; Yan, Qingyu; Sun, Wenping; Dou, Shi Xue

2017-12-01

Sodium-ion batteries (SIBs) are considered as promising alternatives to lithium-ion batteries owing to the abundant sodium resources. However, the limited energy density, moderate cycling life, and immature manufacture technology of SIBs are the major challenges hindering their practical application. Recently, numerous efforts are devoted to developing novel electrode materials with high specific capacities and long durability. In comparison with carbonaceous materials (e.g., hard carbon), partial Group IVA and VA elements, such as Sn, Sb, and P, possess high theoretical specific capacities for sodium storage based on the alloying reaction mechanism, demonstrating great potential for high-energy SIBs. In this review, the recent research progress of alloy-type anodes and their compounds for sodium storage is summarized. Specific efforts to enhance the electrochemical performance of the alloy-based anode materials are discussed, and the challenges and perspectives regarding these anode materials are proposed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Germanium Based Field-Effect Transistors: Challenges and Opportunities

PubMed Central

Goley, Patrick S.; Hudait, Mantu K.

2014-01-01

The performance of strained silicon (Si) as the channel material for today’s metal-oxide-semiconductor field-effect transistors may be reaching a plateau. New channel materials with high carrier mobility are being investigated as alternatives and have the potential to unlock an era of ultra-low-power and high-speed microelectronic devices. Chief among these new materials is germanium (Ge). This work reviews the two major remaining challenges that Ge based devices must overcome if they are to replace Si as the channel material, namely, heterogeneous integration of Ge on Si substrates, and developing a suitable gate stack. Next, Ge is compared to compound III-V materials in terms of p-channel device performance to review how it became the first choice for PMOS devices. Different Ge device architectures, including surface channel and quantum well configurations, are reviewed. Finally, state-of-the-art Ge device results and future prospects are also discussed. PMID:28788569

[3D bioprinting of cartilage: challenges concerning the reconstruction of a burned ear].

PubMed

Visscher, Dafydd O; Bos, Ernst J; van Zuijlen, Paul P M

2015-01-01

Reconstruction of a severely maimed ear is a major challenge. The ear is highly flexible yet tough, and has a very complex three-dimensional shape. Reconstruction of a patient's burned ear is even more complex due to surrounding tissue damage. Not only does this hamper reconstruction options, it also increases the likelihood of issues when using synthetic implant materials. In such cases, rib cartilage is the preferred option, but this tissue has practical limitations too. For these reasons, tissue engineering and 3D bioprinting may have the potential to create personalized cartilage implants for burns patients. However, 3D bioprinting is a tool to facilitate the reconstruction, and not by itself the Holy Grail. The clinical application of this technique is still at a very early stage. Nevertheless, we expect that 3D bioprinting can be utilised for facial reconstruction following burns come 2020.

Collaborative family health care, civil rights, and social determinants of health.

PubMed

Mauksch, Larry B; Fogarty, Colleen T

2017-03-01

Social and economic disadvantage and civil rights infringement, worsens overall health (Adler, Glymour, & Fielding, 2016; McGowan, Lee, Meneses, Perkins, & Youdelman, 2016; Teitelbaum, 2005). While addressing these challenges is not new, there is reason to believe that the administration of Donald Trump and a republican majority in congress will exacerbate these challenges and their effects. How can collaborative family health care (CFHC) practitioners and our field help? The editors pondered this question and also asked a selection of leaders in the field. The editors will first share their ideas about the potential of CFHC to make a difference in daily interactions with patients. Next, they will identify key areas of risk and vulnerability. Finally, using the contributions of respected colleagues, they will propose a partial agenda for CFHC clinicians and the field. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The political solidarity model of social change: dynamics of self-categorization in intergroup power relations.

PubMed

Subasic, Emina; Reynolds, Katherine J; Turner, John C

2008-11-01

Social and political change involves a challenge to the status quo in intergroup power relations. Traditionally, the social psychology of social change has focused on disadvantaged minority groups collectively challenging the decisions, actions, and policies of those in positions of established authority. In contrast, this article presents a political solidarity model of social change that explores the process by which members of the majority challenge the authority in solidarity with the minority. It is argued that political solidarity as a social change process involves a contest between the authority and the minority over the meaning of a shared (higher order) identity with the majority. When identity ceases to be shared with the authority and becomes shared with the minority, majority challenge to authority in solidarity with the minority becomes possible. The model's contributions to existing social psychological approaches to social change are also discussed.

Baked Egg and Milk Exposure as Immunotherapy in Food Allergy.

PubMed

Leonard, Stephanie A

2016-04-01

Baked milk and egg have the potential to act as a form of oral immunotherapy (OIT). Clinical studies have shown that a majority of milk- and egg-allergic children can tolerate these allergens modified in baked form, and immunologic changes reported in subjects ingesting baked milk and egg mirror those seen in food allergy OIT trials. In addition, several studies have indicated that resolution of milk and egg allergies occur sooner in populations regularly ingesting baked milk and egg. Oral food challenges remain the best method for determining tolerability of baked milk and egg since baseline characteristics and diagnostic testing have not been reliable predictors. In this review, we explore the tolerability of baked milk and egg and their potential as OIT treatment for milk and egg allergy.

Search for a Neutron Electric Dipole Moment

PubMed Central

Golub, R.; Huffman, P. R.

2005-01-01

The possible existence of a nonzero electric dipole moment (EDM) of the neutron is of great fundamental interest in itself and directly impacts our understanding of the nature of electro-weak and strong interactions. The experimental search for this moment has the potential to reveal new sources of T and CP violation and to challenge calculations that propose extensions to the Standard Model. The goal of the current experiment is to significantly improve the measurement sensitivity to the neutron EDM over what is reported in the literature. The experiment has the potential to either measure the magnitude of the neutron EDM or to lower the current experimental limit by two orders of magnitude. Achieving these objectives will have a major impact on our understanding of the physics of both weak and strong interactions. PMID:27308116

Organophosphate degrading microorganisms and enzymes as biocatalysts in environmental and personal decontamination applications.

PubMed

Yair, Simo; Ofer, Butnaro; Arik, Eisenkraft; Shai, Shrot; Yossi, Rosman; Tzvika, Dushnitsky; Amir, Krivoy

2008-01-01

One of the major challenges in dealing with chemical warfare agent (CWA) dispersal, whether in the battlefield or after a terror act, is decontamination and rehabilitation of any contaminated area. Organophosphates (OPs) are considered to be among the deadliest CWAs to date. Other OPs are used as pesticides in modern agriculture, and are considered environmentally hazardous. Current methods for OP decontamination are either dangerous or insufficiently effective. As a promising solution for this problem, bioremediation--the use of biocomponents for environmental remediation--is a potentially effective, safe, and environment-friendly method. The technology relies on several enzymatic mechanisms, and can be applied in various ways. We will review recent achievements and potential applications, such as biocatalyst-containing foams and an enzymatic sponge, for environmental as well as personal exterior decontamination.

iPSCs-based anti-aging therapies: Recent discoveries and future challenges.

PubMed

Pareja-Galeano, Helios; Sanchis-Gomar, Fabián; Pérez, Laura M; Emanuele, Enzo; Lucia, Alejandro; Gálvez, Beatriz G; Gallardo, María Esther

2016-05-01

The main biological hallmarks of the aging process include stem cell exhaustion and cellular senescence. Consequently, research efforts to treat age-related diseases as well as anti-aging therapies in general have recently focused on potential 'reprogramming' regenerative therapies. These new approaches are based on induced pluripotent stem cells (iPSCs), including potential in vivo reprogramming for tissue repair. Another possibility is targeting pathways of cellular senescence, e.g., through modulation of p16INK4a signaling and especially inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Here, we reviewed and discussed these recent developments together with their possible usefulness for future treatments against sarcopenia, a major age-related condition. Copyright © 2016 Elsevier B.V. All rights reserved.

Design of an Information System for Palliative Care: User Analysis.

PubMed

Alvarez-Tobón, Veronica A; Luna-Gómez, Ivan F; Torres-Silva, Ever A; Florez-Arango, Jose F; Rivera-Mejia, Paula T; Higuita Usuga, Andrea

2018-01-01

To explore the demographic factors and the level of knowledge related to information and communication technologies of potential users of a palliative care information system. The Task, User, Representation, Functionality (TURF) framework was applied to characterize potential users (patients and caregivers) of an information system for palliative care in a private clinic in Medellin, Colombia, through a survey. We analyzed 35 patients and 39 caregivers. The majority were women, that lived in urban area and belonged to middle-income socioeconomic stratum. Caregivers, in contrast to patients, are common users of information and communication technologies. An information system should focus on the needs of caregivers, and it would be targeted to subjects facing challenges related to technology adoption; information and communication technologies are interesting and important tools for the improvement of health team.

Approach and Issues Relating to Shield Material Design to Protect Astronauts from Space Radiation

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Cucinotta, F. A.; Miller, J.; Shinn, J. L.; Thibeault, S. A.; Singleterry, R. C.; Simonsen, L. C.; Kim, M. H.

2001-01-01

One major obstacle to human space exploration is the possible limitations imposed by the adverse effects of long-term exposure to the space environment. Even before human spaceflight began, the potentially brief exposure of astronauts to the very intense random solar energetic particle (SEP) events was of great concern. A new challenge appears in deep space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays (GCR) since the missions are of long duration and the accumulated exposures can be high. Since aluminum (traditionally used in spacecraft to avoid potential radiation risks) leads to prohibitively expensive mission launch costs, alternative materials need to be explored. An overview of the materials related issues and their impact on human space exploration will be given.

An integrated fit-for-the-use assessment of marine data adequacy in the Baltic Sea

NASA Astrophysics Data System (ADS)

She, Jun; Novellino, Antonio

2017-04-01

The value of data can only be realized when they are used. Therefore one major factor to determine the extent of the value of data is their level of "fitness-for-the-use". The purpose of the Baltic Sea Check Point project is to assess adequacy of the Baltic Sea data in areas of air, water, biota, seabed and human activities for their usages in social-economic benefit areas and marine knowledge generation, which are presented by eleven challenge areas. The data assessed focused mainly on in situ observations but also include satellite observations, model data, human activity data and integrated data by combining models and observations. The eleven challenge areas are wind farm siting, marine protected areas, oil platform leak, climate change, coastal protection, fishery management, fishery impact, eutrophication, riverine inputs, bathymetry and alien species. The assessment is mainly qualitative with focus on the availability and accessibility, e.g. completeness, coverage, resolution and precision when using the data for pre-defined tasks in each challenge areas, e.g., wind farm site suitability design, generate 100 year time series of sea level for the Baltic coastal stretches etc. The procedure of the assessment is taken in four steps: i) to describe the pre-defined data use cases and objectives; ii) to specify data requirements in performing the data use cases; iii) to investigate the data availability and iv) to assess the data adequacy in terms of the "fitness-for-the-use" of data in the selected challenge areas by comparing the data availability with the data requirements. Due to the complexity involved in the assessment, in-situ observations, especially those from EMODnet, are given more focus than other datasets although all the potential data sources from national, regional and European levels are taken into account. For each challenge area, data adequacy for key variables is assessed and outcomes will be reported. Recommendations for major data gaps, priorities for future observations will also be given.The developed web platform for challenges products and assessment will be also presented.

Exposing the Challenges and Coping Strategies of Field-Ecology Graduate Students

NASA Astrophysics Data System (ADS)

Leon-Beck, Mika; Dodick, Jeff

2012-11-01

In this paper, we expose the unique challenges confronting graduate field-ecology students and the coping strategies they adopt to overcome such challenges. To do so, we used a qualitative (in vivo) research method that combines interviews, observations and open questionnaires with a group of five Israeli graduate students. The two major challenges that the students faced were the uncontrolled nature of field research (or complexity), and the nature of field setting, which isolated the students from authoritative guidance. In response to these challenges, the students developed a set of research skills which were expressed in this study by a series of three (metacognitive) strategies which we designated as 'protocol-dominated', 'intermediate' or 'field-dominated'. In order to develop such research skills, our subjects rely upon declarative and procedural knowledge. In contrast to declarative knowledge, learned in coursework, procedural knowledge is learned and activated via the situated experience of implementing research in authentic field environments. We also found that fieldwork complexity imposes itself the minute the students step into the field; potentially, this can negatively impact students' motivation. However, as the students accumulate field experience and acquire the knowledge and skills needed to overcome the field's complexity, their motivation improves. Recognizing the unique learning components connected to field research will help novice students better cope with fieldwork challenges, as well as help their advisers in guiding them. This work also has implications for designing inquiry curricula in field sciences for university and high-school students.

