Sample records for considerable challenges remain

  1. Social media and pharmacovigilance: A review of the opportunities and challenges

    PubMed Central

    Sloane, Richard; Osanlou, Orod; Lewis, David; Bollegala, Danushka; Maskell, Simon; Pirmohamed, Munir

    2015-01-01

    Adverse drug reactions come at a considerable cost on society. Social media are a potentially invaluable reservoir of information for pharmacovigilance, yet their true value remains to be fully understood. In order to realize the benefits social media holds, a number of technical, regulatory and ethical challenges remain to be addressed. We outline these key challenges identifying relevant current research and present possible solutions. PMID:26147850

  2. Social media and pharmacovigilance: A review of the opportunities and challenges.

    PubMed

    Sloane, Richard; Osanlou, Orod; Lewis, David; Bollegala, Danushka; Maskell, Simon; Pirmohamed, Munir

    2015-10-01

    Adverse drug reactions come at a considerable cost on society. Social media are a potentially invaluable reservoir of information for pharmacovigilance, yet their true value remains to be fully understood. In order to realize the benefits social media holds, a number of technical, regulatory and ethical challenges remain to be addressed. We outline these key challenges identifying relevant current research and present possible solutions. © 2015 The British Pharmacological Society.

  3. Multicultural and Diversity Considerations in the New "Code of Professional Ethics for Rehabilitation Counselors"

    ERIC Educational Resources Information Center

    Cartwright, Brenda Y.; Fleming, Christine L.

    2010-01-01

    As the demographic transformation of the U.S. population continues, the challenges of multicultural and diversity-based considerations remain a central focus, as does the need to incorporate cultural competencies into the practice of rehabilitation. The Commission on Rehabilitation Counselor Certification's 2010 "Code of Professional Ethics for…

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

    ERIC Educational Resources Information Center

    Gopinathan, S.

    2006-01-01

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

  5. Leading Educational Change and Improvement at Scale: Some Inconvenient Truths about System Performance

    ERIC Educational Resources Information Center

    Harris, Alma; Jones, Michelle

    2017-01-01

    The challenges of securing educational change and transformation, at scale, remain considerable. While sustained progress has been made in some education systems (Fullan, 2009; Hargreaves & Shirley, 2009) generally, it remains the case that the pathway to large-scale, system improvement is far from easy or straightforward. While large-scale…

  6. Establishing a Methodology to Examine the Effects of War-Zone PTSD on the Family: The Family Foundations Study

    PubMed Central

    Vasterling, Jennifer J.; Taft, Casey T.; Proctor, Susan P.; MacDonald, Helen Z.; Lawrence, Amy; Kalill, Kathleen; Kaiser, Anica P.; Lee, Lewina O.; King, Daniel W.; King, Lynda A.; Fairbank, John A.

    2015-01-01

    Military deployment may adversely affect not only returning veterans, but their families, as well. As a result, researchers have increasingly focused on identifying risk and protective factors for successful family adaptation to war-zone deployment, re-integration of the returning veteran, and the longer-term psychosocial consequences of deployment experienced by some veterans and families. Posttraumatic stress disorder (PTSD) among returning veterans may pose particular challenges to military and military veteran families; however, questions remain regarding the impact of the course of veteran PTSD and other potential moderating factors on family adaptation to military deployment. The Family Foundations Study builds upon an established longitudinal cohort of Army soldiers (i.e., the Neurocognition Deployment Health Study) to help address remaining knowledge gaps. This report describes the conceptual framework and key gaps in knowledge that guided the study design, methodological challenges and special considerations in conducting military family research, and how these gaps, challenges, and special considerations are addressed by the study. PMID:26077194

  7. Ready-to-use foods for management of moderate acute malnutrition: Considerations for scaling up production and use in programs

    USDA-ARS?s Scientific Manuscript database

    Ready-to-use foods are one of the available strategies for the treatment of moderate acute malnutrition (MAM), but challenges remain in the use of these products in programs at scale. This paper focuses on two challenges: the need for cheaper formulations using locally available ingredients that are...

  8. Policies to Support Wind Power Deployment: Key Considerations and Good Practices

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

    Cox, Sadie; Tegen, Suzanne; Baring-Gould, Ian

    2015-05-19

    Policies have played an important role in scaling up wind deployment and increasing its economic viability while also supporting country-specific economic, social, and environmental development goals. Although wind power has become cost-competitive in several contexts, challenges to wind power deployment remain. Within the context of country-specific goals and challenges, policymakers are seeking

  9. Large eddy simulation applications in gas turbines.

    PubMed

    Menzies, Kevin

    2009-07-28

    The gas turbine presents significant challenges to any computational fluid dynamics techniques. The combination of a wide range of flow phenomena with complex geometry is difficult to model in the context of Reynolds-averaged Navier-Stokes (RANS) solvers. We review the potential for large eddy simulation (LES) in modelling the flow in the different components of the gas turbine during a practical engineering design cycle. We show that while LES has demonstrated considerable promise for reliable prediction of many flows in the engine that are difficult for RANS it is not a panacea and considerable application challenges remain. However, for many flows, especially those dominated by shear layer mixing such as in combustion chambers and exhausts, LES has demonstrated a clear superiority over RANS for moderately complex geometries although at significantly higher cost which will remain an issue in making the calculations relevant within the design cycle.

  10. Challenges and considerations for the design and production of a purpose-optimized body-worn wrist-watch computer

    NASA Astrophysics Data System (ADS)

    Narayanaswami, Chandra; Raghunath, Mandayam T.

    2004-09-01

    We outline a collection of technological challenges in the design of wearable computers with a focus on one of the most desirable form-factors, the wrist watch. We describe our experience with building three generations of wrist watch computers. We built these research prototypes as platforms to investigate the fundamental limitations of wearable computing. Results of our investigations are presented in the form of challenges that have been overcome and those that still remain.

  11. Sow lying behaviors before, during and after farrowing

    USDA-ARS?s Scientific Manuscript database

    Piglet pre-weaning mortality remains a considerable challenge for the swine industry, representing one of the key areas where animal well-being and economical interest coincide. Sows and piglets carry out a complex series of behaviors during the farrowing/lactation period. These behaviors during the...

  12. Planning as an Iterative Process

    NASA Technical Reports Server (NTRS)

    Smith, David E.

    2012-01-01

    Activity planning for missions such as the Mars Exploration Rover mission presents many technical challenges, including oversubscription, consideration of time, concurrency, resources, preferences, and uncertainty. These challenges have all been addressed by the research community to varying degrees, but significant technical hurdles still remain. In addition, the integration of these capabilities into a single planning engine remains largely unaddressed. However, I argue that there is a deeper set of issues that needs to be considered namely the integration of planning into an iterative process that begins before the goals, objectives, and preferences are fully defined. This introduces a number of technical challenges for planning, including the ability to more naturally specify and utilize constraints on the planning process, the ability to generate multiple qualitatively different plans, and the ability to provide deep explanation of plans.

  13. HPT and Business Process Management

    ERIC Educational Resources Information Center

    Edgar, Robert

    2004-01-01

    A relatively new feature of human performance technology (HPT) is e-training, which, while considerably more economical and time-efficient than traveling to a remote location for training, presents other challenges. Course length remains a problem, and there are professional organizations for which performance improvement is too difficult to…

  14. Supersonic Post-Combustion Inertial CO 2 Extraction System Final Report

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

    Balepin, Vladimir

    This report summarizes the effort carried out under NETL contract DE- FE0013122 from 1 October 2013 to 31 March 2017. As described in this document, technical challenges realized during the performance of this project resulted in completion of only the first two of three planned budget periods. Despite this outcome, substantial progress was made toward understanding and maturing the CO 2 capture technology under consideration and considerable future promise remains for applications requiring lower CO 2 capture and/or lower CO 2.

  15. Invasion complexity at large spatial scales is an emergent property of interactions among landscape characteristics and invader traits

    USDA-ARS?s Scientific Manuscript database

    Understanding the potential for invasive spread is an important consideration for novel agricultural species that may be translocated or introduced into new regions. However, estimating invasion risks remains a challenging problem, particularly in the context of real, complex landscapes. There is ...

  16. Creating Shared Norms in Schools--A Theoretical Approach

    ERIC Educational Resources Information Center

    Macdonald, Maryanne; Gringart, Eyal; Gray, Jan

    2016-01-01

    Whilst some improvements to Indigenous education outcomes have occurred in recent years, there remains considerable inequity in the educational experiences and long-term engagement of Indigenous and non-Indigenous students. One of the factors contributing to the challenging environment for Indigenous students is dissonance of social norms, as a…

  17. Hydrologic influences on stream temperatures for Little Creek and Scotts Creek, Santa Cruz County, California

    Treesearch

    Justin M. Louen; Christopher G. Surfleet

    2017-01-01

    Stream temperature impacts have resulted in increased restrictions on land management, such as timber harvest and riparian restoration, creating considerable uncertainty for future planning and management of redwood (Sequoia sempervirens (D.Don) Endl.) forestlands. Challenges remain in the assessment of downstream cumulative stream...

  18. Retention and Professional Mentoring of Beginning Career and Technical Education Teachers

    ERIC Educational Resources Information Center

    Mordan, Benjamin R.

    2012-01-01

    A fundamental requirement for providing quality education in schools is to encourage highly qualified individuals with the necessary knowledge and skill to enter the teaching profession and remain employed in this occupation. Attracting and retaining effective teachers has historically presented a considerable challenge for schools across many…

  19. Development and assessment of plant-based synthetic odor baits for surveillance and control of Malaria vectors

    USDA-ARS?s Scientific Manuscript database

    Recent malaria vector control measures have considerably reduced indoor biting mosquito populations. However, reducing the outdoor biting populations remains a challenge because of the unavailability of appropriate lures to achieve this. This study sought to test the efficacy of plant-based syntheti...

  20. Integrating Theory and Empirical Science in School Psychology: Progress and Remaining Challenges

    ERIC Educational Resources Information Center

    Hughes, Jan N.

    2015-01-01

    This article reviews progress made since Hughes (2000a) criticized intervention research in school psychology for insufficient consideration of theory. A review of contemporary intervention research published in journals specifically identified with the specialty of school psychology supports the conclusion that current school psychology…

  1. Cognitive Adaptation to the Experience of Social and Cultural Diversity

    ERIC Educational Resources Information Center

    Crisp, Richard J.; Turner, Rhiannon N.

    2011-01-01

    Diversity is a defining characteristic of modern society, yet there remains considerable debate over the benefits that it brings. The authors argue that positive psychological and behavioral outcomes will be observed only when social and cultural diversity is experienced in a way that challenges stereotypical expectations and that when this…

  2. Advancing High-Quality Preschool Inclusion: A Discussion and Recommendations for the Field

    ERIC Educational Resources Information Center

    Barton, Erin E.; Smith, Barbara J.

    2015-01-01

    Although considerable progress has been achieved regarding the research and laws supporting preschool inclusion, access to inclusive preschool environments remains intangible for many children with disabilities in the United States. The purpose of this article is to discuss current challenges and solutions to high-quality preschool inclusion. We…

  3. Concerns, Considerations, and New Ideas for Data Collection and Research in Educational Technology Studies

    ERIC Educational Resources Information Center

    Bebell, Damian; O'Dwyer, Laura M.; Russell, Michael; Hoffmann, Tom

    2010-01-01

    In the following pages, we examine some common methodological challenges in educational technology research and highlight new data collection approaches using examples from the literature and our own work. Given that surveys and questionnaires remain widespread and dominant tools across nearly all studies of educational technology, we first…

  4. The difficult legacy of Turing's wager.

    PubMed

    Thwaites, Andrew; Soltan, Andrew; Wieser, Eric; Nimmo-Smith, Ian

    2017-08-01

    Describing the human brain in mathematical terms is an important ambition of neuroscience research, yet the challenges remain considerable. It was Alan Turing, writing in 1950, who first sought to demonstrate how time-consuming such an undertaking would be. Through analogy to the computer program, Turing argued that arriving at a complete mathematical description of the mind would take well over a thousand years. In this opinion piece, we argue that - despite seventy years of progress in the field - his arguments remain both prescient and persuasive.

  5. Engaging Students in Physical Education: Key Challenges and Opportunities for Physical Educators in Urban Settings

    ERIC Educational Resources Information Center

    Sliwa, Sarah; Nihiser, Allison; Lee, Sarah; McCaughtry, Nathan; Culp, Brian; Michael, Shannon

    2017-01-01

    In October 2009, "JOPERD" published a special issue about "Engaging Urban Youths in Physical Education and Physical Activity." Seven years later, many of the considerations mentioned remain relevant, such as large class sizes, limited access to equipment, and the lack of a dedicated gymnasium or outdoor space. These structural…

  6. Gender Risks and Education: The Particular Classroom Challenges for Urban Low-Income African American Boys

    ERIC Educational Resources Information Center

    Thomas, Duane E.; Stevenson, Howard

    2009-01-01

    A fundamental consideration in discourses on risk and schooling for primary and secondary school-age students focuses on gender inequalities in the classroom. Gender equity in education debates have raged for several decades and so remain an enduring concern of educators and researchers across the nation. However, educational research often…

  7. New Considerations in the Prevention of Aversives, Restraint, and Seclusion: Incorporating the Role of Relationships into an Ecological Perspective

    ERIC Educational Resources Information Center

    Amos, Patricia A.

    2004-01-01

    While many individuals with challenging behaviors now enjoy the benefits of inclusion and self-determination, large numbers of their peers remain in segregated, restrictive settings and continue to be subjected to coercive intervention plans that include aversives, (nonemergency) restraint, and seclusion as "treatment." A rising tide of…

  8. Orthostatic hypotension: epidemiology, pathophysiology and management

    NASA Technical Reports Server (NTRS)

    Jacob, G.; Robertson, D.

    1995-01-01

    Orthostatic hypotension is characterized by low upright blood pressure levels and symptoms of cerebral hypoperfusion. Whereas orthostatic hypotension is heterogeneous, correct pathophysiologic diagnosis is important because of therapeutic and prognostic considerations. Although therapy is not usually curative, it can be extraordinarily beneficial if it is individually tailored. Management of the Shy-Drager syndrome (multiple-system atrophy) remains a formidable challenge.

  9. Astrophysics and Cosmology: International Partnerships

    NASA Astrophysics Data System (ADS)

    Blandford, Roger

    2016-03-01

    Most large projects in astrophysics and cosmology are international. This raises many challenges including: --Aligning the sequence of: proposal, planning, selection, funding, construction, deployment, operation, data mining in different countries --Managing to minimize cost growth through reconciling different practices --Communicating at all levels to ensure a successful outcome --Stabilizing long term career opportunities. There has been considerable progress in confronting these challenges. Lessons learned from past collaborations are influencing current facilities but much remains to be done if we are to optimize the scientific and public return on the expenditure of financial and human resources.

  10. Considerations for Community-Based mHealth Initiatives: Insights From Three Beacon Communities

    PubMed Central

    2013-01-01

    Mobile health (mHealth) is gaining widespread attention for its potential to engage patients in their health and health care in their daily lives. Emerging evidence suggests that mHealth interventions can be used effectively to support behavior change, but numerous challenges remain when implementing these programs at the community level. This paper provides an overview of considerations when implementing community-based mHealth initiatives, based on the experiences of three Beacon Communities across the United States that have launched text messaging (short message service, SMS) pilot programs aimed at diabetes risk reduction and disease management. The paper addresses lessons learned and suggests strategies to overcome challenges related to developing text message content, conducting marketing and outreach, enrolling participants, engaging providers, evaluating program effectiveness, and sustaining and scaling the programs. PMID:24128406

  11. The 5th Canadian Symposium on Hepatitis C Virus: We Are Not Done Yet—Remaining Challenges in Hepatitis C

    PubMed Central

    van Buuren, Nicholas; Fradette, Lorraine; Grebely, Jason; King, Alexandra; Krajden, Mel; MacParland, Sonya A.; Marshall, Alison; Saeed, Sahar; Wilson, Joyce; Klein, Marina B.

    2016-01-01

    Hepatitis C virus (HCV) affects approximately 268,000 Canadians and results in more years of life lost than any other infectious disease in the country. Both the Canadian Institutes of Health Research (CIHR) and the Public Health Agency of Canada (PHAC) have identified HCV-related liver disease as a priority and supported the establishment of a National Hepatitis C Research Network. In 2015, the introduction of new interferon- (IFN-) free therapies with high cure rates (>90%) and few side effects revolutionized HCV therapy. However, a considerable proportion of the population remains undiagnosed and treatment uptake remains low in Canada due to financial, geographical, cultural, and social barriers. Comprehensive prevention strategies, including enhanced harm reduction, broader screening, widespread treatment, and vaccine development, are far from being realized. The theme of the 2016 symposium, “We're not done yet: remaining challenges in Hepatitis C,” was focused on identifying strategies to enhance prevention, diagnosis, and treatment of HCV to reduce disease burden and ultimately eliminate HCV in Canada. PMID:27843889

  12. Structural and mechanical design challenges of space shuttle solid rocket boosters separation and recovery subsystems

    NASA Technical Reports Server (NTRS)

    Woodis, W. R.; Runkle, R. E.

    1985-01-01

    The design of the space shuttle solid rocket booster (SRB) subsystems for reuse posed some unique and challenging design considerations. The separation of the SRBs from the cluster (orbiter and external tank) at 150,000 ft when the orbiter engines are running at full thrust meant the two SRBs had to have positive separation forces pushing them away. At the same instant, the large attachments that had reacted launch loads of 7.5 million pounds thrust had to be servered. These design considerations dictated the design requirements for the pyrotechnics and separation rocket motors. The recovery and reuse of the two SRBs meant they had to be safely lowered to the ocean, remain afloat, and be owed back to shore. In general, both the pyrotechnic and recovery subsystems have met or exceeded design requirements. In twelve vehicles, there has only been one instance where the pyrotechnic system has failed to function properly.

  13. Progress and challenges of disaster health management in China: a scoping review.

    PubMed

    Zhong, Shuang; Clark, Michele; Hou, Xiang-Yu; Zang, Yuli; FitzGerald, Gerard

    2014-01-01

    Despite the importance of an effective health system response to various disasters, relevant research is still in its infancy, especially in middle- and low-income countries. This paper provides an overview of the status of disaster health management in China, with its aim to promote the effectiveness of the health response for reducing disaster-related mortality and morbidity. A scoping review method was used to address the recent progress of and challenges to disaster health management in China. Major health electronic databases were searched to identify English and Chinese literature that were relevant to the research aims. The review found that since 2003 considerable progress has been achieved in the health disaster response system in China. However, there remain challenges that hinder effective health disaster responses, including low standards of disaster-resistant infrastructure safety, the lack of specific disaster plans, poor emergency coordination between hospitals, lack of portable diagnostic equipment and underdeveloped triage skills, surge capacity, and psychological interventions. Additional challenges include the fragmentation of the emergency health service system, a lack of specific legislation for emergencies, disparities in the distribution of funding, and inadequate cost-effective considerations for disaster rescue. One solution identified to address these challenges appears to be through corresponding policy strategies at multiple levels (e.g. community, hospital, and healthcare system level).

  14. Perspectives on biological growth and remodeling

    PubMed Central

    Ambrosi, D.; Ateshian, G. A.; Arruda, E. M.; Cowin, S. C.; Dumais, J.; Goriely, A.; Holzapfel, G. A.; Humphrey, J. D.; Kemkemer, R.; Kuhl, E.; Olberding, J. E.; Taber, L. A.; Garikipati, K.

    2011-01-01

    The continuum mechanical treatment of biological growth and remodeling has attracted considerable attention over the past fifteen years. Many aspects of these problems are now well-understood, yet there remain areas in need of significant development from the standpoint of experiments, theory, and computation. In this perspective paper we review the state of the field and highlight open questions, challenges, and avenues for further development. PMID:21532929

  15. From Policy to Practice: The Challenges of Providing High Quality Physical Education and School Sport Faced by Head Teachers within Primary Schools

    ERIC Educational Resources Information Center

    Rainer, Paul; Cropley, Brendan; Jarvis, Stuart; Griffiths, Rob

    2012-01-01

    Background: Despite considerable investment in UK government initiatives (e.g., the Physical Education School Sport [PESS] plan) aimed at improving the delivery and quality of physical education (PE) in primary schools, many remaining problems have been highlighted (e.g., facilities; staff training). It is suggested that the head teacher (school…

  16. Fishes in a changing world: learning from the past to promote sustainability of fish populations.

    PubMed

    Gordon, T A C; Harding, H R; Clever, F K; Davidson, I K; Davison, W; Montgomery, D W; Weatherhead, R C; Windsor, F M; Armstrong, J D; Bardonnet, A; Bergman, E; Britton, J R; Côté, I M; D'agostino, D; Greenberg, L A; Harborne, A R; Kahilainen, K K; Metcalfe, N B; Mills, S C; Milner, N J; Mittermayer, F H; Montorio, L; Nedelec, S L; Prokkola, J M; Rutterford, L A; Salvanes, A G V; Simpson, S D; Vainikka, A; Pinnegar, J K; Santos, E M

    2018-03-01

    Populations of fishes provide valuable services for billions of people, but face diverse and interacting threats that jeopardize their sustainability. Human population growth and intensifying resource use for food, water, energy and goods are compromising fish populations through a variety of mechanisms, including overfishing, habitat degradation and declines in water quality. The important challenges raised by these issues have been recognized and have led to considerable advances over past decades in managing and mitigating threats to fishes worldwide. In this review, we identify the major threats faced by fish populations alongside recent advances that are helping to address these issues. There are very significant efforts worldwide directed towards ensuring a sustainable future for the world's fishes and fisheries and those who rely on them. Although considerable challenges remain, by drawing attention to successful mitigation of threats to fish and fisheries we hope to provide the encouragement and direction that will allow these challenges to be overcome in the future. © 2018 The Authors. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of The Fisheries Society of the British Isles.

  17. Safeguards Considerations for Thorium Fuel Cycles

    DOE PAGES

    Worrall, Louise G.; Worrall, Andrew; Flanagan, George F.; ...

    2016-04-21

    We report that by around 2025, thorium-based fuel cycles are likely to be deployed internationally. States such as China and India are pursuing research, development, and deployment pathways toward a number of commercial-scale thorium fuel cycles, and they are already building test reactors and the associated fuel cycle infrastructure. In the future, the potential exists for these emerging programs to sell, export, and deploy thorium fuel cycle technology in other states. Without technically adequate international safeguards protocols and measures in place, any future potential clandestine misuse of these fuel cycles could go undetected, compromising the deterrent value of these protocolsmore » and measures. The development of safeguards approaches for thorium-based fuel cycles is therefore a matter of some urgency. Yet, the focus of the international safeguards community remains mainly on safeguarding conventional 235U- and 239Pu-based fuel cycles while the safeguards challenges of thorium-uranium fuel cycles remain largely uninvestigated. This raises the following question: Is the International Atomic Energy Agency and international safeguards system ready for thorium fuel cycles? Furthermore, is the safeguards technology of today sufficiently mature to meet the verification challenges posed by thorium-based fuel cycles? In defining these and other related research questions, the objectives of this paper are to identify key safeguards considerations for thorium-based fuel cycles and to call for an early dialogue between the international safeguards and the nuclear fuel cycle communities to prepare for the potential safeguards challenges associated with these fuel cycles. In this paper, it is concluded that directed research and development programs are required to meet the identified safeguards challenges and to take timely action in preparation for the international deployment of thorium fuel cycles.« less

  18. The history of head transplantation: a review.

    PubMed

    Lamba, Nayan; Holsgrove, Daniel; Broekman, Marike L

    2016-12-01

    Since the turn of the last century, the prospect of head transplantation has captured the imagination of scientists and the general public. Recently, head transplant has regained attention in popular media, as neurosurgeons have proposed performing this procedure in 2017. Given the potential impact of such a procedure, we were interested in learning the history of the technical hurdles that need to be overcome, and determine if it is even technically possible to perform such a procedure on humans today. We conducted a historical review of available literature on the technical challenges and developments of head transplantation. The many social, psychological, ethical, religious, cultural, and legal questions of head transplantation were beyond the scope of this review. Our historical review identified the following important technical considerations related to performing a head transplant: maintenance of blood flow to an isolated brain via vessel anastomosis; availability of immunosuppressive agents; spinal anastomosis and fusion following cord transfection; pain control in the recipient. Several animal studies have demonstrated success in maintaining recipient cerebral perfusion and achieving immunosuppression. However, there is currently sparse evidence in favor of successful spinal anastomosis and fusion after transection. While recent publications by an Italian group offer novel approaches to this challenge, research on this topic has been sparse and hinges on procedures performed in animal models in the 1970s. How transferrable these older methods are to the human nervous system is unclear and warrants further exploration. Our review identified several important considerations related to performing a viable head transplantation. Besides the technical challenges that remain, there are important ethical issues to consider, such as exploitation of vulnerable patients and informed consent. Thus, besides the remaining technical challenges, these ethical issues will also need to be addressed before moving these studies to the clinic.