Evaluation of the safety and adjuvant effect of a detoxified listeriolysin O mutant on the humoral response to dengue virus antigens

PubMed Central

Hernández‐Flores, K. G.; Calderón‐Garcidueñas, A. L.; Mellado‐Sánchez, G.; Ruiz‐Ramos, R.; Sánchez‐Vargas, L. A.; Thomas‐Dupont, P.; Izaguirre‐Hernández, I. Y.; Téllez‐Sosa, J.; Martínez‐Barnetche, J.; Wood, L.; Paterson, Y.; Cedillo‐Barrón, L.; López‐Franco, O.

2017-01-01

Summary Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro‐apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non‐cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and proinflammatory property of the toxoid. Our in‐vivo results in the murine model confirmed that dtLLO is a safer molecule than wild‐type LLO (wtLLO), with a significantly increased survival rate for mice challenged with dtLLO compared with mice challenged with wtLLO (P < 0·001). Histopathological analysis showed non‐toxic effects in key target organs such as brain, heart, liver, spleen, kidney and lung after challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma membrane cholesterol on the surface of murine and human immune cells. Immunization of 6–8‐week‐old female BALB/c mice with a combination of dtLLO mixed with E protein elicited a robust specific humoral response with isotype diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we demonstrated that cholesterol and lipid raft integrity are required to induce a proinflammatory response by human cells. Taken together, these findings support a potential use of the dtLLO mutant as a safe and effective adjuvant molecule in vaccination. PMID:27886660

Evaluation of the safety and adjuvant effect of a detoxified listeriolysin O mutant on the humoral response to dengue virus antigens.

PubMed

Hernández-Flores, K G; Calderón-Garcidueñas, A L; Mellado-Sánchez, G; Ruiz-Ramos, R; Sánchez-Vargas, L A; Thomas-Dupont, P; Izaguirre-Hernández, I Y; Téllez-Sosa, J; Martínez-Barnetche, J; Wood, L; Paterson, Y; Cedillo-Barrón, L; López-Franco, O; Vivanco-Cid, H

2017-04-01

Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro-apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and proinflammatory property of the toxoid. Our in-vivo results in the murine model confirmed that dtLLO is a safer molecule than wild-type LLO (wtLLO), with a significantly increased survival rate for mice challenged with dtLLO compared with mice challenged with wtLLO (P < 0·001). Histopathological analysis showed non-toxic effects in key target organs such as brain, heart, liver, spleen, kidney and lung after challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma membrane cholesterol on the surface of murine and human immune cells. Immunization of 6-8-week-old female BALB/c mice with a combination of dtLLO mixed with E protein elicited a robust specific humoral response with isotype diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we demonstrated that cholesterol and lipid raft integrity are required to induce a proinflammatory response by human cells. Taken together, these findings support a potential use of the dtLLO mutant as a safe and effective adjuvant molecule in vaccination. © 2016 British Society for Immunology.

Genetic heterogeneity in cholangiocarcinoma: a major challenge for targeted therapies

PubMed Central

Brandi, Giovanni; Farioli, Andrea; Astolfi, Annalisa; Biasco, Guido; Tavolari, Simona

2015-01-01

Cholangiocarcinoma (CC) encompasses a group of related but distinct malignancies whose lack of a stereotyped genetic signature makes challenging the identification of genomic landscape and the development of effective targeted therapies. Accumulated evidences strongly suggest that the remarkable genetic heterogeneity of CC may be the result of a complex interplay among different causative factors, some shared by most human cancers while others typical of this malignancy. Currently, considerable efforts are ongoing worldwide for the genetic characterization of CC, also using advanced technologies such as next-generation sequencing (NGS). Undoubtedly this technology could offer an unique opportunity to broaden our understanding on CC molecular pathogenesis. Despite this great potential, however, the high complexity in terms of factors potentially contributing to genetic variability in CC calls for a more cautionary application of NGS to this malignancy, in order to avoid possible biases and criticisms in the identification of candidate actionable targets. This approach is further justified by the urgent need to develop effective targeted therapies in this disease. A multidisciplinary approach integrating genomic, functional and clinical studies is therefore mandatory to translate the results obtained by NGS into effective targeted therapies for this orphan disease. PMID:26142706

The Development of Titanium Alloys for Application in the Space Shuttle Main Engine

NASA Technical Reports Server (NTRS)

Halchak, John A.; Jerman, Gregory A.; Zimmerman, Frank R.

2010-01-01

The high-strength-to-weight ratio of titanium alloys, particularly at cryogenic temperatures, make them attractive for application in rocket engines - offering the potential of superior performance while minimizing component weight. This was particularly attractive for rotating components, such as pump impellers, where titanium alloys presented the potential to achieve a major advance in rotational tip speed, with a reduction in stages and resultant saving in pump weight and complexity. The investigation into titanium alloys for application in cryogenic turbopumps began in the early 1960's. However, it was found that the reactivity of titanium limited applications and produced unique processing challenges. Specialized chemical compositions and processing techniques had to be developed. A substantial amount of material properties testing and trials in experimental turbopumps occurred, ultimately leading to application in the Space Shuttle Main Engine. One particular alloy stood out for use at liquid hydrogen temperatures, Ti-5Al-2.5Sn ELI. This alloy was employed for several critical components. This presentation deals with the development effort, the challenges that were encountered and operational experiences with Ti-5Al-2.5Sn ELI in the SSME.

Microsurgery robots: addressing the needs of high-precision surgical interventions.

PubMed

Mattos, Leonardo S; Caldwell, Darwin G; Peretti, Giorgio; Mora, Francesco; Guastini, Luca; Cingolani, Roberto

2016-01-01

Robotics has a significant potential to enhance the overall capacity and efficiency of healthcare systems. Robots can help surgeons perform better quality operations, leading to reductions in the hospitalisation time of patients and in the impact of surgery on their postoperative quality of life. In particular, robotics can have a significant impact on microsurgery, which presents stringent requirements for superhuman precision and control of the surgical tools. Microsurgery is, in fact, expected to gain importance in a growing range of surgical specialties as novel technologies progressively enable the detection, diagnosis and treatment of diseases at earlier stages. Within such scenarios, robotic microsurgery emerges as one of the key components of future surgical interventions, and will be a vital technology for addressing major surgical challenges. Nonetheless, several issues have yet to be overcome in terms of mechatronics, perception and surgeon-robot interfaces before microsurgical robots can achieve their full potential in operating rooms. Research in this direction is progressing quickly and microsurgery robot prototypes are gradually demonstrating significant clinical benefits in challenging applications such as reconstructive plastic surgery, ophthalmology, otology and laryngology. These are reassuring results offering confidence in a brighter future for high-precision surgical interventions.

The changing face of hemostasis testing in modern laboratories: consolidation, automation, and beyond.

PubMed

Lippi, Giuseppe; Plebani, Mario; Favaloro, Emmanuel J

2015-04-01

The reality of laboratory diagnostics as a whole, and hemostasis testing in particular, is evolving under new paradigms of efficiency. The driving forces of health care and laboratory diagnostics in the third millennium are mainly represented by macro- and microeconomics. In a world with limited resources, shattered by an unprecedented economic crisis, laboratory diagnostics is undergoing a substantial reorganization, with emergence of new models under the imperative of terms, such as bedside testing, consolidation, and networking. The paradigms under which these changes are being developed include a variety of environment, preanalytical, technological, professional, and health-care aspects. The maintenance of continued quality is indeed the major challenge to be faced in the foreseeable future. In fact, some challenges prepotently emerge during a consolidation process, which basically involve delayed testing, centrifugation, transportation, and stability of the specimens, as well as the potential mismatch of sample matrix. This article is aimed to provide an overview of the current economic scenario of laboratory diagnostics and discuss the changing face of hemostasis testing in modern laboratories, providing a synthetic overview about potential drawbacks of actualized solutions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Natural Language Processing in Radiology: A Systematic Review.

PubMed

Pons, Ewoud; Braun, Loes M M; Hunink, M G Myriam; Kors, Jan A

2016-05-01

Radiological reporting has generated large quantities of digital content within the electronic health record, which is potentially a valuable source of information for improving clinical care and supporting research. Although radiology reports are stored for communication and documentation of diagnostic imaging, harnessing their potential requires efficient and automated information extraction: they exist mainly as free-text clinical narrative, from which it is a major challenge to obtain structured data. Natural language processing (NLP) provides techniques that aid the conversion of text into a structured representation, and thus enables computers to derive meaning from human (ie, natural language) input. Used on radiology reports, NLP techniques enable automatic identification and extraction of information. By exploring the various purposes for their use, this review examines how radiology benefits from NLP. A systematic literature search identified 67 relevant publications describing NLP methods that support practical applications in radiology. This review takes a close look at the individual studies in terms of tasks (ie, the extracted information), the NLP methodology and tools used, and their application purpose and performance results. Additionally, limitations, future challenges, and requirements for advancing NLP in radiology will be discussed. (©) RSNA, 2016 Online supplemental material is available for this article.

Educational Leadership: Key Challenges and Ethical Tensions

ERIC Educational Resources Information Center

Duignan, Patrick

2007-01-01

"Educational Leadership" is a major research book on contemporary leadership challenges for educational leaders. In this groundbreaking new work, educational leaders in schools, including teachers, are provided with ways of analysing and resolving common but complex leadership challenges. Ethical tensions inherent in these challenges are…

A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge.

PubMed

Bolhaar, S T H P; Zuidmeer, L; Ma, Y; Ferreira, F; Bruijnzeel-Koomen, C A F M; Hoffmann-Sommergruber, K; van Ree, R; Knulst, A C

2005-12-01

Allergen-specific immunotherapy for food allergy has been hindered by severe side-effects in the past. Well-characterized hypo-allergenic recombinant food allergens potentially offer a safe solution. To demonstrate hypo-allergenicity of a mutated major food allergen from apple, Mal d 1, in vitro and in vivo. A mutant of the major apple allergen, Mal d 1, was obtained by site-directed mutagenesis exchanging five amino acid residues. Fourteen patients with combined birch pollen-related apple allergy were included in the study. Hypo-allergenicity of the mutant rMal d 1 (rMal d 1mut) compared with rMal d 1 was assessed by in vitro methods, i.e. RAST (inhibition), immunoblotting and basophil histamine release (BHR) and in vivo by skin prick test and double-blind placebo-controlled food challenge (DBPCFC). RAST analysis (n = 14) revealed that IgE reactivity to rMal d 1mut was twofold lower than that of the wild-type molecule (95% confidence interval (CI): 1.7-2.4). RAST inhibition (n = 6) showed a 7.8-fold decrease in IgE-binding potency (95% CI: 3.0-12.6). In contrast to this moderate decrease in IgE-binding potency, the biological activity of rMal d 1mut assessed by SPT and BHR decreased 10-200-fold. Hypo-allergenicity was confirmed by DBPCFC (n = 2) with both recombinant molecules. A moderate decrease in IgE-binding potency translates into a potent inhibition of biological activity. This is the first study that confirms by DBPCFC that a mutated recombinant major food allergen is clinically hypo-allergenic. This paves the way towards safer immunotherapy for the treatment of food-allergic patients.

Management in biophotonics and biotechnologies

NASA Astrophysics Data System (ADS)

Meglinski, I. V.; Tuchin, V. V.

2005-10-01

Biophotonics, one of the most exciting and rapidly growing areas, offers vast potential for changing traditional approaches to meeting many critical needs in medicine, biology, pharmacy, food, health care and cosmetic industries. Follow the market trends we developed new MSc course Management in Biophotonics and Biotechnologies (MBB) that provide students of technical disciplines with the necessary training, education and problem-solving skills to produce professionals and managers who are better equipped to handle the challenges of modern science and business in biophotonics and biotechnology. A major advantage of the course is that it provides skills not currently available to graduates in other Master programs.

The impact of globalization on vaccine development and availability.

PubMed

Milstien, Julie B; Kaddar, Miloud; Kieny, Marie Paule

2006-01-01

Globalization is likely to affect many aspects of public health, one of which is vaccine-preventable communicable diseases. Important forces include increased funding initiatives supporting immunization at the global level; regulatory harmonization; widespread intellectual property rights provisions through the World Trade Organization agreements; the emergence of developing-country manufacturers as major players in vaccine supply; and the appearance of new communicable disease threats, including those potentially linked to bioterrorism. All of these forces can affect, either positively and negatively, the development and availability of vaccines. Harnessing these will be a challenge for policymakers and immunization stakeholders.

Patient-centered primary health care: synergy potential for health systems strengthening.

PubMed

Stender, S C; Christensen, A

2013-10-01

The ultimate goal of government health systems is to provide highly effective equitable services that save lives and reduce morbidity and mortality. The pressure to conform to duplicative global and donor initiatives compounds existing challenges to health systems strengthening such as shortages of human resources for health, weak supply chains, inadequate laboratory services and parallel data management systems. This article illustrates how primary health care, as the point of entry into the health care system for the majority of individuals in sub-Saharan Africa, should be strengthened to ensure that individuals and their communities receive essential, holistic care.

Advances in evidence-based cancer adoptive cell therapy.

PubMed

Ge, Chunlei; Li, Ruilei; Song, Xin; Qin, Shukui

2017-04-01

Adoptive cell therapy (ACT) has been developed in cancer treatment by transferring/infusing immune cells into cancer patients, which are able to recognize, target, and destroy tumor cells. Recently, sipuleucel-T and genetically-modified T cells expressing chimeric antigen receptors (CAR) show a great potential to control metastatic castration-resistant prostate cancer and hematologic malignancies in clinic. This review summarized some of the major evidence-based ACT and the challenges to improve cell quality and reduce the side effects in the field. This review also provided future research directions to make sure ACT widely available in clinic.

Cuba Country Analysis Brief

EIA Publications

2016-01-01

Cuba imports the majority of their energy needs, but offshore oil and gas potential could help mitigate their reliance imports. Cuba has entered into many agreements with various countries to help with exploration and drilling efforts. As a result of the ongoing U.S. trade embargo against Cuba, U.S. companies are unable to own any Cuban oil assets. However, U.S. oil companies are allowed to participate in drilling as well as sending technology and supplies with an executive license. While there is interest in Cuban offshore assets, the combination of low oil prices and technically challenging fields could be stumbling blocks for foreign investment.

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

Park, J.; Ahn, Y.; Tilka, J. A.

Disorder in the potential-energy landscape presents a major obstacle to the more rapid development of semiconductor quantum device technologies. We report a large-magnitude source of disorder, beyond commonly considered unintentional background doping or fixed charge in oxide layers: nanoscale strain fields induced by residual stresses in nanopatterned metal gates. Quantitative analysis of synchrotron coherent hard x-ray nanobeam diffraction patterns reveals gate-induced curvature and strains up to 0.03% in a buried Si quantum well within a Si/SiGe heterostructure. Furthermore, electrode stress presents both challenges to the design of devices and opportunities associated with the lateral manipulation of electronic energy levels.

Changes in Space Food over the Last 45 Years

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Lane, Helen W.; Kloeris, Vickie; Perchonok, Michele; Zwart, Sara

2006-01-01

The space food system has improved over the last 45 years. With the advances for a Moon base, there is a potential that foods in space will be more like home cooked foods. However, until that happens, there will continue to be dehydrated and thermostablized foods providing the bulk of the astronauts food. In order for the astronauts to have adequate macronutrients, a food system must be developed including raising plants and food preparation, both a major challenge given the limited water, volume, and power. The lunar kitchens will be very different, but good food is essential to maintain good health.

Novel bioprinting method using a pectin based bioink.

PubMed

Banks, Amanda; Guo, Xiaoru; Chen, Junhong; Kumpaty, Subha; Zhang, Wujie

2017-08-09

One major challenge of bioprinting is to develop a viable bioink to act as an extracellular matrix. This study investigated a novel method for bioprinting using a pectin based bioink. Besides pectin, Pluronic® F-127 was incorporated into the bioink to obtain the desired shape during the initial bioprinting process at 37∘C. Once an object was printed it was treated with Ca2+ (pectin cross-linker) to create the final tissue/organ structure. The results indicated that pectin/Pluronic® F-127 is a potential bioink. Moreover, this methodology provides a novel and fast approach for bioprinting.

Climate Change and Sea Level Rise: A Challenge to Science and Society

NASA Astrophysics Data System (ADS)

Plag, H.

2009-12-01

Society is challenged by the risk of an anticipated rise of coastal Local Sea Level (LSL) as a consequence of future global warming. Many low-lying and often subsiding and densely populated coastal areas are under risk of increased inundation, with potentially devastating consequences for the global economy, society, and environment. Faced with a trade-off between imposing the very high costs of coastal protection and adaptation upon today's national economies and leaving the costs of potential major disasters to future generations, governments and decision makers are in need of scientific support for the development of mitigation and adaptation strategies for the coastal zone. Low-frequency to secular changes in LSL are the result of many interacting Earth system processes. The complexity of the Earth system makes it difficult to predict Global Sea Level (GSL) rise and, even more so, LSL changes over the next 100 to 200 years. Humans have re-engineered the planet and changed major features of the Earth surface and the atmosphere, thus ruling out extrapolation of past and current changes into the future as a reasonable approach. The risk of rapid changes in ocean circulation and ice sheet mass balance introduces the possibility of unexpected changes. Therefore, science is challenged with understanding and constraining the full range of plausible future LSL trajectories and with providing useful support for informed decisions. In the face of largely unpredictable future sea level changes, monitoring of the relevant processes and development of a forecasting service on realistic time scales is crucial as decision support. Forecasting and "early warning" for LSL rise would have to aim at decadal time scales, giving coastal managers sufficient time to react if the onset of rapid changes would require an immediate response. The social, environmental, and economic risks associated with potentially large and rapid LSL changes are enormous. Therefore, in the light of the current uncertainties and the unpredictable nature of some of the forcing processes for LSL changes, the focus of scientific decision support may have to shift from projections of LSL trajectories on century time scales to the development of models and monitoring systems for a forecasting service on decadal time scales. The requirements for such a LSL forecasting service and the current obstacles will be discussed.

The importance of fungi and mycology for addressing major global challenges*.

PubMed

Lange, Lene

2014-12-01

In the new bioeconomy, fungi play a very important role in addressing major global challenges, being instrumental for improved resource efficiency, making renewable substitutes for products from fossil resources, upgrading waste streams to valuable food and feed ingredients, counteracting life-style diseases and antibiotic resistance through strengthening the gut biota, making crop plants more robust to survive climate change conditions, and functioning as host organisms for production of new biological drugs. This range of new uses of fungi all stand on the shoulders of the efforts of mycologists over generations: the scientific discipline mycology has built comprehensive understanding within fungal biodiversity, classification, evolution, genetics, physiology, ecology, pathogenesis, and nutrition. Applied mycology could not make progress without this platform. To unfold the full potentials of what fungi can do for both environment and man we need to strengthen the field of mycology on a global scale. The current mission statement gives an overview of where we are, what needs to be done, what obstacles to overcome, and which potentials are within reach. It further provides a vision for how mycology can be strengthened: The time is right to make the world aware of the immense importance of fungi and mycology for sustainable global development, where land, water and biological materials are used in a more efficient and more sustainable manner. This is an opportunity for profiling mycology by narrating the role played by fungi in the bioeconomy. Greater awareness and appreciation of the role of fungi can be used to build support for mycology around the world. Support will attract more talent to our field of study, empower mycologists around the world to generate more funds for necessary basic research, and strengthen the global mycology network. The use of fungi for unlocking the full potentials of the bioeconomy relies on such progress. The fungal kingdom can be an inspiration for even more.

Friction Stir Additive Manufacturing: Route to High Structural Performance

NASA Astrophysics Data System (ADS)

Palanivel, S.; Sidhar, H.; Mishra, R. S.

2015-03-01

Aerospace and automotive industries provide the next big opportunities for additive manufacturing. Currently, the additive industry is confronted with four major challenges that have been identified in this article. These challenges need to be addressed for the additive technologies to march into new frontiers and create additional markets. Specific potential success in the transportation sectors is dependent on the ability to manufacture complicated structures with high performance. Most of the techniques used for metal-based additive manufacturing are fusion based because of their ability to fulfill the computer-aided design to component vision. Although these techniques aid in fabrication of complex shapes, achieving high structural performance is a key problem due to the liquid-solid phase transformation. In this article, friction stir additive manufacturing (FSAM) is shown as a potential solid-state process for attaining high-performance lightweight alloys for simpler geometrical applications. To illustrate FSAM as a high-performance route, manufactured builds of Mg-4Y-3Nd and AA5083 are shown as examples. In the Mg-based alloy, an average hardness of 120 HV was achieved in the built structure and was significantly higher than that of the base material (97 HV). Similarly for the Al-based alloy, compared with the base hardness of 88 HV, the average built hardness was 104 HV. A potential application of FSAM is illustrated by taking an example of a simple stiffener assembly.

Stereotype Threat: A Qualitative Study of the Challenges Facing Female Undergraduate Engineering Students

NASA Astrophysics Data System (ADS)

Entsminger, J. R., II

From a sociocultural point of view, this qualitative case study explored how upper-level, female undergraduate engineering students perceived the possibility of or experience with stereotype threat as shaping their experiences. The study also investigated how these students explained their reasons for choosing their engineering major, the challenges they encountered in the major, and their reasons for persevering in spite of those challenges. Using Steele and Aronson's (1995) stereotype threat theory as a framework, and considering the documented underrepresentation of females in engineering, the study sought to examine how stereotype threat shaped the experiences of these students and if stereotype threat could be considered a valid reason for the underrepresentation. The study was conducted at a large, four-year public university. First, students in the College of Engineering and Engineering Technology completed the Participant Screening Survey. Based on responses from the survey, six female engineering students from the college were identified and invited to participate in the study. The participants came from the following majors: Electrical Engineering, Industrial and Systems Engineering, and Mechanical Engineering. After receiving the study consent letter and agreeing to participate, the students were involved in a 90-minute focus group meeting, a 45-minute one-on-one interview, and a 30-minute follow-up interview. After conducting the data collection methods, the data were then transcribed, analyzed, and coded for theme development. The themes that emerged coincided with each research question. The themes highlighted the complex interactions and experiences shared by the female engineering majors. The female students were enveloped in an environment where there existed an increased risk for activating stereotype threat. In addition, the female students described feeling pushed to prove to themselves and to others that the negative stereotype that 'females are bad at engineering' was untrue. The findings illustrated the need for systematic changes at the university level. Intervention recommendations were provided. In regards to female underrepresentation in science fields, including engineering, stereotype threat certainly had the potential to cause the female students to question themselves, their abilities, their choice of an academic major, and subsequently remove themselves from a hostile learning or working environment. Thus, educational institutions and workplace organizations are responsible for not only educating themselves regarding stereotype threat, but also for taking steps to alleviate the pernicious effects of stereotype threat.

Development of live attenuated Streptococcus agalactiae as potential vaccines by selecting for resistance to sparfloxacin.

PubMed

Pridgeon, Julia W; Klesius, Phillip H

2013-05-31

To develop attenuated bacteria as potential live vaccines, sparfloxacin was used in this study to modify 40 isolates of Streptococcus agalactiae. Majority of S. agalactiae used in this study were able to develop at least 80-fold resistance to sparfloxacin. When the virulence of the sparfloxacin-resistant S. agalactiae isolates were tested in 10-12g Nile tilapia by intraperitoneal injection at dose of 2×10(7)CFU/fish, 31 were found to be avirulent to fish. Of the 31 avirulent sparfloxacin-resistant S. agalactiae isolates, 30 provided 75-100% protection to 10-12g Nile tilapia against challenges with a virulent S. agalactiae isolate Sag 50. When the virulence of the 30 sparfloxacin-resistant S. agalactiae isolates was tested in 3-5g Nile tilapia by intraperitoneal injection at dose of 2×10(7)CFU/fish, six were found to be avirulent to 3-5g Nile tilapia. Of the six avirulent sparfloxacin-resistant S. agalactiae isolates, four provided 3-5g Nile tilapia 100% protection against challenges with homologous isolates, including Sag 97-spar isolate that was non-hemolytic. However, Sag 97-spar failed to provide broad cross-protection against challenges with heterologous isolates. When Nile tilapia was vaccinated with a polyvalent vaccine consisting of 30 sparfloxacin-resistant S. agalactiae isolates at dose of 2×10(6)CFU/fish, the polyvalent vaccine provided significant (P<0.001) protection to both 3-5g and 15-20g Nile tilapia against challenges with 30 parent isolates of S. agalactiae. Taken together, our results suggest that a polyvalent vaccine consisting of various strains of S. agalactiae might be essential to provide broader protection to Nile tilapia against infections caused by S. agalactiae. Published by Elsevier Ltd.

Learning for Vocation Apprentice Participation in Work Practice

ERIC Educational Resources Information Center

Lyngsnes, Kitt; Rismark, Marit

2011-01-01

The high drop-out rate in upper secondary education is a major challenge to European and US educational programmes. Upper secondary education in Norway faces a similar challenge, because in recent decades, around one-third of the students drop out of the educational programmes. The majority of the drop-outs are students in vocational programmes,…

Families, Schools, and Major Demographic Trends in the United States

ERIC Educational Resources Information Center

Crosnoe, Robert; Benner, Aprile D.