  19. Post-traumatic stress disorder diagnosis in children: challenges and promises

    PubMed Central

    Cohen, Judith A.; Scheeringa, Michael S.

    2009-01-01

    Children and adolescents experience high rates of potentially traumatic experiences. Many children subsequently develop mental health problems, including post-traumatic stress disorder (PTSD) symptoms. Accurately diagnosing PTSD in children is challenging. This paper reviews the following important issues: (i) the specificity of the PTSD diagnosis; (ii) children who are symptomatic and impaired but do not have enough symptoms for the diagnosis of PTSD; (iii) developmental considerations for preschool and schooi-age children; and (iv) a variety of assessment challenges that reflect the difficulty and complexity of interviewing children and caregivers about these symptoms. Despite these challenges, PTSD remains the best construct for clinical and research work with trauma survivors. Pediatric PTSD criteria are valuable for identifying children at risk and in need of treatment and can be even more helpful when developmentally modified in ways that are discussed. PMID:19432391

  20. 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.

  1. Progress and challenges of disaster health management in China: a scoping review

    PubMed Central

    Zhong, Shuang; Clark, Michele; Hou, Xiang-Yu; Zang, Yuli; FitzGerald, Gerard

    2014-01-01

    Background Despite the importance of an effective health system response to various disasters, relevant research is still in its infancy, especially in middle- and low-income countries. Objective This paper provides an overview of the status of disaster health management in China, with its aim to promote the effectiveness of the health response for reducing disaster-related mortality and morbidity. Design A scoping review method was used to address the recent progress of and challenges to disaster health management in China. Major health electronic databases were searched to identify English and Chinese literature that were relevant to the research aims. Results The review found that since 2003 considerable progress has been achieved in the health disaster response system in China. However, there remain challenges that hinder effective health disaster responses, including low standards of disaster-resistant infrastructure safety, the lack of specific disaster plans, poor emergency coordination between hospitals, lack of portable diagnostic equipment and underdeveloped triage skills, surge capacity, and psychological interventions. Additional challenges include the fragmentation of the emergency health service system, a lack of specific legislation for emergencies, disparities in the distribution of funding, and inadequate cost-effective considerations for disaster rescue. Conclusions One solution identified to address these challenges appears to be through corresponding policy strategies at multiple levels (e.g. community, hospital, and healthcare system level). PMID:25215910

  2. Telecommuting: Occupational health considerations for employee health and safety.

    PubMed

    Healy, M L

    2000-06-01

    1. Information technology has moved "work" out of a centralized location. Employees who telecommute pose significant challenges and considerations for the practice of occupational health nursing. 2. Employer and employee benefits associated with telecommuting are reportedly associated with high levels of job satisfaction. However, the occupational health and safety risks of this new work environment need to be fully assessed and understood. 3. The ergonomic controls to minimize the risk of repetitive motion injuries are the same for both office and home locations. Additional attention need to be paid to implementing risk controls for other physical hazards and psychosocial considerations, as well as personal safety and security issues. 4. The scope of occupational health nursing practice needs to remain dynamic, recognizing the impact new technologies have on the workplace, to continue to meet the needs of the changing workplace.

  3. Everywhere You Go, Everyone Is Saying Condom, Condom. but Are They Being Used Consistently? Reflections of South African Male Students about Male and Female Condom Use

    ERIC Educational Resources Information Center

    Mantell, Joanne E.; Smit, Jennifer A.; Beksinska, Mags; Scorgie, Fiona; Milford, Cecilia; Balch, Erin; Mabude, Zonke; Smith, Emily; Adams-Skinner, Jessica; Exner, Theresa M.; Hoffman, Susie; Stein, Zena A.

    2011-01-01

    Young men in South Africa can play a critical role in preventing new human immunodeficiency virus (HIV) infections, yet are seldom targeted for HIV prevention. While reported condom use at last sex has increased considerably among young people, consistent condom use remains a challenge. In this study, 74 male higher education students gave their…

  4. Rethinking health research capacity strengthening

    PubMed Central

    Vasquez, Emily; Hirsch, Jennifer S.; Giang, Le Minh; Parker, Richard G.

    2013-01-01

    Health research capacity strengthening (HRCS) is a strategy implemented worldwide to improve the ability of developing countries to tackle the persistent and disproportionate burdens of disease they face. Drawing on a review of existing HRCS literature and our experiences over the course of an NIH-funded HRCS project in Vietnam, we summarise major challenges to the HRCS enterprise at the interpersonal, institutional and macro levels. While over the course of several decades of HRCS initiatives many of these challenges have been well documented, we highlight several considerations that remain under-articulated. We advance critical considerations of the HRCS enterprise by discussing 1) how the organisation of US public health funding shapes the ecology of knowledge production in low- and middle-income country contexts, 2) the barriers US researchers face to effectively collaborating in capacity strengthening for research-to-policy translation, and 3) the potential for unintentional negative consequences if HRCS efforts are not sufficiently reflexive about the limitations of dominant paradigms in public health research and intervention. PMID:23651463

  5. Update on Islet Transplantation

    PubMed Central

    McCall, Michael; James Shapiro, A.M.

    2012-01-01

    Clinical islet transplantation has progressed considerably over the past 12 years, and >750 patients with type 1 diabetes have received islet transplants internationally over this time. Many countries are beginning to accept the transition from research to accepted and funded clinical care, especially for patients with brittle control that cannot be stabilized by more conventional means. Major challenges remain, including the need for more than one donor, and the requirement for potent, chronic immunosuppression. Combining immunological tolerance both to allo- and autoantigens, and a limitless expandable source of stem cell- or xenograft-derived insulin-secreting cells represent remaining hurdles in moving this effective treatment to a potential cure for all those with type 1 or 2 diabetes. PMID:22762022

  6. Gender identity disorder and its medico-legal considerations.

    PubMed

    Sharma, B R

    2007-01-01

    The general belief among behavioural scientists and physicians is that gender identity disorder or transsexualism is an identifiable and incapacitating disease which can be diagnosed and successfully treated by reassignment surgery in carefully selected patients. Although many advances have been made in the reassignment surgery techniques, phalloplasty still remains a major challenge; to date, no ideal technique has been developed. The new gender created by the reassignment surgery has, in turn, led to many legal complications for post-operative transsexuals because, in many developed and the developing countries, transsexuals are not given a legal identity, thereby adding to their agonies and miseries. This article examines the historical perspective, genesis and management of gender identity disorder, or transsexualism, and draws attention to the medico-legal considerations.

  7. Advancements in Nanomedicine for Multiple Myeloma.

    PubMed

    Detappe, Alexandre; Bustoros, Mark; Mouhieddine, Tarek H; Ghoroghchian, P Peter

    2018-06-01

    In the past decades, considerable progress has been made in our understanding and treatment of multiple myeloma. Several challenges remain including our abilities to longitudinally image tumor responses to treatment, to combine various therapeutic agents with different mechanisms of action but with overlapping toxicities, and to efficiently harness the power of the immune system to augment remission and/or to induce permanent cures. Nanomedicine may help to address many of these outstanding issues, affording novel diagnostic capabilities and offering disruptive technologies that promise to revolutionize treatment. Here, we review recent developments and the future of nanomedicine for multiple myeloma, highlighting new considerations in nanoparticle designs that may help to augment active targeting, to facilitate longitudinal imaging, and to improve drug delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Laparoscopic partial nephrectomy: Technical considerations and an update

    PubMed Central

    Dominguez-Escrig, Jose L; Vasdev, Nikhil; O’Riordon, Anna; Soomro, Naeem

    2011-01-01

    The widespread use of radiological imaging (ultrasound, computed tomography and magnetic resonance imaging) has resulted in a steady increase in the incidental diagnosis of small renal masses. While open partial nephrectomy (OPN) remains the reference standard for the management of small renal masses, laparoscopic partial nephrectomy (LPN) continues to evolve. LPN is currently advocated to be at par with OPN oncologically. The steep learning curve and technical demand of LPN make it challenging to establish this as a new procedure. We present a detailed up-to-date review on the previous, current and planned technical considerations for the use of LPN, highlighting important surgical techniques, including single-port and robotic surgery, techniques on improving intra-operative haemostasis and the management of complications specific to LPN. PMID:22022109

  9. The Challenge of Understanding Cerebral White Matter Injury in the Premature Infant

    PubMed Central

    Elitt, Christopher M.; Rosenberg, Paul A.

    2014-01-01

    White matter injury in the premature infant leads to motor and more commonly behavioral and cognitive problems that are a tremendous burden to society. While there has been much progress in understanding unique vulnerabilities of developing oligodendrocytes over the past 30 years, there remain no proven therapies for the premature infant beyond supportive care. The lack of translational progress may be partially explained by the challenge of developing relevant animal models when the etiology remains unclear, as is the case in this disorder. There has been an emphasis on hypoxia-ischemia and infection/inflammation as upstream etiologies, but less consideration of other contributory factors. This review highlights the evolution of white matter pathology in the premature infant, discusses the prevailing proposed etiologies, critically analyzes a sampling of common animal models and provides detailed support for our hypothesis that nutritional and hormonal deprivation may be additional factors playing critical and overlooked roles in white matter pathology in the premature infant. PMID:24838063

  10. Yielding to desire: the durability of affective preferences.

    PubMed

    Rapp, David N; Jacovina, Matthew E; Slaten, Daniel G; Krause, Elise

    2014-09-01

    People's expectations about the future are guided not just by the contingencies of situations but also by what they hope or wish will happen next. These preferences can inform predictions that run counter to what should or must occur based on the logic of unfolding events. Effects of this type have been regularly identified in studies of judgment and decision making, with individuals' choices often reflecting emotional rather than rational influences. Encouraging individuals to rely less on their emotional considerations has proven a challenge as affective responses are generated quickly and are seemingly informative for decisions. In 6 experiments we examined whether individuals could be encouraged to rely less on their affective preferences when making judgments about future events. Participants read stories in which contexts informed the likelihood of events in ways that might run counter to their preferential investments in particular outcomes. While being less than relevant given the logic of events, participants' affective considerations remained influential despite time allotted for predictive reflection. In contrast, instructional warnings helped attenuate the influence of affective considerations, even under conditions previously shown to encourage preferential biases. The findings are discussed with respect to factors that mediate preference effects, and highlight challenges for overcoming people's reliance on affective contributors to everyday judgments and comprehension.

  11. Mandible Fractures

    PubMed Central

    Pickrell, Brent B.; Serebrakian, Arman T.; Maricevich, Renata S.

    2017-01-01

    Mandible fractures account for a significant portion of maxillofacial injuries and the evaluation, diagnosis, and management of these fractures remain challenging despite improved imaging technology and fixation techniques. Understanding appropriate surgical management can prevent complications such as malocclusion, pain, and revision procedures. Depending on the type and location of the fractures, various open and closed surgical reduction techniques can be utilized. In this article, the authors review the diagnostic evaluation, treatment options, and common complications of mandible fractures. Special considerations are described for pediatric and atrophic mandibles. PMID:28496390

  12. Mandible Fractures.

    PubMed

    Pickrell, Brent B; Serebrakian, Arman T; Maricevich, Renata S

    2017-05-01

    Mandible fractures account for a significant portion of maxillofacial injuries and the evaluation, diagnosis, and management of these fractures remain challenging despite improved imaging technology and fixation techniques. Understanding appropriate surgical management can prevent complications such as malocclusion, pain, and revision procedures. Depending on the type and location of the fractures, various open and closed surgical reduction techniques can be utilized. In this article, the authors review the diagnostic evaluation, treatment options, and common complications of mandible fractures. Special considerations are described for pediatric and atrophic mandibles.