2012-01-01

Although long-term social change is challenging to study, it is theoretically important because its effects are not immediate and it is not usually powered by major social institutions. Another challenge is that individuals are often only vaguely aware of long-term social changes and do not fully consider how they might be affected personally. As…

Student Attraction, Persistence and Retention in STEM Programs: Successes and Continuing Challenges

ERIC Educational Resources Information Center

Sithole, Alec; Chiyaka, Edward T.; McCarthy, Peter; Mupinga, Davison M.; Bucklein, Brian K.; Kibirige, Joachim

2017-01-01

Low student enrollment and high attrition rates in Science, Technology, Engineering, and Mathematics (STEM) education are major challenges in higher education. Many STEM entrants end-up switching their majors to non-STEM fields, perform poorly relative to their peers in other programs, and/or drop out of college without earning any academic…

Ethical and Safety Issues of Stem Cell-Based Therapy.

PubMed

Volarevic, Vladislav; Markovic, Bojana Simovic; Gazdic, Marina; Volarevic, Ana; Jovicic, Nemanja; Arsenijevic, Nebojsa; Armstrong, Lyle; Djonov, Valentin; Lako, Majlinda; Stojkovic, Miodrag

2018-01-01

Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.

Ethical and Safety Issues of Stem Cell-Based Therapy

PubMed Central

Volarevic, Vladislav; Markovic, Bojana Simovic; Gazdic, Marina; Volarevic, Ana; Jovicic, Nemanja; Arsenijevic, Nebojsa; Armstrong, Lyle; Djonov, Valentin; Lako, Majlinda; Stojkovic, Miodrag

2018-01-01

Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells. PMID:29333086

The final stages of the global eradication of poliomyelitis.

PubMed

Grassly, Nicholas C

2013-08-05

The global incidence of poliomyelitis has dropped by more than 99 per cent since the governments of the world committed to eradication in 1988. One of the three serotypes of wild poliovirus has been eradicated and the remaining two serotypes are limited to just a small number of endemic regions. However, the Global Polio Eradication Initiative (GPEI) has faced a number of challenges in eradicating the last 1 per cent of wild-virus transmission. The polio endgame has also been complicated by the recognition that vaccination with the oral poliovirus vaccine (OPV) must eventually cease because of the risk of outbreaks of vaccine-derived polioviruses. I describe the major challenges to wild poliovirus eradication, focusing on the poor immunogenicity of OPV in lower-income countries, the inherent limitations to the sensitivity and specificity of surveillance, the international spread of poliovirus and resulting outbreaks, and the potential significance of waning intestinal immunity induced by OPV. I then focus on the challenges to eradicating all polioviruses, the problem of vaccine-derived polioviruses and the risk of wild-type or vaccine-derived poliovirus re-emergence after the cessation of oral vaccination. I document the role of research in the GPEI's response to these challenges and ultimately the feasibility of achieving a world without poliomyelitis.

Ebola GP-specific monoclonal antibodies protect mice and guinea pigs from lethal Ebola virus infection.

PubMed

Qiu, Xiangguo; Fernando, Lisa; Melito, P Leno; Audet, Jonathan; Feldmann, Heinz; Kobinger, Gary; Alimonti, Judie B; Jones, Steven M

2012-01-01

Ebola virus (EBOV) causes acute hemorrhagic fever in humans and non-human primates with mortality rates up to 90%. So far there are no effective treatments available. This study evaluates the protective efficacy of 8 monoclonal antibodies (MAbs) against Ebola glycoprotein in mice and guinea pigs. Immunocompetent mice or guinea pigs were given MAbs i.p. in various doses individually or as pools of 3-4 MAbs to test their protection against a lethal challenge with mouse- or guinea pig-adapted EBOV. Each of the 8 MAbs (100 µg) protected mice from a lethal EBOV challenge when administered 1 day before or after challenge. Seven MAbs were effective 2 days post-infection (dpi), with 1 MAb demonstrating partial protection 3 dpi. In the guinea pigs each MAb showed partial protection at 1 dpi, however the mean time to death was significantly prolonged compared to the control group. Moreover, treatment with pools of 3-4 MAbs completely protected the majority of animals, while administration at 2-3 dpi achieved 50-100% protection. This data suggests that the MAbs generated are capable of protecting both animal species against lethal Ebola virus challenge. These results indicate that MAbs particularly when used as an oligoclonal set are a potential therapeutic for post-exposure treatment of EBOV infection.

Prevention of work disability due to musculoskeletal disorders: the challenge of implementing evidence.

PubMed

Loisel, Patrick; Buchbinder, Rachelle; Hazard, Rowland; Keller, Robert; Scheel, Inger; van Tulder, Maurits; Webster, Barbara

2005-12-01

The process of returning disabled workers to work presents numerous challenges. In spite of the growing evidence regarding work disability prevention, little uptake of this evidence has been observed. One reason for limited dissemination of evidence is the complexity of the problem, as it is subject to multiple legal, administrative, social, political, and cultural challenges. A literature review and collection of experts' opinion is presented, on the current evidence for work disability prevention, and barriers to evidence implementation. Recommendations are presented for enhancing implementation of research results. The current evidence regarding work disability prevention shows that some clinical interventions (advice to return to modified work and graded activity programs) and some non-clinical interventions (at a service and policy/community level but not at a practice level) are effective in reducing work absenteeism. Implementation of evidence in work disability is a major challenge because intervention recommendations are often imprecise and not yet practical for immediate use, many barriers exist, and many stakeholders are involved. Future studies should involve all relevant stakeholders and aim at developing new strategies that are effective, efficient, and have a potential for successful implementation. These studies should be based upon a clearer conceptualization of the broader context and inter-relationships that determine return to work outcomes.

The final stages of the global eradication of poliomyelitis

PubMed Central

Grassly, Nicholas C.

2013-01-01

The global incidence of poliomyelitis has dropped by more than 99 per cent since the governments of the world committed to eradication in 1988. One of the three serotypes of wild poliovirus has been eradicated and the remaining two serotypes are limited to just a small number of endemic regions. However, the Global Polio Eradication Initiative (GPEI) has faced a number of challenges in eradicating the last 1 per cent of wild-virus transmission. The polio endgame has also been complicated by the recognition that vaccination with the oral poliovirus vaccine (OPV) must eventually cease because of the risk of outbreaks of vaccine-derived polioviruses. I describe the major challenges to wild poliovirus eradication, focusing on the poor immunogenicity of OPV in lower-income countries, the inherent limitations to the sensitivity and specificity of surveillance, the international spread of poliovirus and resulting outbreaks, and the potential significance of waning intestinal immunity induced by OPV. I then focus on the challenges to eradicating all polioviruses, the problem of vaccine-derived polioviruses and the risk of wild-type or vaccine-derived poliovirus re-emergence after the cessation of oral vaccination. I document the role of research in the GPEI's response to these challenges and ultimately the feasibility of achieving a world without poliomyelitis. PMID:23798688

A review on on-board challenges of magnesium-based hydrogen storage materials for automobile applications

NASA Astrophysics Data System (ADS)

Rahman, Md. Wasikur

2017-06-01

The attempt of the review is to realize on-board hydrogen storage technologies concerning magnesium based solid-state matrix to allow fuel cell devices to facilitate sufficient storage capacity, cost, safety and performance requirements to be competitive with current vehicles. Hydrogen, a potential and clean fuel, can be applied in the state-of-the-art technology of `zero emission' vehicles. Hydrogen economy infrastructure both for stationary and mobile purposes is complicated due to its critical physico-chemical properties and materials play crucial roles in every stage of hydrogen production to utilization in fuel cells in achieving high conversion efficiency, safety and robustness of the technologies involved. Moreover, traditional hydrogen storage facilities are rather complicated due to its anomalous properties such as highly porous solids and polymers have intrinsic microporosity, which is the foremost favorable characteristics of fast kinetics and reversibility, but the major drawback is the low storage capacity. In contrast, metal hydrides and complex hydrides have high hydrogen storage capacity but thermodynamically unfavorable. Therefore, hydrogen storage is a real challenge to realize `hydrogen economy' that will solve the critical issues of humanity such as energy depletion, greenhouse emission, air pollution and ultimately climate change. Magnesium based materials, particularly magnesium hydride (MgH2) has been proposed as a potential hydrogen storage material due to its high gravimetric and volumetric capacity as well as environmentally benign properties to work the grand challenge out.

Challenges in engineering osteochondral tissue grafts with hierarchical structures Ivana Gadjanski, Gordana Vunjak Novakovic

PubMed Central

Gadjanski, Ivana; Vunjak-Novakovic, Gordana

2015-01-01

Introduction A major hurdle in treating osteochondral (OC) defects are the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct-engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. Areas covered This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. Expert opinion A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens, and harnessing of inflammatory responses of the host will likely drive the further progress. PMID:26195329

Transducing Airway Basal Cells with a Helper-Dependent Adenoviral Vector for Lung Gene Therapy.

PubMed

Cao, Huibi; Ouyang, Hong; Grasemann, Hartmut; Bartlett, Claire; Du, Kai; Duan, Rongqi; Shi, Fushan; Estrada, Marvin; Seigel, Kyle E; Coates, Allan L; Yeger, Herman; Bear, Christine E; Gonska, Tanja; Moraes, Theo J; Hu, Jim

2018-06-01

A major challenge in developing gene-based therapies for airway diseases such as cystic fibrosis (CF) is sustaining therapeutic levels of transgene expression over time. This is largely due to airway epithelial cell turnover and the host immunogenicity to gene delivery vectors. Modern gene editing tools and delivery vehicles hold great potential for overcoming this challenge. There is currently not much known about how to deliver genes into airway stem cells, of which basal cells are the major type in human airways. In this study, helper-dependent adenoviral (HD-Ad) vectors were delivered to mouse and pig airways via intranasal delivery, and direct bronchoscopic instillation, respectively. Vector transduction was assessed by immunostaining of lung tissue sections, which revealed that airway basal cells of mice and pigs can be targeted in vivo. In addition, efficient transduction of primary human airway basal cells was verified with an HD-Ad vector expressing green fluorescent protein. Furthermore, we successfully delivered the human CFTR gene to airway basal cells from CF patients, and demonstrated restoration of CFTR channel activity following cell differentiation in air-liquid interface culture. Our results provide a strong rationale for utilizing HD-Ad vectors to target airway basal cells for permanent gene correction of genetic airway diseases.

Alternative Test Methods for Developmental Neurotoxicity: A ...

EPA Pesticide Factsheets

Exposure to environmental contaminants is well documented to adversely impact the development of the nervous system. However, the time, animal and resource intensive EPA and OECD testing guideline methods for developmental neurotoxicity (DNT) are not a viable solution to characterizing potential chemical hazards for the thousands of untested chemicals currently in commerce. Thus, research efforts over the past decade have endeavored to develop cost-effective alternative DNT testing methods. These efforts have begun to generate data that can inform regulatory decisions. Yet there are major challenges to both the acceptance and use of this data. Major scientific challenges for DNT include development of new methods and models that are “fit for purpose”, development of a decision-use framework, and regulatory acceptance of the methods. It is critical to understand that use of data from these methods will be driven mainly by the regulatory problems being addressed. Some problems may be addressed with limited datasets, while others may require data for large numbers of chemicals, or require the development and use of new biological and computational models. For example mechanistic information derived from in vitro DNT assays can be used to inform weight of evidence (WoE) or integrated approaches to testing and assessment (IATA) approaches for chemical-specific assessments. Alternatively, in vitro data can be used to prioritize (for further testing) the thousands

Virtual Inertia: Current Trends and Future Directions

DOE PAGES

Tamrakar, Ujjwol; Shrestha, Dipesh; Maharjan, Manisha; ...

2017-06-26

The modern power system is progressing from a synchronous machine-based system towards an inverter-dominated system, with a large-scale penetration of renewable energy sources (RESs) like wind and photovoltaics. RES units today represent a major share of the generation, and the traditional approach of integrating themas grid following units can lead to frequency instability. Many researchers have pointed towards using inverters with virtual inertia control algorithms so that they appear as synchronous generators to the grid, maintaining and enhancing system stability. Our paper presents a literature review of the current state-of-the-art of virtual inertia implementation techniques, and explores potential research directionsmore » and challenges. The major virtual inertia topologies are compared and classified. Through literature review and simulations of some selected topologies it has been shown that similar inertial response can be achieved by relating the parameters of these topologies through time constants and inertia constants, although the exact frequency dynamics may vary slightly. The suitability of a topology depends on system control architecture and desired level of detail in replication of the dynamics of synchronous generators. We present a discussion on the challenges and research directions which points out several research needs, especially for systems level integration of virtual inertia systems.« less

Virtual Inertia: Current Trends and Future Directions

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

Tamrakar, Ujjwol; Shrestha, Dipesh; Maharjan, Manisha

The modern power system is progressing from a synchronous machine-based system towards an inverter-dominated system, with a large-scale penetration of renewable energy sources (RESs) like wind and photovoltaics. RES units today represent a major share of the generation, and the traditional approach of integrating themas grid following units can lead to frequency instability. Many researchers have pointed towards using inverters with virtual inertia control algorithms so that they appear as synchronous generators to the grid, maintaining and enhancing system stability. Our paper presents a literature review of the current state-of-the-art of virtual inertia implementation techniques, and explores potential research directionsmore » and challenges. The major virtual inertia topologies are compared and classified. Through literature review and simulations of some selected topologies it has been shown that similar inertial response can be achieved by relating the parameters of these topologies through time constants and inertia constants, although the exact frequency dynamics may vary slightly. The suitability of a topology depends on system control architecture and desired level of detail in replication of the dynamics of synchronous generators. We present a discussion on the challenges and research directions which points out several research needs, especially for systems level integration of virtual inertia systems.« less

Novel Hamiltonian method for collective dynamics analysis of an intense charged particle beam propagating through a periodic focusing quadrupole lattice a)

NASA Astrophysics Data System (ADS)

Startsev, Edward A.; Davidson, Ronald C.

2011-05-01

Identifying regimes for quiescent propagation of intense beams over long distances has been a major challenge in accelerator research. In particular, the development of systematic theoretical approaches that are able to treat self-consistently the applied oscillating force and the nonlinear self-field force of the beam particles simultaneously has been a major challenge of modern beam physics. In this paper, the recently developed Hamiltonian averaging technique [E. A. Startsev, R. C. Davidson, and M. Dorf, Phys. Rev. ST Accel. Beams 13, 064402 (2010)] which incorporates both the applied periodic focusing force and the self-field force of the beam particles, is generalized to the case of time-dependent beam distributions. The new formulation allows not only a determination of quasi-equilibrium solutions of the non-linear Vlasov-Poison system of equations but also a detailed study of their stability properties. The corrections to the well-known "smooth-focusing" approximation are derived, and the results are applied to a matched beam with thermal equilibrium distribution function. It is shown that the corrections remain small even for moderate values of the vacuum phase advance συ. Nonetheless, because the corrections to the average self-field potential are non-axisymmetric, the stability properties of the different beam quasi-equilibria can change significantly.

[Sudden cardiac death, a major scientific challenge].

PubMed

Haissaguerre, Michel; Hocini, Meleze; Sacher, Frédéric; Shah, Ashok

2010-06-01

Sudden death is responsible for 350,000 deaths each year in Europe, or 1000 deaths each day, equivalent to the combined mortality from the most lethal cancers (breast, lung and colorectal). Unfortunately, sudden death is widely considered to be "natural", being due to unknown but critical cardiac disorders leading to sudden arrest of cardiac activity. Awareness of its potential preventability is inadequate. Indeed, 80% of cases of sudden death are associated with extremely rapid heartbeats, an "electric tornado" called ventricular fibrillation, caused by ultrarapid firing of ectopic foci or chaotic wave propagation. This arrhythmia strikes like lightning Although it can be associated with myocardial infarction, most victims have structurally normal or slightly altered hearts. The cells which cause this ultrarapid firing originate from the Purkinje system, which constitutes just a fraction (2%) of total cardiac mass. This is borne out by the fact that the risk of fatal arrhythmic events can be reduced by focal thermoablation. What is most important is to identify subjects at risk of such events. It has been suggested that there exists an unidentified subclinical electrical disharmony, which converts into a tornado of ultimately fatal clinical events at a certain threshold level. High-resolution bioelectrical cardiac mapping, functional imaging, and treatment of electrical field disorders are major scientific challenges given their complexity, intraindividual dynamics and interindividual variability.

Advances in the delivery of RNA therapeutics: from concept to clinical reality.

PubMed

Kaczmarek, James C; Kowalski, Piotr S; Anderson, Daniel G

2017-06-27

The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.

Magnetoencephalography as a Tool in Psychiatric Research: Current Status and Perspective.

PubMed

Uhlhaas, Peter J; Liddle, Peter; Linden, David E J; Nobre, Anna C; Singh, Krish D; Gross, Joachim

2017-04-01

The application of neuroimaging to provide mechanistic insights into circuit dysfunctions in major psychiatric conditions and the development of biomarkers are core challenges in current psychiatric research. We propose that recent technological and analytic advances in magnetoencephalography (MEG), a technique that allows measurement of neuronal events directly and noninvasively with millisecond resolution, provides novel opportunities to address these fundamental questions. Because of its potential in delineating normal and abnormal brain dynamics, we propose that MEG provides a crucial tool to advance our understanding of pathophysiological mechanisms of major neuropsychiatric conditions, such as schizophrenia, autism spectrum disorders, and the dementias. We summarize the mechanisms underlying the generation of MEG signals and the tools available to reconstruct generators and underlying networks using advanced source-reconstruction techniques. We then surveyed recent studies that have used MEG to examine aberrant rhythmic activity in neuropsychiatric disorders. This was followed by links with preclinical research that has highlighted possible neurobiological mechanisms, such as disturbances in excitation/inhibition parameters, that could account for measured changes in neural oscillations. Finally, we discuss challenges as well as novel methodological developments that could pave the way for widespread application of MEG in translational research with the aim of developing biomarkers for early detection and diagnosis.

Application of ICT in strengthening health information systems in developing countries in the wake of globalisation.

PubMed

Simba, Daudi O; Mwangu, Mughwira

2004-12-01

Information Communication Technology (ICT) revolution brought opportunities and challenges to developing countries in their efforts to strengthen the Health Management Information Systems (HMIS). In the wake of globalisation, developing countries have no choice but to take advantage of the opportunities and face the challenges. The last decades saw developing countries taking action to strengthen and modernise their HMIS using the existing ICT. Due to poor economic and communication infrastructure, the process has been limited to national and provincial/region levels leaving behind majority of health workers living in remote/rural areas. Even those with access do not get maximum benefit from ICT advancements due to inadequacies in data quality and lack of data utilisation. Therefore, developing countries need to make deliberate efforts to address constraints threatening to increase technology gap between urban minority and rural majority by setting up favourable policies and appropriate strategies. Concurrently, strategies to improve data quality and utilisation should be instituted to ensure that HMIS has positive impact on people's health. Potential strength from private sector and opportunities for sharing experiences among developing countries should be utilised. Short of this, advancement in ICT will continue to marginalise health workers in developing countries especially those living in remote areas.

How to Recharge a Confined Aquifer: An Exploration of Geologic Controls on Groundwater Storage.

NASA Astrophysics Data System (ADS)

Maples, S.; Fogg, G. E.; Maxwell, R. M.; Liu, Y.

2017-12-01

Decreased snowpack storage and groundwater overdraft in California has increased interest in managed aquifer recharge (MAR) of excess winter runoff to the Central Valley aquifer system, which has unused storage capacity that far exceeds the state's surface reservoirs. Recharge to the productive, confined aquifer system remains a challenge due to the presence of nearly-ubiquitous, multiple silt and clay confining units that limit recharge pathways. However, previous studies have identified interconnected networks of sand and gravel deposits that bypass the confining units and accommodate rapid, high-volume recharge to the confined aquifer system in select locations. We use the variably-saturated, fully-integrated groundwater/surface-water flow code, ParFlow, in combination with a high-resolution, transition probability Markov-chain geostatistical model of the subsurface geologic heterogeneity of the east side of the Sacramento Valley, CA, to characterize recharge potential across a landscape that includes these geologic features. Multiple 180-day MAR simulations show that recharge potential is highly dependent on subsurface geologic structure, with a several order-of-magnitude range of recharge rates and volumes across the landscape. Where there are recharge pathways to the productive confined-aquifer system, pressure propagation in the confined system is widespread and rapid, with multi-kilometer lateral pressure propagation. Although widespread pressure propagation occurs in the confined system, only a small fraction of recharge volume is accommodated there. Instead, the majority of recharge occurs by filling unsaturated pore spaces. Where they outcrop at land surface, high-K recharge pathways fill rapidly, accommodating the majority of recharge during early time. However, these features become saturated quickly, and somewhat counterintuitively, the low-K silt and clay facies accommodate the majority of recharge volume during most of the simulation. These findings (1) highlight the large variability of MAR potential across the landscape, wherein the recharge capacity in select areas far exceeds recharge potential over most of the landscape, and (2) elucidate important physical processes that control MAR potential in alluvial aquifer systems.

Respiratory medicine in China: progress, challenges, and opportunities.

PubMed

Wang, Chen; Xiao, Fei; Qiao, Renli; Shen, Ying H

2013-06-01

The past century witnessed a rapid development of respiratory medicine in China. The major burden of respiratory disease has shifted from infectious diseases to chronic noninfectious diseases. Great achievements have been made in improving the national standard of clinical management of various respiratory diseases and in smoking control. The specialty of respiratory medicine is expanding into pulmonary and critical care medicine. Nevertheless, respiratory diseases remain a major public health problem, with new challenges such as air pollution and nosocomial infections. This review describes the history, accomplishments, new challenges, and opportunities in respiratory medicine in China.

Plant-made oral vaccines against human infectious diseases—Are we there yet?

PubMed Central

Chan, Hui-Ting; Daniell, Henry

2016-01-01

Summary Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches. PMID:26387509

Evaluation of international recruitment of health professionals in England.

PubMed

Young, Ruth; Noble, Jenny; Mahon, Ann; Maxted, Mairead; Grant, Janet; Sibbald, Bonnie

2010-10-01

To explore whether a period of intensive international recruitment by the English National Health Service (NHS) achieved its objectives of boosting workforce numbers and to set this against the wider costs, longer-term challenges and questions arising. A postal survey of all pre-2006 NHS providers, Strategic Health Authorities and Deans of Postgraduate Medical Education obtained information on 284 (45%) organizations (142 completed questionnaires). Eight subsequent case studies (74 interviews) covered medical consultant, general practitioner, nurse, midwife and allied health professional recruitment. Most respondents had undertaken or facilitated international recruitment between 2001 and 2006 and believed that it had enabled them to address immediate staff shortages. Views on longer-term implications, such as recruit retention, were more equivocal. Most organizations had made only a limited value-for-money assessment, balancing direct expenditure on overseas recruitment against savings on temporary staff. Other short and long-term transaction and opportunity costs arose from pressures on existing staff, time spent on induction/pastoral support, and human resource management and workforce planning challenges. Though recognized, these extensive 'hidden costs' for NHS organizations were harder to assess as were the implications for source countries and migrant staff. The main achievement of the intensive international recruitment period from a UK viewpoint was that such a major undertaking was seen through without major disruption to NHS services. The wider costs and challenges meant, however, that large-scale international recruitment was not sustainable as a solution to workforce shortages. Should such approaches be attempted in future, a clearer upfront appraisal of all the potential costs and implications will be vital.

Laboratory Directed Research and Development 1998 Annual Report

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

Pam Hughes; Sheila Bennett eds.

1999-07-14

The Laboratory's Directed Research and Development (LDRD) program encourages the advancement of science and the development of major new technical capabilities from which future research and development will grow. Through LDRD funding, Pacific Northwest continually replenishes its inventory of ideas that have the potential to address major national needs. The LDRD program has enabled the Laboratory to bring to bear its scientific and technical capabilities on all of DOE's missions, particularly in the arena of environmental problems. Many of the concepts related to environmental cleanup originally developed with LDRD funds are now receiving programmatic support from DOE, LDRD-funded work inmore » atmospheric sciences is now being applied to DOE's Atmospheric Radiation Measurement Program. We also have used concepts initially explored through LDRD to develop several winning proposals in the Environmental Management Science Program. The success of our LDRD program is founded on good management practices that ensure funding is allocated and projects are conducted in compliance with DOE requirements. We thoroughly evaluate the LDRD proposals based on their scientific and technical merit, as well as their relevance to DOE's programmatic needs. After a proposal is funded, we assess progress annually using external peer reviews. This year, as in years past, the LDRD program has once again proven to be the major enabling vehicle for our staff to formulate new ideas, advance scientific capability, and develop potential applications for DOE's most significant challenges.« less

Review of Florida's Eminent Scholar and Major Gift Challenge Grant Programs. Report No. 96-01.