  13. Surgical Management of Chyloptysis.

    PubMed

    Gillaspie, Erin A; Lim, Kaiser; Nichols, Francis C

    2018-02-01

    Chyloptysis is a rare clinical presentation. Diagnosis is challenging and requires recognition of milky-sputum or bronchial casts. We describe a case of chyloptysis secondary to thoracic lymphangiectasia that necessitated surgical ligation of the main thoracic duct and accessory branches. The patient had no postoperative complications, and at 6-month follow-up remained symptom-free. A paucity of literature describes the management of chyloptysis. We review diagnosis, treatment considerations and operative principles. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  14. On axionic field ranges, loopholes and the weak gravity conjecture

    DOE PAGES

    Brown, Jon; Cottrell, William; Shiu, Gary; ...

    2016-04-05

    Here, we clarify some aspects of the impact that the Weak Gravity Conjecture has on models of (generalized) natural inflation. In particular we address certain technical and conceptual concerns recently raised regarding the stringent constraints and conclusions found in our previous work. We also point out the difficulties faced by attempts to evade these constraints. Furthermore, these new considerations improve the understanding of the quantum gravity constraints we found and further support the conclusion that it remains challenging for axions to drive natural inflation.

  15. Considerations, challenges and future of anti-TNF therapy in treating inflammatory bowel disease.

    PubMed

    Pouillon, Lieven; Bossuyt, Peter; Peyrin-Biroulet, Laurent

    2016-10-01

    Crohn's disease (CD) and ulcerative colitis (UC) are chronic disabling conditions. Monoclonal antibody therapy directed against tumor necrosis factor-alpha (anti-TNF) has revolutionized the care of patients with inflammatory bowel disease (IBD). Considerations before starting anti-TNF therapy are highlighted: the best time to start with anti-TNF therapy, either alone or in combination with an immunomodulator, the choice of an anti-TNF agent and the contra-indications to anti-TNF therapy. Primary nonresponse and secondary loss of response are discussed. De-escalating therapy, the role of therapeutic drug monitoring and the use of biosimilars, are handled. Finally, the future directions of anti-TNF therapy are emphasized. Anti-TNF therapy remains the cornerstone in the treatment of IBD. When initiating long-term therapy, safety and cost issues are of great importance. The therapeutic armamentarium in the treatment of IBD is rapidly growing. Therefore, the challenge is to optimize the use and refine the exact position of anti-TNF therapy in the near future, with personalized medicine as the ultimate goal.

  16. Human centromere genomics: now it's personal.

    PubMed

    Hayden, Karen E

    2012-07-01

    Advances in human genomics have accelerated studies in evolution, disease, and cellular regulation. However, centromere sequences, defining the chromosomal interface with spindle microtubules, remain largely absent from ongoing genomic studies and disconnected from functional, genome-wide analyses. This disparity results from the challenge of predicting the linear order of multi-megabase-sized regions that are composed almost entirely of near-identical satellite DNA. Acknowledging these challenges, the field of human centromere genomics possesses the potential to rapidly advance given the availability of individual, or personalized, genome projects matched with the promise of long-read sequencing technologies. Here I review the current genomic model of human centromeres in consideration of those studies involving functional datasets that examine the role of sequence in centromere identity.

  17. Data science, learning, and applications to biomedical and health sciences.

    PubMed

    Adam, Nabil R; Wieder, Robert; Ghosh, Debopriya

    2017-01-01

    The last decade has seen an unprecedented increase in the volume and variety of electronic data related to research and development, health records, and patient self-tracking, collectively referred to as Big Data. Properly harnessed, Big Data can provide insights and drive discovery that will accelerate biomedical advances, improve patient outcomes, and reduce costs. However, the considerable potential of Big Data remains unrealized owing to obstacles including a limited ability to standardize and consolidate data and challenges in sharing data, among a variety of sources, providers, and facilities. Here, we discuss some of these challenges and potential solutions, as well as initiatives that are already underway to take advantage of Big Data. © 2017 New York Academy of Sciences.

  18. Constraint-based stoichiometric modelling from single organisms to microbial communities

    PubMed Central

    Olivier, Brett G.; Bruggeman, Frank J.; Teusink, Bas

    2016-01-01

    Microbial communities are ubiquitously found in Nature and have direct implications for the environment, human health and biotechnology. The species composition and overall function of microbial communities are largely shaped by metabolic interactions such as competition for resources and cross-feeding. Although considerable scientific progress has been made towards mapping and modelling species-level metabolism, elucidating the metabolic exchanges between microorganisms and steering the community dynamics remain an enormous scientific challenge. In view of the complexity, computational models of microbial communities are essential to obtain systems-level understanding of ecosystem functioning. This review discusses the applications and limitations of constraint-based stoichiometric modelling tools, and in particular flux balance analysis (FBA). We explain this approach from first principles and identify the challenges one faces when extending it to communities, and discuss the approaches used in the field in view of these challenges. We distinguish between steady-state and dynamic FBA approaches extended to communities. We conclude that much progress has been made, but many of the challenges are still open. PMID:28334697

  19. Radiation Hardness Assurance (RHA): Challenges and New Considerations

    NASA Technical Reports Server (NTRS)

    Campola, Michael J.

    2017-01-01

    Use of commercial-off-the-shelf (COTS) components and emerging technologies often require space flight missions to accept elevated risk. The Radiation Hardness Assurance (RHA) flow includes environment definition, hazard evaluation, requirements definition, evaluation of design, and design trades to accommodate and mitigate the risk a project or program takes. Depending on the mission profile and environment, different missions may not necessarily benefit from the same risk reduction efforts or cost reduction attempts. While this poses challenges for the radiation engineer, it also presents opportunities to tailor the RHA flow to minimize risk based on the environment or design criticality while remaining within budget. This presentation will focus on an approach to RHA amidst the present challenges, using the same RHA flow as in the past, with examples from recent radiation test results. The current challenges and the types of risk will be identified. How these risks drive requirements development and realization will be explained with examples of device results and data for single event effects (SEE) and in one case total ionizing dose (TID).

  20. Adaptive Management: From More Talk to Real Action

    NASA Astrophysics Data System (ADS)

    Williams, Byron K.; Brown, Eleanor D.

    2014-02-01

    The challenges currently facing resource managers are large-scale and complex, and demand new approaches to balance development and conservation goals. One approach that shows considerable promise for addressing these challenges is adaptive management, which by now is broadly seen as a natural, intuitive, and potentially effective way to address decision-making in the face of uncertainties. Yet the concept of adaptive management continues to evolve, and its record of success remains limited. In this article, we present an operational framework for adaptive decision-making, and describe the challenges and opportunities in applying it to real-world problems. We discuss the key elements required for adaptive decision-making, and their integration into an iterative process that highlights and distinguishes technical and social learning. We illustrate the elements and processes of the framework with some successful on-the-ground examples of natural resource management. Finally, we address some of the difficulties in applying learning-based management, and finish with a discussion of future directions and strategic challenges.

  1. I Got 99 Problems, and eHealth Is One.

    PubMed

    Wass, Sofie; Vimarlund, Vivian

    2017-01-01

    Many eHealth initiatives are never implemented or merely end as pilot projects. Previous studies report that organisational, technical and human issues need to be properly taken into consideration if such initiatives are to be successful. The aim of this paper is to explore whether previously identified challenges within the area have remained in the Swedish eHealth setting or whether they have changed. After interviewing experts in eHealth, we present a classification of areas of concern. Recurrence of previously identified challenges was found, but also new issues were identified. The results of the study indicate that there is a need to consider organisational and semantic issues on both national and international levels. Legal and technical challenges still exist but it seems even more important to support eHealth initiatives financially, increase practitioners' knowledge in health informatics and manage new expectations from patients.

  2. Advances in Candida detection platforms for clinical and point-of-care applications

    PubMed Central

    Safavieh, Mohammadali; Coarsey, Chad; Esiobu, Nwadiuto; Memic, Adnan; Vyas, Jatin Mahesh; Shafiee, Hadi; Asghar, Waseem

    2016-01-01

    Invasive candidiasis remains one of the most serious community and healthcare-acquired infections worldwide. Conventional Candida detection methods based on blood and plate culture are time-consuming and require at least 2–4 days to identify various Candida species. Despite considerable advances for candidiasis detection, the development of simple, compact and portable point-of-care diagnostics for rapid and precise testing that automatically performs cell lysis, nucleic acid extraction, purification and detection still remains a challenge. Here, we systematically review most prominent conventional and nonconventional techniques for the detection of various Candida species, including Candida staining, blood culture, serological testing and nucleic acid-based analysis. We also discuss the most advanced lab on a chip devices for candida detection. PMID:27093473

  3. Community-level climate change vulnerability research: trends, progress, and future directions

    NASA Astrophysics Data System (ADS)

    McDowell, Graham; Ford, James; Jones, Julie

    2016-03-01

    This study systematically identifies, characterizes, and critically evaluates community-level climate change vulnerability assessments published over the last 25 years (n = 274). We find that while the field has advanced considerably in terms of conceptual framing and methodological approaches, key shortcomings remain in how vulnerability is being studied at the community-level. We argue that vulnerability research needs to more critically engage with the following: methods for evaluating future vulnerability, the relevance of vulnerability research for decision-making, interdependencies between social and ecological systems, attention to researcher / subject power dynamics, critical interpretation of key terms, and consideration of the potentially positive opportunities presented by a changing climate. Addressing these research needs is necessary for generating knowledge that supports climate-affected communities in navigating the challenges and opportunities ahead.

  4. Health economics and European Renal Best Practice--is it time to bring health economics into evidence-based guideline production in Europe?

    PubMed

    Haller, Maria C; Vanholder, Raymond; Oberbauer, Rainer; Zoccali, Carmine; Van Biesen, Wim

    2014-11-01

    Medical management of patients with kidney disease is complex and resource intensive. In times of limited health care budgets, economic evaluations have become more important over the past few years in identifying interventions with a beneficial cost-effectiveness to maximize the benefits served from the available resources. However, integrating evidence from health-economic evaluations into clinical practice guidelines remains a challenge. European Renal Best Practice (ERBP), the official guideline body of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) herewith presents some lines of thought that need consideration in the discussion on incorporating health-economic considerations into clinical guideline development. © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  5. Retirement-from-sport considerations following pediatric sports-related concussion: case illustrations and institutional approach.

    PubMed

    Ellis, Michael J; McDonald, Patrick J; Cordingley, Dean; Mansouri, Behzad; Essig, Marco; Ritchie, Lesley

    2016-04-01

    The decision to advise an athlete to retire from sports following sports-related concussion (SRC) remains a persistent challenge for physicians. In the absence of strong empirical evidence to support recommendations, clinical decision making must be individualized and should involve a multidisciplinary team of experts in concussion and traumatic brain injury. Although previous authors have advocated for a more conservative approach to these issues in child and adolescent athletes, there are few reports outlining considerations for this process among this unique population. Here, the authors use multiple case illustrations to discuss 3 subgroups of clinical considerations for sports retirement among pediatric SRC patients including the following: those with structural brain abnormalities identified on neuroimaging, those presenting with focal neurological deficits and abnormalities on physical examination, and those in whom the cumulative or prolonged effects of concussion are suspected or demonstrated. The authors' evolving multidisciplinary institutional approach to return-to-play and retirement decision making in pediatric SRC is also presented.

  6. Chronic hypersensitivity pneumonitis: important considerations in the work-up of this fibrotic lung disease.

    PubMed

    Glazer, Craig S

    2015-03-01

    Chronic hypersensitivity pneumonitis is increasingly recognized as an important mimic of other fibrotic lung diseases. This review will summarize recent data regarding the importance and difficulty of determining causative exposures both for accurate diagnosis and prognosis, and describe the expanded pathologic spectrum of the disease, the effects of fibrosis on prognosis and challenges in the diagnostic evaluation. Several recent publications show the potential pathologic patterns induced by chronic hypersensitivity pneumonitis are broader than the classic triad of bronchiolitis, interstitial infiltrates and granulomas. Other pathologic patterns include nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, bronchiolitis and airway centric fibrosis. Detecting a causative antigen in fibrotic hypersensitivity pneumonitis is challenging but critically important both for accurate diagnosis and improved prognosis. The prognosis in hypersensitivity pneumonitis worsens in the presence of fibrosis, but it remains significantly better than idiopathic pulmonary fibrosis. Hypersensitivity pneumonitis is increasingly recognized as an important cause of fibrotic interstitial lung disease. Hypersensitivity pneumonitis demonstrates a remarkable tendency to mimic other idiopathic interstitial pneumonias. A detailed exposure history remains a cornerstone of diagnosis and management.