ERIC Educational Resources Information Center

Florida State Legislature, Tallahassee. Office of Program Policy Analysis and Government Accountability.

This audit report presents results of a review of the Florida Eminent Scholar and Major Gift Challenge Grant Programs. In four chapters the report: (1) reviews the purpose, scope, and background of the programs; (2) looks at program successes, fees, and expenditures, noting that the programs have raised $219 million in private donations to support…

Oncological image analysis.

PubMed

Brady, Sir Michael; Highnam, Ralph; Irving, Benjamin; Schnabel, Julia A

2016-10-01

Cancer is one of the world's major healthcare challenges and, as such, an important application of medical image analysis. After a brief introduction to cancer, we summarise some of the major developments in oncological image analysis over the past 20 years, but concentrating those in the authors' laboratories, and then outline opportunities and challenges for the next decade. Copyright © 2016 Elsevier B.V. All rights reserved.

Completion of a Full Course of Primary Schooling among All Children Everywhere by 2015: A Case of Sub-Saharan Africa

ERIC Educational Resources Information Center

Wamala, Robert

2013-01-01

Achieving the United Nations Millennium Development Goals (MDGs) remains a major challenge, particularly in developing countries. Specifically, achieving the target of completing a full course of primary schooling among all children, which is goal two, is a major challenge for Sub-Saharan Africa. Though literature consensually suggests that the…

Clicking to Learn: A Case Study of Embedding Radio-Frequency Based Clickers in an Introductory Management Information Systems Course

ERIC Educational Resources Information Center

Nelson, Matthew L.; Hauck, Roslin V.

2008-01-01

The challenges associated with teaching a core introductory management information systems (MIS) course are well known (large class sizes serving a majority of non-MIS majors, sustaining student interests, encouraging class participation, etc.). This study offers a mechanism towards managing these challenges through the use of a simple and…

Critical evaluation of the EU-technical guidance on shelf-life studies for L. monocytogenes on RTE-foods: a case study for smoked salmon.

PubMed

Vermeulen, A; Devlieghere, F; De Loy-Hendrickx, A; Uyttendaele, M

2011-01-31

In November 2008, a technical guidance document on the challenge test protocol was published by the EU CRL (Community of Reference Laboratory) for L. monocytogenes. This document describes the practical aspects on the execution of a challenge test in order to comply to the EU Commission regulation N° 2073/2005 on microbiological criteria for foodstuff. In this guideline two approaches are specified. On the one hand challenge tests, based on actual data measurements at the beginning and end of the shelf-life of products stored under reasonably foreseen T-profile, are described. On the other hand, growth potential is calculated by predictive models using a validated maximum specific growth rate. The present study evaluates the two above mentioned approaches on cold smoked salmon, a typical risk product for L. monocytogenes. The focus is on: (i) the relative importance of intrabatch versus interbatch variability, (ii) the concept of a simple challenge test based on actual data at start and end of shelf life versus a modelling approach and (iii) the interpretation of challenge tests. Next to this, available tertiary models were used to estimate the growth potential of these products based on their initial physicochemical characteristics. From the results it could be concluded that in some batches considerable intrabatch variability was obtained. In general, however, the interbatch variability was significantly higher than intrabatch variability. Concerning the two above mentioned methods for challenge tests, it can be stated that the first approach (simple challenge test) can be set up rather rapidly and is cost-effective for SMEs (small and medium enterprises) but provides only a single isolated outcome. This implies that challenge tests should be redone if changes occur in composition or production process. The second (modelling) approach, using extended challenge tests to establish growth parameters needs larger set ups and more complicated data analysis, which makes them more expensive. Using available tertiary models has the major advantage that the most important intrinsic and extrinsic factors can be included for the prediction of the growth parameter. It was clear that product specific models, taking into account the interaction effects with background flora, performed the best. Regarding the challenge tests, it can be concluded that the best approach to choose will depend on the particular context as in the end both approaches will lead to the same conclusion. Copyright © 2010 Elsevier B.V. All rights reserved.

Changing R&D models in research-based pharmaceutical companies.

PubMed

Schuhmacher, Alexander; Gassmann, Oliver; Hinder, Markus

2016-04-27

New drugs serving unmet medical needs are one of the key value drivers of research-based pharmaceutical companies. The efficiency of research and development (R&D), defined as the successful approval and launch of new medicines (output) in the rate of the monetary investments required for R&D (input), has declined since decades. We aimed to identify, analyze and describe the factors that impact the R&D efficiency. Based on publicly available information, we reviewed the R&D models of major research-based pharmaceutical companies and analyzed the key challenges and success factors of a sustainable R&D output. We calculated that the R&D efficiencies of major research-based pharmaceutical companies were in the range of USD 3.2-32.3 billion (2006-2014). As these numbers challenge the model of an innovation-driven pharmaceutical industry, we analyzed the concepts that companies are following to increase their R&D efficiencies: (A) Activities to reduce portfolio and project risk, (B) activities to reduce R&D costs, and (C) activities to increase the innovation potential. While category A comprises measures such as portfolio management and licensing, measures grouped in category B are outsourcing and risk-sharing in late-stage development. Companies made diverse steps to increase their innovation potential and open innovation, exemplified by open source, innovation centers, or crowdsourcing, plays a key role in doing so. In conclusion, research-based pharmaceutical companies need to be aware of the key factors, which impact the rate of innovation, R&D cost and probability of success. Depending on their company strategy and their R&D set-up they can opt for one of the following open innovators: knowledge creator, knowledge integrator or knowledge leverager.

Putting Technology to Work in Science - How to Select Unmanned Aerial Vehicles (UAV) and their Instrumentation for Atmospheric and Earth Surface Observations

NASA Astrophysics Data System (ADS)

Teller, Amit; Lange, Manfred; Ioannou, Stelios; Keleshis, Christos

2010-05-01

The Autonomous Flying Platforms for Atmospheric and Earth Surface Observations project (APAESO) of the Energy, Environment and Water Research Center (EEWRC) at the Cyprus Institute is aimed at the dual purpose of carrying out atmospheric and earth-surface observations in the Mediterranean. The APAESO platforms will offer the unique potential to determine physical, chemical and radiative atmospheric properties, aerosol and dust concentrations, atmospheric dynamics, surface morphology, vegetation and land use patterns as well as ocean surface properties (biology, waves, currents) and to carry out archaeological site reconnaissance and contaminant detection at high spatial resolution. The first phase of APAESO was dedicated to the preliminary design and the selection of an Unmanned Aerial Vehicle (UAV) as the backbone of the APAESO infrastructure. Selection of a UAV suitable for the many research objectives as outlined above is challenging because the UAV technology is new and rapidly evolving. This notwithstanding, a very large number of systems, mostly utilized for defense purposes, are currently available. The major challenge in the selection process lies in considering the trade-off between different platform characteristics (e.g. payload weight, endurance, max. altitude for operation and price) and in optimizing the potential performance of the UAV. Based on the required characteristics for the UAV platform, a survey of possible UAVs and suitable sensors was prepared based on various data sources. We used an elimination process in order to consider only a few models for the final selection process out of about 1000 commercially available UAV models that were initially investigated. The presentation will discuss the main scientific objectives that determine the specification of the UAV platform, major considerations in selecting best available technology for our needs and will briefly describe the next phases of the project.

Pathogen reduction and blood transfusion safety in Africa: strengths, limitations and challenges of implementation in low-resource settings.

PubMed

Ware, A D; Jacquot, C; Tobian, A A R; Gehrie, E A; Ness, P M; Bloch, E M

2018-01-01

Transfusion-transmitted infection risk remains an enduring challenge to blood safety in Africa. A high background incidence and prevalence of the major transfusion-transmitted infections (TTIs), dependence on high-risk donors to meet demand, suboptimal testing and quality assurance collectively contribute to the increased risk. With few exceptions, donor testing is confined to serological evaluation of human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV) and syphilis. Barriers to implementation of broader molecular methods include cost, limited infrastructure and lack of technical expertise. Pathogen reduction (PR), a term used to describe a variety of methods (e.g. solvent detergent treatment or photochemical activation) that may be applied to blood following collection, offers the means to diminish the infectious potential of multiple pathogens simultaneously. This is effective against different classes of pathogen, including the major TTIs where laboratory screening is already implemented (e.g. HIV, HBV and HCV) as well pathogens that are widely endemic yet remain unaddressed (e.g. malaria, bacterial contamination). We sought to review the available and emerging PR techniques and their potential application to resource-constrained parts of Africa, focusing on the advantages and disadvantages of such technologies. PR has been slow to be adopted even in high-income countries, primarily given the high costs of use. Logistical considerations, particularly in low-resourced parts of Africa, also raise concerns about practicality. Nonetheless, PR offers a rational, innovative strategy to contend with TTIs; technologies in development may well present a viable complement or even alternative to targeted screening in the future. © 2017 International Society of Blood Transfusion.

Metabotropic Glutamate Receptor 5 as a Target for the Treatment of Depression and Smoking: Robust Preclinical Data but Inconclusive Clinical Efficacy.

PubMed

Barnes, Samuel A; Sheffler, Douglas J; Semenova, Svetlana; Cosford, Nicholas D P; Bespalov, Anton

2018-06-01

The ability of novel pharmacological compounds to improve outcomes in preclinical models is often not translated into clinical efficacy. Psychiatric disorders do not have biological boundaries, and identifying mechanisms to improve the translational bottleneck between preclinical and clinical research domains is an important and challenging task. Glutamate transmission is disrupted in several neuropsychiatric disorders. Metabotropic glutamate (mGlu) receptors represent a diverse class of receptors that contribute to excitatory neurotransmission. Given the wide, yet region-specific manner of expression, developing pharmacological compounds to modulate mGlu receptor activity provides an opportunity to subtly and selectively modulate excitatory neurotransmission. This review focuses on the potential involvement of mGlu5 receptor disruption in major depressive disorder and substance and/or alcohol use disorders. We provide an overview of the justification of targeting mGlu5 receptors in the treatment of these disorders, summarize the preclinical evidence for negatively modulating mGlu5 receptors as a therapeutic target for major depressive disorders and nicotine dependence, and highlight the outcomes of recent clinical trials. While the evidence of mGlu5 receptor negative allosteric modulation has been promising in preclinical investigations, these beneficial effects have not translated into clinical efficacy. In this review, we identify key challenges that may contribute to poor clinical translation and provide suggested approaches moving forward to potentially improve the translation from preclinical to clinical domains. Such approaches may increase the success of clinical trials and may reduce the translational bottleneck that exists in drug discovery for psychiatric disorders. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Factors influencing property selection for conservation revolving funds.

PubMed

Hardy, Mathew J; Fitzsimons, James A; Bekessy, Sarah A; Gordon, Ascelin

2018-04-01

Finding sustainable ways to increase the amount of private land protected for biodiversity is challenging for many conservation organizations. In some countries, organizations use revolving-fund programs, whereby land is purchased and then sold to conservation-minded owners under condition they enter into a conservation covenant or easement. The sale proceeds are used to purchase, protect, and sell additional properties, incrementally increasing the amount of protected private land. Because the effectiveness of this approach relies on selecting appropriate properties, we explored factors currently considered by practitioners and how these are integrated into decision making. We conducted exploratory, semistructured interviews with managers from each of the 5 major revolving funds in Australia. Responses indicated although conservation factors are important, financial and social factors are also highly influential. A major determinant was whether the property could be resold within a reasonable period at a price that replenishes the fund. To facilitate resale, often selected properties include the potential for the construction of a dwelling. Practitioners face with clear trade-offs between conservation, financial, amenity, and other factors in selecting properties and 3 main challenges: recovering the costs of acquisition, protection, and resale; reselling the property; and meeting conservation goals. Our findings suggest the complexity of these decisions may constrain revolving-fund effectiveness. Drawing from participant responses, we identified potential strategies to mitigate these risks, such as providing adequate recreational space without jeopardizing ecological assets. We suggest managers could benefit from a shared-learning and adaptive approach to property selection given the commonalities between programs. Understanding how practitioners deal with complex decisions in the implementation of revolving funds helps identify future research to improve the performance of this conservation tool. © 2017 Society for Conservation Biology.

Meeting the challenges of micronutrient malnutrition in the developing world.