  7. Dengue vaccines: recent developments, ongoing challenges and current candidates

    PubMed Central

    McArthur, Monica A.; Sztein, Marcelo B.; Edelman, Robert

    2013-01-01

    Summary Dengue is among the most prevalent and important arbovirus diseases of humans. In order to effectively control this rapidly spreading disease, control of the vector mosquito and a safe and efficacious vaccine are critical. Despite considerable efforts, the development of a successful vaccine has remained elusive. Multiple factors have complicated the creation of a successful vaccine, not the least of which are the complex, immune-mediated responses against four antigenically distinct serotypes necessitating a tetravalent vaccine providing long lasting protective immunity. Despite the multiple impediments, there are currently many promising vaccine candidates in pre-clinical and clinical development. Here we review the recent advances in dengue virus vaccine development and briefly discuss the challenges associated with the use of these vaccines as a public health tool. PMID:23984962

  8. The economic evaluation of personalised oncology medicines: ethical challenges.

    PubMed

    Lewis, Jan R R; Lipworth, Wendy L; Kerridge, Ian H; Day, Richard O

    2013-10-07

    Insights into the molecular drivers of cancer are providing opportunities for the development of new targeted treatments and more personalised approaches to cancer management. Drugs targeting mutant epidermal growth factor receptors, such as erlotinib and gefitinib, may provide more effective, safer and better tolerated treatment options compared with chemotherapy among appropriately selected patients with advanced non-small cell lung cancer (NSCLC). First-line access to these newer treatments remains unfunded after several considerations by the Pharmaceutical Benefits Advisory Committee and their assessment that these are not cost-effective treatments. We suggest that there may be evidentiary and ethical challenges associated with the assessment of the cost-effectiveness of personalised oncology medicines in Australia, and that a new approach is needed to determine the value and cost-effectiveness of personalised medicine.

  9. Spatially explicit data: stewardship and ethical challenges in science.

    PubMed

    Hartter, Joel; Ryan, Sadie J; Mackenzie, Catrina A; Parker, John N; Strasser, Carly A

    2013-09-01

    Scholarly communication is at an unprecedented turning point created in part by the increasing saliency of data stewardship and data sharing. Formal data management plans represent a new emphasis in research, enabling access to data at higher volumes and more quickly, and the potential for replication and augmentation of existing research. Data sharing has recently transformed the practice, scope, content, and applicability of research in several disciplines, in particular in relation to spatially specific data. This lends exciting potentiality, but the most effective ways in which to implement such changes, particularly for disciplines involving human subjects and other sensitive information, demand consideration. Data management plans, stewardship, and sharing, impart distinctive technical, sociological, and ethical challenges that remain to be adequately identified and remedied. Here, we consider these and propose potential solutions for their amelioration.

  10. Modeling nanomaterial environmental fate in aquatic systems.

    PubMed

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

    2015-03-03

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

  11. Applying evolutionary concepts to wildlife disease ecology and management

    PubMed Central

    Vander Wal, Eric; Garant, Dany; Calmé, Sophie; Chapman, Colin A; Festa-Bianchet, Marco; Millien, Virginie; Rioux-Paquette, Sébastien; Pelletier, Fanie

    2014-01-01

    Existing and emerging infectious diseases are among the most pressing global threats to biodiversity, food safety and human health. The complex interplay between host, pathogen and environment creates a challenge for conserving species, communities and ecosystem functions, while mediating the many known ecological and socio-economic negative effects of disease. Despite the clear ecological and evolutionary contexts of host–pathogen dynamics, approaches to managing wildlife disease remain predominantly reactionary, focusing on surveillance and some attempts at eradication. A few exceptional studies have heeded recent calls for better integration of ecological concepts in the study and management of wildlife disease; however, evolutionary concepts remain underused. Applied evolution consists of four principles: evolutionary history, genetic and phenotypic variation, selection and eco-evolutionary dynamics. In this article, we first update a classical framework for understanding wildlife disease to integrate better these principles. Within this framework, we explore the evolutionary implications of environment–disease interactions. Subsequently, we synthesize areas where applied evolution can be employed in wildlife disease management. Finally, we discuss some future directions and challenges. Here, we underscore that despite some evolutionary principles currently playing an important role in our understanding of disease in wild animals, considerable opportunities remain for fostering the practice of evolutionarily enlightened wildlife disease management. PMID:25469163

  12. Applying evolutionary concepts to wildlife disease ecology and management.

    PubMed

    Vander Wal, Eric; Garant, Dany; Calmé, Sophie; Chapman, Colin A; Festa-Bianchet, Marco; Millien, Virginie; Rioux-Paquette, Sébastien; Pelletier, Fanie

    2014-08-01

    Existing and emerging infectious diseases are among the most pressing global threats to biodiversity, food safety and human health. The complex interplay between host, pathogen and environment creates a challenge for conserving species, communities and ecosystem functions, while mediating the many known ecological and socio-economic negative effects of disease. Despite the clear ecological and evolutionary contexts of host-pathogen dynamics, approaches to managing wildlife disease remain predominantly reactionary, focusing on surveillance and some attempts at eradication. A few exceptional studies have heeded recent calls for better integration of ecological concepts in the study and management of wildlife disease; however, evolutionary concepts remain underused. Applied evolution consists of four principles: evolutionary history, genetic and phenotypic variation, selection and eco-evolutionary dynamics. In this article, we first update a classical framework for understanding wildlife disease to integrate better these principles. Within this framework, we explore the evolutionary implications of environment-disease interactions. Subsequently, we synthesize areas where applied evolution can be employed in wildlife disease management. Finally, we discuss some future directions and challenges. Here, we underscore that despite some evolutionary principles currently playing an important role in our understanding of disease in wild animals, considerable opportunities remain for fostering the practice of evolutionarily enlightened wildlife disease management.

  13. On the role of plant mitochondrial metabolism and its impact on photosynthesis in both optimal and sub-optimal growth conditions.

    PubMed

    Araújo, Wagner L; Nunes-Nesi, Adriano; Fernie, Alisdair R

    2014-02-01

    Given that the pathways of photosynthesis and respiration catalyze partially opposing processes, it follows that their relative activities must be carefully regulated within plant cells. Recent evidence has shown that the components of the mitochondrial electron transport chain are essential for the proper maintenance of intracellular redox gradients, to allow considerable rates of photorespiration and in turn efficient photosynthesis. Thus considerable advances have been made in understanding the interaction between respiration and photosynthesis during the last decades and the potential mechanisms linking mitochondrial function and photosynthetic efficiency will be reviewed. Despite the fact that manipulation of various steps of mitochondrial metabolism has been demonstrated to alter photosynthesis under optimal growth conditions, it is likely that these changes will, by and large, not be maintained under sub-optimal situations. Therefore producing plants to meet this aim remains a critical challenge. It is clear, however, that although there have been a range of studies analysing changes in respiratory and photosynthetic rates in response to light, temperature and CO2, our knowledge of the environmental impact on these processes and its linkage still remains fragmented. We will also discuss the metabolic changes associated to plant respiration and photosynthesis as important components of the survival strategy as they considerably extend the period that a plant can withstand to a stress situation.

  14. Knitting the Threads of Silk through Time: Behçet's Disease—Past, Present, and Future

    PubMed Central

    Stack, Austin G.; Fraser, Alexander D.

    2017-01-01

    Behçet's disease (BD) is a chronic relapsing vasculitis that affects vessels of all types and sizes with a broad spectrum of phenotypic heterogeneity and complex immunopathogenesis. Efforts by the scientific community to resolve the unmet needs of BD and gaps in our knowledge have been hampered by considerable challenges that primarily relate to the rare nature of the disease in many parts of the world and its heterogeneity. Controversies remain in many aspects of the disease including the diagnostic criteria, immunopathogenesis and biomarker discovery, geographical variation, and therapeutic considerations. In this review, we highlight recent advances in our scientific understanding of BD, shed new insights into diagnostic and treatment strategies, and discuss residual gaps in our knowledge that will serve as the basis for current and future research. PMID:29081805

  15. Computational design of water-soluble α-helical barrels.

    PubMed

    Thomson, Andrew R; Wood, Christopher W; Burton, Antony J; Bartlett, Gail J; Sessions, Richard B; Brady, R Leo; Woolfson, Derek N

    2014-10-24

    The design of protein sequences that fold into prescribed de novo structures is challenging. General solutions to this problem require geometric descriptions of protein folds and methods to fit sequences to these. The α-helical coiled coils present a promising class of protein for this and offer considerable scope for exploring hitherto unseen structures. For α-helical barrels, which have more than four helices and accessible central channels, many of the possible structures remain unobserved. Here, we combine geometrical considerations, knowledge-based scoring, and atomistic modeling to facilitate the design of new channel-containing α-helical barrels. X-ray crystal structures of the resulting designs match predicted in silico models. Furthermore, the observed channels are chemically defined and have diameters related to oligomer state, which present routes to design protein function. Copyright © 2014, American Association for the Advancement of Science.

  16. The Computational Fluid Dynamics Rupture Challenge 2013—Phase I: prediction of rupture status in intracranial aneurysms.

    PubMed

    Janiga, G; Berg, P; Sugiyama, S; Kono, K; Steinman, D A

    2015-03-01

    Rupture risk assessment for intracranial aneurysms remains challenging, and risk factors, including wall shear stress, are discussed controversially. The primary purpose of the presented challenge was to determine how consistently aneurysm rupture status and rupture site could be identified on the basis of computational fluid dynamics. Two geometrically similar MCA aneurysms were selected, 1 ruptured, 1 unruptured. Participating computational fluid dynamics groups were blinded as to which case was ruptured. Participants were provided with digitally segmented lumen geometries and, for this phase of the challenge, were free to choose their own flow rates, blood rheologies, and so forth. Participants were asked to report which case had ruptured and the likely site of rupture. In parallel, lumen geometries were provided to a group of neurosurgeons for their predictions of rupture status and site. Of 26 participating computational fluid dynamics groups, 21 (81%) correctly identified the ruptured case. Although the known rupture site was associated with low and oscillatory wall shear stress, most groups identified other sites, some of which also experienced low and oscillatory shear. Of the 43 participating neurosurgeons, 39 (91%) identified the ruptured case. None correctly identified the rupture site. Geometric or hemodynamic considerations favor identification of rupture status; however, retrospective identification of the rupture site remains a challenge for both engineers and clinicians. A more precise understanding of the hemodynamic factors involved in aneurysm wall pathology is likely required for computational fluid dynamics to add value to current clinical decision-making regarding rupture risk. © 2015 by American Journal of Neuroradiology.

  17. Randomization Does Not Help Much, Comparability Does

    PubMed Central

    Saint-Mont, Uwe

    2015-01-01

    According to R.A. Fisher, randomization “relieves the experimenter from the anxiety of considering innumerable causes by which the data may be disturbed.” Since, in particular, it is said to control for known and unknown nuisance factors that may considerably challenge the validity of a result, it has become very popular. This contribution challenges the received view. First, looking for quantitative support, we study a number of straightforward, mathematically simple models. They all demonstrate that the optimism surrounding randomization is questionable: In small to medium-sized samples, random allocation of units to treatments typically yields a considerable imbalance between the groups, i.e., confounding due to randomization is the rule rather than the exception. In the second part of this contribution, the reasoning is extended to a number of traditional arguments in favour of randomization. This discussion is rather non-technical, and sometimes touches on the rather fundamental Frequentist/Bayesian debate. However, the result of this analysis turns out to be quite similar: While the contribution of randomization remains doubtful, comparability contributes much to a compelling conclusion. Summing up, classical experimentation based on sound background theory and the systematic construction of exchangeable groups seems to be advisable. PMID:26193621

  18. Fetal and maternal outcomes in pregnancies complicated with fetal macrosomia.

    PubMed

    Alsammani, Mohamed Alkahatim; Ahmed, Salah Roshdy

    2012-06-01

    Fetal macrosomia remains a considerable challenge in current obstetrics due to the fetal and maternal complications associated with this condition. This study was designed to determine the prevalence of fetal macrosomia and associated fetal and maternal morbidity and mortality in the Al Qassim Region of Saudi Arabia. This register-based study was conducted from January 1, 2011 through December 30, 2011 at the Maternity and Child Hospital, Qassim, Saudi Arabia. Macrosomia was defined as birth weight of 4 kg or greater. Malformed babies and those born dead were excluded. The total number of babies delivered was 9241; of these, 418 were macrosomic. Thus, the prevalence of fetal macrosomia was 4.5%. The most common maternal complications were postpartum hemorrhage (5 cases, 1.2%), perineal tear (7 cases, 1.7%), cervical lacerations (3 cases, 0.7%), and shoulder dystocia (40 cases, 9.6%) that resulted in 4 cases of Erb's palsy (0.96%), and 6 cases of bone fractures (1.4%). The rate of cesarean section among women delivering macrosomic babies was 47.6% (199), while 52.4% (219) delivered vaginally. Despite extensive efforts to reduce fetal and maternal complications associated with macrosomia, considerable fetal and maternal morbidity remain associated with this condition.