PubMed

Bhutta, Zulfiqar A; Salam, Rehana A; Das, Jai K

2013-01-01

Malnutrition still remains one of the major public health challenges, particularly in developing countries. Major risk factors for undernutrition such as suboptimal breastfeeding and micronutrient deficiencies (vitamin A and zinc) are responsible for more than one-third of all under five child deaths and 11% of the global total disease burden. Several strategies have been employed to supplement micronutrients. These include education, dietary modification, food provision, supplementation and fortification either alone or in combination. Supplementation is the most widely practiced intervention while fortification can also be a potentially cost-effective public health intervention and target a larger population through a single strategy. Universal coverage with the full bundle of interventions including micronutrient provision, complementary foods, treatments for worms and diarrheal diseases and behavior change programs package could be the way forward in achieving the Millennium Development Goals (MDGs). Bio-fortification and agricultural interventions including home and school gardening are relatively newer strategies and require further research as they have the potential to impact nutritional status of populations at large. Effectiveness of the various interventions is well recognized; however, consensus needs to be built around approaches to scale up coverage and delivery strategies to reduce disparities and provide equitable access. Future studies should focus on evaluating various approaches to address malnutrition with a standard methodology and defined outcomes. This will help gauge the actual morbidity and mortality impacts of these specific interventions and the long-term viability of these programs. On a broader scale, strategies to address food insecurity and poverty alleviation are the key as these are complex sustainable development issues, linked to health through malnutrition, but also to sustainable economic development, environment and trade.

MACE prediction of acute coronary syndrome via boosted resampling classification using electronic medical records.

PubMed

Huang, Zhengxing; Chan, Tak-Ming; Dong, Wei

2017-02-01

Major adverse cardiac events (MACE) of acute coronary syndrome (ACS) often occur suddenly resulting in high mortality and morbidity. Recently, the rapid development of electronic medical records (EMR) provides the opportunity to utilize the potential of EMR to improve the performance of MACE prediction. In this study, we present a novel data-mining based approach specialized for MACE prediction from a large volume of EMR data. The proposed approach presents a new classification algorithm by applying both over-sampling and under-sampling on minority-class and majority-class samples, respectively, and integrating the resampling strategy into a boosting framework so that it can effectively handle imbalance of MACE of ACS patients analogous to domain practice. The method learns a new and stronger MACE prediction model each iteration from a more difficult subset of EMR data with wrongly predicted MACEs of ACS patients by a previous weak model. We verify the effectiveness of the proposed approach on a clinical dataset containing 2930 ACS patient samples with 268 feature types. While the imbalanced ratio does not seem extreme (25.7%), MACE prediction targets pose great challenge to traditional methods. As these methods degenerate dramatically with increasing imbalanced ratios, the performance of our approach for predicting MACE remains robust and reaches 0.672 in terms of AUC. On average, the proposed approach improves the performance of MACE prediction by 4.8%, 4.5%, 8.6% and 4.8% over the standard SVM, Adaboost, SMOTE, and the conventional GRACE risk scoring system for MACE prediction, respectively. We consider that the proposed iterative boosting approach has demonstrated great potential to meet the challenge of MACE prediction for ACS patients using a large volume of EMR. Copyright © 2017 Elsevier Inc. All rights reserved.

Conservation physiology of marine fishes: state of the art and prospects for policy.

PubMed

McKenzie, David J; Axelsson, Michael; Chabot, Denis; Claireaux, Guy; Cooke, Steven J; Corner, Richard A; De Boeck, Gudrun; Domenici, Paolo; Guerreiro, Pedro M; Hamer, Bojan; Jørgensen, Christian; Killen, Shaun S; Lefevre, Sjannie; Marras, Stefano; Michaelidis, Basile; Nilsson, Göran E; Peck, Myron A; Perez-Ruzafa, Angel; Rijnsdorp, Adriaan D; Shiels, Holly A; Steffensen, John F; Svendsen, Jon C; Svendsen, Morten B S; Teal, Lorna R; van der Meer, Jaap; Wang, Tobias; Wilson, Jonathan M; Wilson, Rod W; Metcalfe, Julian D

2016-01-01

The state of the art of research on the environmental physiology of marine fishes is reviewed from the perspective of how it can contribute to conservation of biodiversity and fishery resources. A major constraint to application of physiological knowledge for conservation of marine fishes is the limited knowledge base; international collaboration is needed to study the environmental physiology of a wider range of species. Multifactorial field and laboratory studies on biomarkers hold promise to relate ecophysiology directly to habitat quality and population status. The 'Fry paradigm' could have broad applications for conservation physiology research if it provides a universal mechanism to link physiological function with ecological performance and population dynamics of fishes, through effects of abiotic conditions on aerobic metabolic scope. The available data indicate, however, that the paradigm is not universal, so further research is required on a wide diversity of species. Fish physiologists should interact closely with researchers developing ecological models, in order to investigate how integrating physiological information improves confidence in projecting effects of global change; for example, with mechanistic models that define habitat suitability based upon potential for aerobic scope or outputs of a dynamic energy budget. One major challenge to upscaling from physiology of individuals to the level of species and communities is incorporating intraspecific variation, which could be a crucial component of species' resilience to global change. Understanding what fishes do in the wild is also a challenge, but techniques of biotelemetry and biologging are providing novel information towards effective conservation. Overall, fish physiologists must strive to render research outputs more applicable to management and decision-making. There are various potential avenues for information flow, in the shorter term directly through biomarker studies and in the longer term by collaborating with modellers and fishery biologists.

Pilot survey of NICU nurses' interest in the neonatal nurse practitioner role.

PubMed

Rasmussen, Lynn B; Vargo, Lyn E; Reavey, Daphne A; Hunter, Kim S

2005-02-01

This descriptive, qualitative pilot study explored the interest and perceptions of neonatal intensive care unit (NICU) nurses regarding the neonatal nurse practitioner (NNP) role. Motivating factors to become an NNP, challenges facing NNPs, and rewards of the NNP role from the perspectives of NICU nurses were explored. The convenience sample was obtained using 2 survey techniques. The first sample group included nurses who were employed in Level III NICUs located within 2 major Midwestern cities. In order to confirm the data and to expand the scope, the second sample group was recruited from NICU nurses who were attending a regional educational conference. All participants were currently employed NICU nurses and were therefore potential NNP students. Combining the participants of both enrollment techniques resulted in a potential of 696 subjects. A simple self-administered survey was used to collect data. Narrative data were qualitatively analyzed. Demographic data and categorical items were quantified. This study achieved a total 30% response rate (n = 209). Of the total participants, only 32% of Level III NICU nurses were interested in becoming an NNP. Analysis of the data revealed 6 major categories (themes) of reasons why nurses were not interested in the NNP role. The themes most often mentioned by the participants were (1) obligations to family and/or work (46%) and (2) too much responsibility in the NNP role (30%). The data also revealed several different rewards and challenges for those in the NNP role as well as factors that may motivate nurses to become an NNP. Given the current NNP shortage, an increase in the supply of NNPs for the workforce is imperative. Current enrollment in NNP academic programs does not appear to be meeting the demand. Exploring the factors that influence enrollment in NNP programs from the perspective of potential NNP students is the first step towards increasing the supply of NNPs. The majority of participants were not interested in becoming an NNP for a variety of reasons. Negative perceptions of the NNP role were identified. Solutions posed from these results may provide scientifically sound solutions to help ease the shortage of NNPs. The findings of this naturalistic inquiry may be used to develop an instrument to measure interest in the NNP role.

A difficult Arctic science issue: Midlatitude weather linkages

NASA Astrophysics Data System (ADS)

Overland, James E.

2016-09-01

There is at present unresolved uncertainty whether Arctic amplification (increased air temperatures and loss of sea ice) impacts the location and intensities of recent major weather events in midlatitudes. There are three major impediments. The first is the null hypothesis where the shortness of time series since major amplification (∼15 years) is dominated by the variance of the physical process in the attribution calculation. This makes it impossible to robustly distinguish the influence of Arctic forcing of regional circulation from random events. The second is the large chaotic jet stream variability at midlatitudes producing a small Arctic forcing signal-to-noise ratio. Third, there are other potential external forcings of hemispheric circulation, such as teleconnections driven by tropical and midlatitude sea surface temperature anomalies. It is, however, important to note and understand recent emerging case studies. There is evidence for a causal connection of Barents-Kara sea ice loss, a stronger Siberian High, and cold air outbreaks into eastern Asia. Recent cold air penetrating into the southeastern United States was related to a shift in the long-wave atmospheric wind pattern and reinforced by warmer temperatures west of Greenland. Arctic Linkages is a major research challenge that benefits from an international focus on the topic.

3D Printing of Lotus Root-Like Biomimetic Materials for Cell Delivery and Tissue Regeneration.

PubMed

Feng, Chun; Zhang, Wenjie; Deng, Cuijun; Li, Guanglong; Chang, Jiang; Zhang, Zhiyuan; Jiang, Xinquan; Wu, Chengtie

2017-12-01

Biomimetic materials have drawn more and more attention in recent years. Regeneration of large bone defects is still a major clinical challenge. In addition, vascularization plays an important role in the process of large bone regeneration and microchannel structure can induce endothelial cells to form rudimentary vasculature. In recent years, 3D printing scaffolds are major materials for large bone defect repair. However, these traditional 3D scaffolds have low porosity and nonchannel structure, which impede angiogenesis and osteogenesis. In this study, inspired by the microstructure of natural plant lotus root, biomimetic materials with lotus root-like structures are successfully prepared via a modified 3D printing strategy. Compared with traditional 3D materials, these biomimetic materials can significantly improve in vitro cell attachment and proliferation as well as promote in vivo osteogenesis, indicating potential application for cell delivery and bone regeneration.

Integrated bioleaching of copper metal from waste printed circuit board-a comprehensive review of approaches and challenges.

PubMed

Awasthi, Abhishek Kumar; Zeng, Xianlai; Li, Jinhui

2016-11-01

Waste electrical and electronic equipment (e-waste) is the most rapidly growing waste stream in the world, and the majority of the residues are openly disposed of in developing countries. Waste printed circuit boards (WPCBs) make up the major portion of e-waste, and their informal recycling can cause environmental pollution and health risks. Furthermore, the conventional disposal and recycling techniques-mechanical treatments used to recover valuable metals, including copper-are not sustainable in the long term. Chemical leaching is rapid and efficient but causes secondary pollution. Bioleaching is a promising approach, eco-friendly and economically feasible, but it is slower process. This review considers the recycling potential of microbes and suggests an integrated bioleaching approach for Cu extraction and recovery from WPCBs. The proposed recycling system should be more effective, efficient and both technically and economically feasible.

Communicating Risks and Benefits in Informed Consent for Research: A Qualitative Study

PubMed Central

Nusbaum, Lika; Douglas, Brenda; Damus, Karla; Paasche-Orlow, Michael; Estrella-Luna, Neenah

2017-01-01

Multiple studies have documented major limitations in the informed consent process for the recruitment of clinical research participants. One challenging aspect of this process is successful communication of risks and benefits to potential research participants. This study explored the opinions and attitudes of informed consent experts about conveying risks and benefits to inform the development of a survey about the perspectives of research nurses who are responsible for obtaining informed consent for clinical trials. The major themes identified were strategies for risks and benefits communication, ensuring comprehension, and preparation for the role of the consent administrator. From the experts’ perspective, inadequate education and training of the research staff responsible for informed consent process contribute to deficiencies in the informed consent process and risks and benefits communication. Inconsistencies in experts’ opinions and critique of certain widely used communication practices require further consideration and additional research. PMID:28975139

3D Printing of Lotus Root‐Like Biomimetic Materials for Cell Delivery and Tissue Regeneration

PubMed Central

Feng, Chun; Zhang, Wenjie; Deng, Cuijun; Li, Guanglong; Chang, Jiang; Zhang, Zhiyuan

2017-01-01

Abstract Biomimetic materials have drawn more and more attention in recent years. Regeneration of large bone defects is still a major clinical challenge. In addition, vascularization plays an important role in the process of large bone regeneration and microchannel structure can induce endothelial cells to form rudimentary vasculature. In recent years, 3D printing scaffolds are major materials for large bone defect repair. However, these traditional 3D scaffolds have low porosity and nonchannel structure, which impede angiogenesis and osteogenesis. In this study, inspired by the microstructure of natural plant lotus root, biomimetic materials with lotus root‐like structures are successfully prepared via a modified 3D printing strategy. Compared with traditional 3D materials, these biomimetic materials can significantly improve in vitro cell attachment and proliferation as well as promote in vivo osteogenesis, indicating potential application for cell delivery and bone regeneration. PMID:29270348

Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis

PubMed Central

Aikawa, Elena; Newby, David E.; Tarkin, Jason M.; Rudd, James H.F.; Narula, Jagat; Fayad, Zahi A.