  19. Numerical simulations of merging black holes for gravitational-wave astronomy

    NASA Astrophysics Data System (ADS)

    Lovelace, Geoffrey

    2014-03-01

    Gravitational waves from merging binary black holes (BBHs) are among the most promising sources for current and future gravitational-wave detectors. Accurate models of these waves are necessary to maximize the number of detections and our knowledge of the waves' sources; near the time of merger, the waves can only be computed using numerical-relativity simulations. For optimal application to gravitational-wave astronomy, BBH simulations must achieve sufficient accuracy and length, and all relevant regions of the BBH parameter space must be covered. While great progress toward these goals has been made in the almost nine years since BBH simulations became possible, considerable challenges remain. In this talk, I will discuss current efforts to meet these challenges, and I will present recent BBH simulations produced using the Spectral Einstein Code, including a catalog of publicly available gravitational waveforms [black-holes.org/waveforms]. I will also discuss simulations of merging black holes with high mass ratios and with spins nearly as fast as possible, the most challenging regions of the BBH parameter space.

  20. Operational challenges in delivering CD4 diagnostics in sub-Saharan Africa.

    PubMed

    Thairu, L; Katzenstein, D; Israelski, D

    2011-07-01

    Access to reliable and low cost CD4 T-cell enumeration to stage illness and monitor anti-retroviral therapy remains elusive in resource-limited settings. We report challenges in delivering CD4 testing using the microcapillary Fluorescence-Activated Cell Sorter (FACS) methodology (Guava EasyCD4 instrument Guava Technologies, Hayward) in Burkina Faso and Zimbabwe. Resources, instruments, reagents, and training were provided to local laboratories within the existing infrastructure and data on CD4 were collected from routine laboratory testing. Challenges encountered included frequent instrument breakdown; poor manufacturer maintenance; difficulties in managing reagent stocks; high technician turnover; reliance on antiquated data management systems; redundant service provision; and lack of repeat testing in male HIV+ patients and in patients with higher CD4 counts after initial staging. While adopting newer, less expensive technologies such as fluorescent platforms and point of care tests can facilitate access to lower cost CD4 testing, our experience suggests that supply chain, corporate commitment to implementation, and community factors also require consideration.

  1. Current status and challenges for automotive battery production technologies

    NASA Astrophysics Data System (ADS)

    Kwade, Arno; Haselrieder, Wolfgang; Leithoff, Ruben; Modlinger, Armin; Dietrich, Franz; Droeder, Klaus

    2018-04-01

    Production technology for automotive lithium-ion battery (LIB) cells and packs has improved considerably in the past five years. However, the transfer of developments in materials, cell design and processes from lab scale to production scale remains a challenge due to the large number of consecutive process steps and the significant impact of material properties, electrode compositions and cell designs on processes. This requires an in-depth understanding of the individual production processes and their interactions, and pilot-scale investigations into process parameter selection and prototype cell production. Furthermore, emerging process concepts must be developed at lab and pilot scale that reduce production costs and improve cell performance. Here, we present an introductory summary of the state-of-the-art production technologies for automotive LIBs. We then discuss the key relationships between process, quality and performance, as well as explore the impact of materials and processes on scale and cost. Finally, future developments and innovations that aim to overcome the main challenges are presented.

  2. 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.

  3. Current state and challenges in developing oral vaccines.

    PubMed

    Vela Ramirez, Julia E; Sharpe, Lindsey A; Peppas, Nicholas A

    2017-05-15

    While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection. However, oral delivery is challenging, requiring formulations to overcome the harsh gastrointestinal (GI) environment and avoid tolerance induction to achieve effective protection. Here we address the rationale for oral vaccines, including key biological and physicochemical considerations for next-generation oral vaccine design. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. A Rural Implementation of a 52 Node Mixed Wireless Mesh Network in Macha, Zambia

    NASA Astrophysics Data System (ADS)

    Backens, Jonathan; Mweemba, Gregory; van Stam, Gertjan

    In spite of increasing international and academic attention, there remains many challenges facing real world implementations of developing technologies. There has been considerable hype behind Wireless Mesh Networking as the ubiquitous solution for rural ICT in the developing world. In this paper, we present the real world rural mesh network implementation in the village of Macha, Zambia and draw both performance conclusions as well as overall experiential conclusions. The purpose of this paper is to introduce and analyze our low cost solution and extrapolate future trends for rural ICT implementations in Zambia.

  5. Economic Burden of Clostridium difficile Infection in European Countries.

    PubMed

    Reigadas Ramírez, Elena; Bouza, Emilio Santiago

    2018-01-01

    Clostridium difficile infection (CDI) remains a considerable challenge to health care systems worldwide. Although CDI represents a significant burden on healthcare systems in Europe, few studies have attempted to estimate the consumption of resources associated with CDI in Europe. The reported extra costs attributable to CDI vary widely according to the definitions, design, and methodologies used, making comparisons difficult to perform. In this chapter, the economic burden of healthcare facility-associated CDI in Europe will be assessed, as will other less explored areas such as the economic burden of recurrent CDI, community-acquired CDI, pediatric CDI, and CDI in outbreaks.

  6. Protection of Non-Human Primates against Rabies with an Adenovirus Recombinant Vaccine

    PubMed Central

    Xiang, Z.Q.; Greenberg, L.; Ertl, H. C.; Rupprecht, C.E.

    2014-01-01

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. PMID:24503087

  7. The forest for the trees: tuberculosis control efforts in west Kalimantan.

    PubMed

    Shoeb, Marwa; Lopez de Castilla, Diego; Pottinger, Paul

    2011-01-01

    Alam Sehat Lestari (ASRI), an Indonesian-American, non-profit organization located on the border of Gunung Palung National Park in west Kalimantan on the island of Borneo, is linking the delivery of health care to the conservation of natural resources. The clinic's experience shows that an unconventional 'forests-for-health care' incentive programme can provide a powerful way to break the cycle that links poverty, poor health and environmental destruction around the park. However, the challenges of preventing, diagnosing and treating tuberculosis in this setting remain considerable and success will still depend upon a multilateral collaborative approach.

  8. The role of managed care in improving outcomes in epilepsy.

    PubMed

    Stern, John M

    2011-07-01

    The burden of epilepsy for patients and payers is large and onerous. The heterogeneous nature of the condition and the lack of diagnostic or treatment biomarkers present considerable clinical challenge. Despite expansion of the treatment armamentarium, selection of maximally appropriate therapy for individual patients remains a challenge, especially in those with treatment-refractory epilepsy. While numerous factors play a role in resolving these uncertainties, 3 key factors stand out. An overwhelming quantity of clinical data support the notion that the most effective therapies-measured by the ability to control seizures while minimizing adverse effects-are typically the most cost-effective. A second consideration is maximizing adherence to prescribed therapies, which has been an ongoing dilemma in the treatment of epilepsy because the condition occurs episodically. Poor adherence has a profound effect on treatment and costs, and several strategies for improving adherence have been identified. If properly observed, these can improve outcomes and lower expenditures. The third consideration is the monitoring of therapeutic response. This is essentially through ongoing care by the prescriber with careful assessment of seizures, patient satisfaction with treatment, dose-related adverse effects, and the subjective aspects of idiosyncratic toxicity; however, laboratory testing can also have a role. The resources needed to provide this monitoring vary across treatments. From a systemic point of view, engagement of all stakeholders-patients, payers, and physicians-in overseeing the effective and efficient use of healthcare resources will benefit all parties involved.

  9. Biologic Treatments for Sports Injuries II Think Tank—Current Concepts, Future Research, and Barriers to Advancement, Part 2

    PubMed Central

    Murray, Iain R.; LaPrade, Robert F.; Musahl, Volker; Geeslin, Andrew G.; Zlotnicki, Jason P.; Mann, Barton J.; Petrigliano, Frank A.

    2016-01-01

    Rotator cuff tears are common and result in considerable morbidity. Tears within the tendon substance or at its insertion into the humeral head represent a considerable clinical challenge because of the hostile local environment that precludes healing. Tears often progress without intervention, and current surgical treatments are inadequate. Although surgical implants, instrumentation, and techniques have improved, healing rates have not improved, and a high failure rate remains for large and massive rotator cuff tears. The use of biologic adjuvants that contribute to a regenerative microenvironment have great potential for improving healing rates and function after surgery. This article presents a review of current and emerging biologic approaches to augment rotator cuff tendon and muscle regeneration focusing on the scientific rationale, preclinical, and clinical evidence for efficacy, areas for future research, and current barriers to advancement and implementation. PMID:27099865

  10. The impact of human immunodeficiency virus-related diseases on pigmented skin types.

    PubMed

    Ameen, M

    2013-10-01

    Infection with human immunodeficiency virus (HIV) remains a significant problem globally. Early diagnosis and treatment with antiretroviral drugs has considerably improved health outcomes and decreased disease-related morbidity. HIV infection is associated with a wide range of skin disorders enabling dermatologists to diagnose HIV as well as associated opportunistic infections early in the course of disease. Despite concerted efforts by international health organizations to limit disease incidence, the prevalence of HIV infection remains high and is highest in sub-Saharan Africa. The diagnosis of HIV-related skin diseases is challenging as immunosuppression often results in atypical disease presentation. In addition, the clinical presentation will vary in pigmented skin types. The aim of this article is to describe disease variation in pigmented skin types. © 2013 The Author BJD © 2013 British Association of Dermatologists.

  11. Proinflammatory Stem Cell Signaling in Cardiac Ischemia

    PubMed Central

    Herrmann, Jeremy L.; Markel, Troy A.; Abarbanell, Aaron M.; Weil, Brent R.; Wang, Meijing; Wang, Yue; Tan, Jiangning

    2009-01-01

    Abstract Cardiovascular disease remains a leading cause of mortality in developed nations, despite continued advancement in modern therapy. Progenitor and stem cell–based therapy is a novel treatment for cardiovascular disease, and modest benefits in cardiac recovery have been achieved in small clinical trials. This therapeutic modality remains challenged by limitations of low donor-cell survival rates, transient recovery of cardiac function, and the technical difficulty of applying directed cell therapy. Understanding the signaling mechanisms involved in the stem cell response to ischemia has revealed opportunities to modify directly aspects of these pathways to improve their cardioprotective abilities. This review highlights general considerations of stem cell therapy for cardiac disease, reviews the major proinflammatory signaling pathways of mesenchymal stem cells, and reviews ex vivo modifications of stem cells based on these pathways. Antioxid. Redox Signal. 11, 1883–1896. PMID:19187005

  12. Artificial activation of toxin-antitoxin systems as an antibacterial strategy.

    PubMed

    Williams, Julia J; Hergenrother, Paul J

    2012-06-01

    Toxin-antitoxin (TA) systems are unique modules that effect plasmid stabilization via post-segregational killing of the bacterial host. The genes encoding TA systems also exist on bacterial chromosomes, and it has been speculated that these are involved in a variety of cellular processes. Interest in TA systems has increased dramatically over the past 5 years as the ubiquitous nature of TA genes on bacterial genomes has been revealed. The exploitation of TA systems as an antibacterial strategy via artificial activation of the toxin has been proposed and has considerable potential; however, efforts in this area remain in the early stages and several major questions remain. This review investigates the tractability of targeting TA systems to kill bacteria, including fundamental requirements for success, recent advances, and challenges associated with artificial toxin activation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Challenge Activities for the Physical Education Classroom: Considerations

    ERIC Educational Resources Information Center

    McKenzie, Emily; Tapps, Tyler; Fink, Kevin; Symonds, Matthew L.

    2018-01-01

    The purpose of this article is to provide physical education teachers with the tools to develop and implement challenge course-like activities in their physical education classes. The article also covers environmental considerations for teachers who have the desire to create a challenge-based classroom setting in order to reach a wider and more…

  14. 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.

  15. Assessment of anorexia nervosa: an overview of universal issues and contextual challenges

    PubMed Central

    2013-01-01

    Aim Anorexia Nervosa (AN) is a complex and clinically challenging syndrome. Intended for specialist audiences, this narrative review aims to summarise the available literature related to assessment in the adult patient context, synthesising both research evidence and clinical consensus guidelines. Method We provide a review of the available literature on specialist assessment of AN focusing on common trajectories into assessment, obstacles accessing assessment, common presenting issues and barriers to the assessment process, the necessary scope of assessment, and tools and techniques. It describes the further step of synthesising assessment information in ways that can inform resultant care plans. Results In addition to assessment of core behaviours and diagnostic skills, considerations for the expert assessor include the functions of primary care, systemic and personal barriers, knowledge of current assessment tools and research pertaining to comorbid pathology in AN, assessing severity of illness, role of family at assessment, as well as medical, nutritional and compulsory elements of assessment. Conclusion Comprehensive assessment of AN in the current healthcare context still remains largely the remit of the specialist ED clinician. Assessment should remain an on-going process, paying particular attention to available empirical evidence, thereby reducing the gap between research and practice. PMID:24999408

  16. New ground-based lidar enables volcanic CO2 flux measurements.

    PubMed

    Aiuppa, Alessandro; Fiorani, Luca; Santoro, Simone; Parracino, Stefano; Nuvoli, Marcello; Chiodini, Giovanni; Minopoli, Carmine; Tamburello, Giancarlo

    2015-09-01

    There have been substantial advances in the ability to monitor the activity of hazardous volcanoes in recent decades. However, obtaining early warning of eruptions remains challenging, because the patterns and consequences of volcanic unrests are both complex and nonlinear. Measuring volcanic gases has long been a key aspect of volcano monitoring since these mobile fluids should reach the surface long before the magma. There has been considerable progress in methods for remote and in-situ gas sensing, but measuring the flux of volcanic CO2-the most reliable gas precursor to an eruption-has remained a challenge. Here we report on the first direct quantitative measurements of the volcanic CO2 flux using a newly designed differential absorption lidar (DIAL), which were performed at the restless Campi Flegrei volcano. We show that DIAL makes it possible to remotely obtain volcanic CO2 flux time series with a high temporal resolution (tens of minutes) and accuracy (<30%). The ability of this lidar to remotely sense volcanic CO2 represents a major step forward in volcano monitoring, and will contribute improved volcanic CO2 flux inventories. Our results also demonstrate the unusually strong degassing behavior of Campi Flegrei fumaroles in the current ongoing state of unrest.

  17. Linking chlorophyll a fluorescence to photosynthesis for remote sensing applications: mechanisms and challenges.

    PubMed

    Porcar-Castell, Albert; Tyystjärvi, Esa; Atherton, Jon; van der Tol, Christiaan; Flexas, Jaume; Pfündel, Erhard E; Moreno, Jose; Frankenberg, Christian; Berry, Joseph A

    2014-08-01

    Chlorophyll a fluorescence (ChlF) has been used for decades to study the organization, functioning, and physiology of photosynthesis at the leaf and subcellular levels. ChlF is now measurable from remote sensing platforms. This provides a new optical means to track photosynthesis and gross primary productivity of terrestrial ecosystems. Importantly, the spatiotemporal and methodological context of the new applications is dramatically different compared with most of the available ChlF literature, which raises a number of important considerations. Although we have a good mechanistic understanding of the processes that control the ChlF signal over the short term, the seasonal link between ChlF and photosynthesis remains obscure. Additionally, while the current understanding of in vivo ChlF is based on pulse amplitude-modulated (PAM) measurements, remote sensing applications are based on the measurement of the passive solar-induced chlorophyll fluorescence (SIF), which entails important differences and new challenges that remain to be solved. In this review we introduce and revisit the physical, physiological, and methodological factors that control the leaf-level ChlF signal in the context of the new remote sensing applications. Specifically, we present the basis of photosynthetic acclimation and its optical signals, we introduce the physical and physiological basis of ChlF from the molecular to the leaf level and beyond, and we introduce and compare PAM and SIF methodology. Finally, we evaluate and identify the challenges that still remain to be answered in order to consolidate our mechanistic understanding of the remotely sensed SIF signal. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Complex metal borohydrides: multifunctional materials for energy storage and conversion

    NASA Astrophysics Data System (ADS)

    Mohtadi, Rana; Remhof, Arndt; Jena, Puru

    2016-09-01

    With the limited supply of fossil fuels and their adverse effect on the climate and the environment, it has become a global priority to seek alternate sources of energy that are clean, abundant, and sustainable. While sources such as solar, wind, and hydrogen can meet the world’s energy demand, considerable challenges remain to find materials that can store and/or convert energy efficiently. This topical review focuses on one such class of materials, namely, multi-functional complex metal borohydrides that not only have the ability to store sufficient amount of hydrogen to meet the needs of the transportation industry, but also can be used for a new generation of metal ion batteries and solar cells. We discuss the material challenges in all these areas and review the progress that has been made to address them, the issues that still need to be resolved and the outlook for the future.

  19. 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.

  20. Functional imaging and the cerebellum: recent developments and challenges. Editorial.

    PubMed

    Habas, Christophe

    2012-06-01

    Recent neuroimaging developments allow a better in vivo characterization of the structural and functional connectivity of the human cerebellum. Ultrahigh fields, which considerably increase spatial resolution, enable to visualize deep cerebellar nuclei and cerebello-cortical sublayers. Tractography reconstructs afferent and efferent pathway of the cerebellum. Resting-state functional connectivity individualizes the prewired, parallel close-looped sensorimotor, cognitive, and affective networks passing through the cerebellum. These results are un agreement with activation maps obtained during stimulation functional neuroimaging or inferred from neurological deficits due to cerebellar lesions. Therefore, neuroimaging supports the hypothesis that cerebellum constitutes a general modulator involved in optimizing mental performance and computing internal models. However, the great challenges will remain to unravel: (1) the functional role of red and bulbar olivary nuclei, (2) the information processing in the cerebellar microcircuitry, and (3) the abstract computation performed by the cerebellum and shared by sensorimotor, cognitive, and affective domains.

  1. From anatomical 'competence' to complex capability. The views and experiences of UK tutors on how we should teach anatomy to medical students.

    PubMed

    Regan de Bere, Sam; Mattick, Karen

    2010-10-01

    Developments in clinical education have recently challenged the identity of anatomy teaching and learning, leading to high profile debate over the potential implications for the competence levels of new doctors. However, the emphasis remains on methods of teaching, rather than a review of what well-rounded anatomical learning actually entails, and how teaching can address contemporary learning needs. This paper identifies and addresses some of these issues, drawing on expert views captured in qualitative research with anatomy tutors at twenty different medical schools in the UK. Three main themes emerging from our analysis are described: anatomy as a subject matter, the challenges of teaching or learning anatomy, and the use of teaching methods. We also detail how inductive analysis generated new hypotheses worthy of further consideration. These fall into two key categories: (1) improving anatomy curriculum design and (2) advancing anatomy education research.

  2. Complex metal borohydrides: multifunctional materials for energy storage and conversion.

    PubMed

    Mohtadi, Rana; Remhof, Arndt; Jena, Puru

    2016-09-07

    With the limited supply of fossil fuels and their adverse effect on the climate and the environment, it has become a global priority to seek alternate sources of energy that are clean, abundant, and sustainable. While sources such as solar, wind, and hydrogen can meet the world's energy demand, considerable challenges remain to find materials that can store and/or convert energy efficiently. This topical review focuses on one such class of materials, namely, multi-functional complex metal borohydrides that not only have the ability to store sufficient amount of hydrogen to meet the needs of the transportation industry, but also can be used for a new generation of metal ion batteries and solar cells. We discuss the material challenges in all these areas and review the progress that has been made to address them, the issues that still need to be resolved and the outlook for the future.

  3. The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

    PubMed Central

    Butler, David L.; Goldstein, Steven A.; Guo, X. Edward; Kamm, Roger; Laurencin, Cato T.; McIntire, Larry V.; Mow, Van C.; Nerem, Robert M.; Sah, Robert L.; Soslowsky, Louis J.; Spilker, Robert L.; Tranquillo, Robert T.

    2009-01-01

    Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges. PMID:19583462

  4. Dissolution DNP for in vivo preclinical studies

    NASA Astrophysics Data System (ADS)

    Comment, Arnaud

    2016-03-01

    The tremendous polarization enhancement afforded by dissolution dynamic nuclear polarization (DNP) can be taken advantage of to perform preclinical in vivo molecular and metabolic imaging. Following the injection of molecules that are hyperpolarized via dissolution DNP, real-time measurements of their biodistribution and metabolic conversion can be recorded. This technology therefore provides a unique and invaluable tool for probing cellular metabolism in vivo in animal models in a noninvasive manner. It gives the opportunity to follow and evaluate disease progression and treatment response without requiring ex vivo destructive tissue assays. Although its considerable potential has now been widely recognized, hyperpolarized magnetic resonance by dissolution DNP remains a challenging method to implement for routine in vivo preclinical measurements. The aim of this article is to provide an overview of the current state-of-the-art technology for preclinical applications and the challenges that need to be addressed to promote it and allow its wider dissemination in the near future.

  5. National Immunization Program: Computerized System as a tool for new challenges

    PubMed Central

    Sato, Ana Paula Sayuri

    2015-01-01

    The scope and coverage of the Brazilian Immunization Program can be compared with those in developed countries because it provides a large number of vaccines and has a considerable coverage. The increasing complexity of the program brings challenges regarding its development, high coverage levels, access equality, and safety. The Immunization Information System, with nominal data, is an innovative tool that can more accurately monitor these indicators and allows the evaluation of the impact of new vaccination strategies. The main difficulties for such a system are in its implementation process, training of professionals, mastering its use, its constant maintenance needs and ensuring the information contained remain confidential. Therefore, encouraging the development of this tool should be part of public health policies and should also be involved in the three spheres of government as well as the public and private vaccination services. PMID:26176746

  6. Annual Research Review: Threats to the validity of child psychiatry and psychology.

    PubMed

    Rutter, Michael; Pickles, Andrew

    2016-03-01

    Suggestions have been made that many claims concern false-positive findings in the field of child psychology and psychiatry. The literature was searched for concepts and findings on the validity of child psychiatry and psychology. Substantial progress has been made in some, but not all, areas and considerable challenges remain in all. The two major threats to validity concern the inability to examine brain tissues in life and the evidence that there is a high overlap among disorders. We emphasize the need to follow published guidelines on preplanned analyses and we note the dangers associated with unregulated flexibility in data analysis. We note the very important clinical and developmental findings that have been ignored, perhaps partly because of an excessive focus on technologies. Nevertheless, we are positive about both the accomplishments and the ways in which challenges are being met. © 2015 Association for Child and Adolescent Mental Health.

  7. Regulatory challenges in developing long-acting antiretrovirals for treatment and prevention of HIV infection.

    PubMed

    Arya, Vikram; Au, Stanley; Belew, Yodit; Miele, Peter; Struble, Kimberly

    2015-07-01

    To outline some of the regulatory challenges inherent to the development of long-acting antiretrovirals (ARVs) for the treatment or prevention of HIV infection. Despite advances in drug development that have reduced ARV dosing to once daily, suboptimal drug adherence remains an obstacle to successful HIV treatment. Further, large randomized trials of once daily oral ARVs for preexposure prophylaxis (PrEP) have shown that drug adherence correlates strongly with prophylactic effect and study outcomes. Thus, the prospect of developing long-acting ARVs, which may mitigate drug adherence issues, has attracted considerable attention lately. Because of their pharmacokinetic properties, the development of long-acting ARVs can present novel regulatory challenges. Chief among them is determining the appropriate dosing regimen, the need for an oral lead-in, and whether existing data with an approved oral agent, if available, can be leveraged for a treatment or prevention indication. For PrEP, because validated biomarkers are lacking, additional nonclinical studies and evaluation of tissue concentrations in multiple compartments may be necessary to identify optimal dosages. Study design and choice of controls for registrational trials of new long-acting PrEP agents might also prove challenging following the availability of an oral PrEP drug.