2016-01-01

Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques. PMID:27390335

Metabolic and Homeostatic Changes in Seizures and Acquired Epilepsy—Mitochondria, Calcium Dynamics and Reactive Oxygen Species

PubMed Central

Kovac, Stjepana; Dinkova Kostova, Albena T.; Melzer, Nico; Meuth, Sven G.; Gorji, Ali

2017-01-01

Acquired epilepsies can arise as a consequence of brain injury and result in unprovoked seizures that emerge after a latent period of epileptogenesis. These epilepsies pose a major challenge to clinicians as they are present in the majority of patients seen in a common outpatient epilepsy clinic and are prone to pharmacoresistance, highlighting an unmet need for new treatment strategies. Metabolic and homeostatic changes are closely linked to seizures and epilepsy, although, surprisingly, no potential treatment targets to date have been translated into clinical practice. We summarize here the current knowledge about metabolic and homeostatic changes in seizures and acquired epilepsy, maintaining a particular focus on mitochondria, calcium dynamics, reactive oxygen species and key regulators of cellular metabolism such as the Nrf2 pathway. Finally, we highlight research gaps that will need to be addressed in the future which may help to translate these findings into clinical practice. PMID:28885567

Exploiting virus-like particles as innovative vaccines against emerging viral infections.

PubMed

Jeong, Hotcherl; Seong, Baik Lin

2017-03-01

Emerging viruses pose a major threat to humans and livestock with global public health and economic burdens. Vaccination remains an effective tool to reduce this threat, and yet, the conventional cell culture often fails to produce sufficient vaccine dose. As an alternative to cell-culture based vaccine, virus-like particles (VLPs) are considered as a highpriority vaccine strategy against emerging viruses. VLPs represent highly ordered repetitive structures via macromolecular assemblies of viral proteins. The particulate nature allows efficient uptake into antigen presenting cells stimulating both innate and adaptive immune responses towards enhanced vaccine efficacy. Increasing research activity and translation opportunity necessitate the advances in the design of VLPs and new bioprocessing modalities for efficient and cost-effective production. Herein, we describe major achievements and challenges in this endeavor, with respect to designing strategies to harnessing the immunogenic potential, production platforms, downstream processes, and some exemplary cases in developing VLP-based vaccines.

A Flexible Hierarchical Bayesian Modeling Technique for Risk Analysis of Major Accidents.

PubMed

Yu, Hongyang; Khan, Faisal; Veitch, Brian

2017-09-01

Safety analysis of rare events with potentially catastrophic consequences is challenged by data scarcity and uncertainty. Traditional causation-based approaches, such as fault tree and event tree (used to model rare event), suffer from a number of weaknesses. These include the static structure of the event causation, lack of event occurrence data, and need for reliable prior information. In this study, a new hierarchical Bayesian modeling based technique is proposed to overcome these drawbacks. The proposed technique can be used as a flexible technique for risk analysis of major accidents. It enables both forward and backward analysis in quantitative reasoning and the treatment of interdependence among the model parameters. Source-to-source variability in data sources is also taken into account through a robust probabilistic safety analysis. The applicability of the proposed technique has been demonstrated through a case study in marine and offshore industry. © 2017 Society for Risk Analysis.

Status of floriculture in Europe.

PubMed

Van Huylenbroeck, Johan

2010-01-01

Europe is traditionally the largest producer of floricultural products in the world with an estimated production value of over 12 billion euro in 2006. The Netherlands, Italy, Germany, Spain, United Kingdom and France are the main centres of production. More recently, a significant growth in production area was observed in Poland also. The Dutch auctions remain the world's largest trading system for flowers and plants. Looking at the intra-European trade, Belgium and Denmark are also major exporting countries. The consumption of floricultural products increased strongly within Europe during the last years. Especially, Eastern Europe has a big potential as a new market. In these countries, the demand for ornamentals will increase due to the rise of income and the level of prosperity. In spite of the positive developments in consumption and production, increasing energy costs, growing environmental concern and globalisation of production, trade and markets will form the major challenges European floricultural industry has to deal with in the near future.

Built to Last: Curricular Planning to Stand the Test of Time

NASA Astrophysics Data System (ADS)

Clark, J. J.; Knudsen, A.; Bjornerud, M.

2007-12-01

At Lawrence University rapid, wholesale personnel changes allowed us the unique opportunity to completely rethink our curriculum in 2000. The major challenge that we faced was how to offer a curriculum that reflects the growing interdisciplinarity and complexity of the geosciences with a relatively small faculty (three members). We addressed this issue by identifying the essential elements of a geoscience program and reconciled these with our own priorities, strengths, potentials, and limitations. We then built the strongest possible program given these resources and constraints. As new faculty members were hired, we deliberately sought out versatile, flexible candidates whose training embraced several sub-disciplines. As we discussed the skills and concepts we considered essential for geology students and assessed the expertise of our faculty, we concluded that for us the most efficient curricular framework would emphasize 1) fundamental processes that drive Earth systems and 2) connections with cognate sciences. This shift in focus also has allowed us to serve the interdisciplinary Environmental studies curriculum in an integral way, without undercutting the department's own mission. There are serious challenges to departments looking to change their core curriculum. Resistance to change can come from both within departments and through external entities. Because all of our faculty were new to Lawrence, we faced no internal resistance. However, we have faced some challenges in explaining our major to "old school" alumni, emeriti, and to some graduate programs who note the lack of specific course titles on student transcripts. We also have found the need to make adjustments to our initial curricular redesign to effectively cover topics such as optical mineralogy and sedimentology and stratigraphy. Finding appropriate textbooks for our courses continues to pose a problem. Despite these challenges, we are very positive about the student response to our changes. Enrollments in our courses are up almost 20% and we see an increasing number of students from other sciences in our upper level classes. Although the number of majors has not changed significantly, we have noticed that more of our majors are attending graduate school or finding employment in the geosciences. As the scope of the geosciences grows and the boundaries between disciplines blurs, there is no longer any possibility of `comprehensive coverage' in the undergraduate curriculum. We do not consider our curriculum a universally applicable template. But we do believe that leading geoscience programs of the future will emerge from departments that identify their priorities, know their strengths, and construct their curricula based upon these intellectual foundations.

The Grand Ethiopian Renaissance Dam: Source of cooperation or contention?

USGS Publications Warehouse

Teferi Taye, Meron; Tadesse, Tsegaye; Senay, Gabriel; Block, Paul

2016-01-01

This paper discusses the challenges and benefits of the Grand Ethiopian Renaissance Dam (GERD), which is under construction and expected to be operational on the Blue Nile River in Ethiopia in a few years. Like many large-scale projects on transboundary rivers, the GERD has been criticized for potentially jeopardizing downstream water security and livelihoods through upstream unilateral decision making. In spite of the contentious nature of the project, the authors argue that this project can provide substantial benefits for regional development. The GERD, like any major river infrastructure project, will undeniably bring about social, environmental, and economic change, and in this unique case has, on balance, the potential to achieve success on all fronts. It must be stressed, however, that strong partnerships between riparian countries are essential. National success is contingent on regional cooperation.

Food sovereignty: an alternative paradigm for poverty reduction and biodiversity conservation in Latin America.

PubMed

Chappell, M Jahi; Wittman, Hannah; Bacon, Christopher M; Ferguson, Bruce G; Barrios, Luis García; Barrios, Raúl García; Jaffee, Daniel; Lima, Jefferson; Méndez, V Ernesto; Morales, Helda; Soto-Pinto, Lorena; Vandermeer, John; Perfecto, Ivette

2013-01-01

Strong feedback between global biodiversity loss and persistent, extreme rural poverty are major challenges in the face of concurrent food, energy, and environmental crises. This paper examines the role of industrial agricultural intensification and market integration as exogenous socio-ecological drivers of biodiversity loss and poverty traps in Latin America. We then analyze the potential of a food sovereignty framework, based on protecting the viability of a diverse agroecological matrix while supporting rural livelihoods and global food production. We review several successful examples of this approach, including ecological land reform in Brazil, agroforestry, milpa, and the uses of wild varieties in smallholder systems in Mexico and Central America. We highlight emergent research directions that will be necessary to assess the potential of the food sovereignty model to promote both biodiversity conservation and poverty reduction.

Climate change and malaria in Canada: a systems approach.

PubMed

Berrang-Ford, L; Maclean, J D; Gyorkos, Theresa W; Ford, J D; Ogden, N H

2009-01-01

This article examines the potential for changes in imported and autochthonous malaria incidence in Canada as a consequence of climate change. Drawing on a systems framework, we qualitatively characterize and assess the potential direct and indirect impact of climate change on malaria in Canada within the context of other concurrent ecological and social trends. Competent malaria vectors currently exist in southern Canada, including within this range several major urban centres, and conditions here have historically supported endemic malaria transmission. Climate change will increase the occurrence of temperature conditions suitable for malaria transmission in Canada, which, combined with trends in international travel, immigration, drug resistance, and inexperience in both clinical and laboratory diagnosis, may increase malaria incidence in Canada and permit sporadic autochthonous cases. This conclusion challenges the general assumption of negligible malaria risk in Canada with climate change.

Selective control of electron and hole tunneling in 2D assembly

PubMed Central

Chu, Dongil; Lee, Young Hee; Kim, Eun Kyu

2017-01-01

Recent discoveries in the field of two-dimensional (2D) materials have led to the demonstration of exotic devices. Although they have new potential applications in electronics, thermally activated transport over a metal/semiconductor barrier sets physical subthermionic limitations. The challenge of realizing an innovative transistor geometry that exploits this concern remains. A new class of 2D assembly (namely, “carristor”) with a configuration similar to the metal-insulator-semiconductor structure is introduced in this work. Superior functionalities, such as a current rectification ratio of up to 400,000 and a switching ratio of higher than 106 at room temperature, are realized by quantum-mechanical tunneling of majority and minority carriers across the barrier. These carristors have a potential application as the fundamental building block of low–power consumption electronics. PMID:28439554

Climate Change and Malaria in Canada: A Systems Approach

PubMed Central

Berrang-Ford, L.; MacLean, J. D.; Gyorkos, Theresa W.; Ford, J. D.; Ogden, N. H.

2009-01-01

This article examines the potential for changes in imported and autochthonous malaria incidence in Canada as a consequence of climate change. Drawing on a systems framework, we qualitatively characterize and assess the potential direct and indirect impact of climate change on malaria in Canada within the context of other concurrent ecological and social trends. Competent malaria vectors currently exist in southern Canada, including within this range several major urban centres, and conditions here have historically supported endemic malaria transmission. Climate change will increase the occurrence of temperature conditions suitable for malaria transmission in Canada, which, combined with trends in international travel, immigration, drug resistance, and inexperience in both clinical and laboratory diagnosis, may increase malaria incidence in Canada and permit sporadic autochthonous cases. This conclusion challenges the general assumption of negligible malaria risk in Canada with climate change. PMID:19277107

Dielectrophoresis for Biomedical Sciences Applications: A Review

PubMed Central

Abd Rahman, Nurhaslina; Ibrahim, Fatimah; Yafouz, Bashar

2017-01-01

Dielectrophoresis (DEP) is a label-free, accurate, fast, low-cost diagnostic technique that uses the principles of polarization and the motion of bioparticles in applied electric fields. This technique has been proven to be beneficial in various fields, including environmental research, polymer research, biosensors, microfluidics, medicine and diagnostics. Biomedical science research is one of the major research areas that could potentially benefit from DEP technology for diverse applications. Nevertheless, many medical science research investigations have yet to benefit from the possibilities offered by DEP. This paper critically reviews the fundamentals, recent progress, current challenges, future directions and potential applications of research investigations in the medical sciences utilizing DEP technique. This review will also act as a guide and reference for medical researchers and scientists to explore and utilize the DEP technique in their research fields. PMID:28245552

Alternative Cell Sources to Adult Hepatocytes for Hepatic Cell Therapy.

PubMed

Pareja, Eugenia; Gómez-Lechón, María José; Tolosa, Laia

2017-01-01

Adult hepatocyte transplantation is limited by scarce availability of suitable donor liver tissue for hepatocyte isolation. New cell-based therapies are being developed to supplement whole-organ liver transplantation, to reduce the waiting-list mortality rate, and to obtain more sustained and significant metabolic correction. Fetal livers and unsuitable neonatal livers for organ transplantation have been proposed as potential useful sources of hepatic cells for cell therapy. However, the major challenge is to use alternative cell sources for transplantation that can be derived from reproducible methods. Different types of stem cells with hepatic differentiation potential are eligible for generating large numbers of functional hepatocytes for liver cell therapy to treat degenerative disorders, inborn hepatic metabolic diseases, and organ failure. Clinical trials are designed to fully establish the safety profile of such therapies and to define target patient groups and standardized protocols.