  8. Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations.

    PubMed

    Cournia, Zoe; Allen, Bryce; Sherman, Woody

    2017-12-26

    Accurate in silico prediction of protein-ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational methods have historically failed to deliver value in real-world drug discovery applications due to a variety of scientific, technical, and practical challenges. Recently, a family of approaches commonly referred to as relative binding free energy (RBFE) calculations, which rely on physics-based molecular simulations and statistical mechanics, have shown promise in reliably generating accurate predictions in the context of drug discovery projects. This advance arises from accumulating developments in the underlying scientific methods (decades of research on force fields and sampling algorithms) coupled with vast increases in computational resources (graphics processing units and cloud infrastructures). Mounting evidence from retrospective validation studies, blind challenge predictions, and prospective applications suggests that RBFE simulations can now predict the affinity differences for congeneric ligands with sufficient accuracy and throughput to deliver considerable value in hit-to-lead and lead optimization efforts. Here, we present an overview of current RBFE implementations, highlighting recent advances and remaining challenges, along with examples that emphasize practical considerations for obtaining reliable RBFE results. We focus specifically on relative binding free energies because the calculations are less computationally intensive than absolute binding free energy (ABFE) calculations and map directly onto the hit-to-lead and lead optimization processes, where the prediction of relative binding energies between a reference molecule and new ideas (virtual molecules) can be used to prioritize molecules for synthesis. We describe the critical aspects of running RBFE calculations, from both theoretical and applied perspectives, using a combination of retrospective literature examples and prospective studies from drug discovery projects. This work is intended to provide a contemporary overview of the scientific, technical, and practical issues associated with running relative binding free energy simulations, with a focus on real-world drug discovery applications. We offer guidelines for improving the accuracy of RBFE simulations, especially for challenging cases, and emphasize unresolved issues that could be improved by further research in the field.

  9. Oxide nanomaterials: synthetic developments, mechanistic studies, and technological innovations.

    PubMed

    Patzke, Greta R; Zhou, Ying; Kontic, Roman; Conrad, Franziska

    2011-01-24

    Oxide nanomaterials are indispensable for nanotechnological innovations, because they combine an infinite variety of structural motifs and properties with manifold morphological features. Given that new oxide materials are almost reported on a daily basis, considerable synthetic and technological work remains to be done to fully exploit this ever increasing family of compounds for innovative nano-applications. This calls for reliable and scalable preparative approaches to oxide nanomaterials and their development remains a challenge for many complex nanostructured oxides. Oxide nanomaterials with special physicochemical features and unusual morphologies are still difficult to access by classic synthetic pathways. The limitless options for creating nano-oxide building blocks open up new technological perspectives with the potential to revolutionize areas ranging from data processing to biocatalysis. Oxide nanotechnology of the 21st century thus needs a strong interplay of preparative creativity, analytical skills, and new ideas for synergistic implementations. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Conservation of wading birds

    USGS Publications Warehouse

    Kushlan, J.A.

    1996-01-01

    The conservation and management of wading birds has received considerable attention over the past twenty years, through research, population monitoring, habitat protection, and through activities of specialist groups devoted to all three groups, the herons, ibises and allies, and flamingos. While populations are best known in North America, greatest advances in knowledge may have come in Australasia. The status of most species and many populations is now sufficiently known to allow assessment of risk. Conservation and management techniques allow creation of global and regional action plans for conservation of many species. Global action plans are being developed, but few regional plans have been undertaken. Management of nesting sites is now particularly well appreciated. Although known in broad stroke, much remains to be learned about managing feeding habitat. Problems related to disturbance, conflict with humans, habitat loss, contaminants and other environmental stresses remain for some species and many populations. New challenges lie in creating conservation action that account for genetic stocks.

  11. The common cold: potential for future prevention or cure.

    PubMed

    Passioti, Maria; Maggina, Paraskevi; Megremis, Spyridon; Papadopoulos, Nikolaos G

    2014-02-01

    The common cold is the most frequent, although generally mild, human disease. Human Rhinoviruses are the prevalent causative agents, but other viruses are also implicated. Being so common, viral colds, have significant implications on public health and quality of life, but may also be life-threatening for vulnerable groups of patients. Specific diagnosis and treatment of the common cold still remain unmet needs. Molecular diagnostic techniques allow specific detection of known pathogens as well as the identification of newly emerging viruses. Although a number of medications or natural treatments have been shown to have some effect, either on the number or on the severity of common colds, no single agent is considerably effective. Virus-specific management remains in most cases a challenging potential as many factors have to be taken into account, including the diversity of the viral genomes, the heterogeneity of affected individuals, as well as the complexity of this long standing host-virus relationship.

  12. CT, MRI and PET imaging in peritoneal malignancy

    PubMed Central

    Sahdev, Anju; Reznek, Rodney H.

    2011-01-01

    Abstract Imaging plays a vital role in the evaluation of patients with suspected or proven peritoneal malignancy. Nevertheless, despite significant advances in imaging technology and protocols, assessment of peritoneal pathology remains challenging. The combination of complex peritoneal anatomy, an extensive surface area that may host tumour deposits and the considerable overlap of imaging appearances of various peritoneal diseases often makes interpretation difficult. Contrast-enhanced multidetector computed tomography (MDCT) remains the most versatile tool in the imaging of peritoneal malignancy. However, conventional and emerging magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT techniques offer significant advantages over MDCT in detection and surveillance. This article reviews established and new techniques in CT, MRI and PET imaging in both primary and secondary peritoneal malignancies and provides an overview of peritoneal anatomy, function and modes of disease dissemination with illustration of common sites and imaging features of peritoneal malignancy. PMID:21865109

  13. Strengthening laboratory systems in resource-limited settings.

    PubMed

    Olmsted, Stuart S; Moore, Melinda; Meili, Robin C; Duber, Herbert C; Wasserman, Jeffrey; Sama, Preethi; Mundell, Ben; Hilborne, Lee H

    2010-09-01

    Considerable resources have been invested in recent years to improve laboratory systems in resource-limited settings. We reviewed published reports, interviewed major donor organizations, and conducted case studies of laboratory systems in 3 countries to assess how countries and donors have worked together to improve laboratory services. While infrastructure and the provision of services have seen improvement, important opportunities remain for further advancement. Implementation of national laboratory plans is inconsistent, human resources are limited, and quality laboratory services rarely extend to lower tier laboratories (eg, health clinics, district hospitals). Coordination within, between, and among governments and donor organizations is also frequently problematic. Laboratory standardization and quality control are improving but remain challenging, making accreditation a difficult goal. Host country governments and their external funding partners should coordinate their efforts effectively around a host country's own national laboratory plan to advance sustainable capacity development throughout a country's laboratory system.

  14. Management of a multinational mass fatality incident in Kaprun, Austria: a forensic medical perspective.

    PubMed

    Labovich, Marc H; Duke, Jim B; Ingwersen, Kathleen M; Roath, David B

    2003-01-01

    The Armed Forces Regional Medical Examiner in Europe is responsible for medico-legal death investigations for the U.S. military in 89 countries in Europe, Southwest Asia, and Africa. The Disaster Mortuary Affairs Response Team (DMART) is a rapidly deployable, experienced, multidisciplinary team patterned after the regional U.S. civilian Disaster Mortuary Response Teams. One of the first major challenges since the DMART's inception occurred on November 11, 2000. A fire in a funicular servicing a ski resort claimed 155 victims in a mountain tunnel in Kaprun, Austria. The DMART deployed to assist the Austrian authorities in the rapid recovery, examination, identification, and return of the remains. The DMART's considerable forensic expertise and inherent spirit of cooperation were instrumental in the successful management of the disaster, resulting in the positive identification and release of all 155 remains within 2 weeks of the incident.

  15. Breaking barriers in the genomics and pharmacogenetics of drug addiction

    PubMed Central

    Ho, MK; Goldman, D; Heinz, A; Kaprio, J; Kreek, MJ; Li, MD; Munafò, MR; Tyndale, RF

    2013-01-01

    Drug addictions remain a substantial health issue, with limited treatment options currently available. Despite considerable advances in the understanding of our genetic architecture, the genetic underpinning of complex disorders remains elusive. Numerous candidate genes have been implicated in the etiology and response to treatment for different addictions based on our current understanding of the neurobiology. Genome-wide association studies have also provided novel targets. However, replication of these studies is often lacking which complicates interpretation; this will improve as issues such as phenotypic characterization, the apparent “missing heritability”, the identification of functional variants, and possible gene-environment interactions are addressed. In addition, there is growing evidence that genetic information can be useful for refining the choice of addiction treatment. As genetic testing becomes more common in the practice of medicine, a variety of ethical and practical challenges, some of which are unique to drug addiction, will also need to be considered. PMID:20981002

  16. A review on the Scorpaena plumieri fish venom and its bioactive compounds.

    PubMed

    Campos, Fabiana V; Menezes, Thiago N; Malacarne, Pedro F; Costa, Fábio L S; Naumann, Gustavo B; Gomes, Helena L; Figueiredo, Suely G

    2016-01-01

    The most poisonous fish species found along the Brazilian coast is the spotted scorpionfish Scorpaena plumieri . Though hardly ever life-threatening to humans, envenomation by S. plumieri can be quite hazardous, provoking extreme pain and imposing significant socioeconomic costs, as the victims may require days to weeks to recover from their injuries. In this review we will walk the reader through the biological features that distinguish this species as well as the current epidemiological knowledge related to the envenomation and its consequences. But above all, we will discuss the challenges involved in the biochemical characterization of the S. plumieri venom and its compounds, focusing then on the successful isolation and pharmacological analysis of some of the bioactive molecules responsible for the effects observed upon envenomation as well as on experimental models. Despite the achievement of considerable progress, much remains to be done, particularly in relation to the non-proteinaceous components of the venom. Therefore, further studies are necessary in order to provide a more complete picture of the venom's chemical composition and physiological effects. Given that fish venoms remain considerably less studied when compared to terrestrial venoms, the exploration of their full potential opens a myriad of possibilities for the development of new drug leads and tools for elucidating the complex physiological processes.

  17. Childhood glaucoma surgery in the 21st Century

    PubMed Central

    Papadopoulos, M; Edmunds, B; Fenerty, C; Khaw, P T

    2014-01-01

    Most children with glaucoma will require surgery in their lifetime, often in their childhood years. The surgical management of childhood glaucoma is however challenging, largely because of its greater potential for failure and complications as compared with surgery in adults. The available surgical repertoire for childhood glaucoma has remained relatively unchanged for many years with most progress owing to modifications to existing surgery. Although the surgical approach to childhood glaucoma varies around the world, angle surgery remains the preferred initial surgery for primary congenital glaucoma and a major advance has been the concept of incising the whole of the angle (circumferential trabeculotomy). Simple modifications to the trabeculectomy technique have been shown to considerably minimise complications. Glaucoma drainage devices maintain a vital role for certain types of glaucoma including those refractory to other surgery. Cyclodestruction continues to have a role mainly for patients following failed drainage/filtering surgery. Although the prognosis for childhood glaucoma has improved significantly since the introduction of angle surgery, there is still considerable progress to be made to ensure a sighted lifetime for children with glaucoma all over the world. Collaborative approaches to researching and delivering this care are required, and this paper highlights the need for more high-quality prospective surgical trials in the management of the childhood glaucoma. PMID:24924446

  18. Influenza-Omics and the Host Response: Recent Advances and Future Prospects

    PubMed Central

    Powell, Joshua D.; Waters, Katrina M.

    2017-01-01

    Influenza A viruses (IAV) continually evolve and have the capacity to cause global pandemics. Because IAV represents an ongoing threat, identifying novel therapies and host innate immune factors that contribute to IAV pathogenesis is of considerable interest. This review summarizes the relevant literature as it relates to global host responses to influenza infection at both the proteome and transcriptome level. The various-omics infection systems that include but are not limited to ferrets, mice, pigs, and even the controlled infection of humans are reviewed. Discussion focuses on recent advances, remaining challenges, and knowledge gaps as it relates to influenza-omics infection outcomes. PMID:28604586

  19. Complex Genetics and the Etiology of Human Congenital Heart Disease

    PubMed Central

    Gelb, Bruce D.; Chung, Wendy K.

    2014-01-01

    Congenital heart disease (CHD) is the most common birth defect. Despite considerable advances in care, CHD remains a major contributor to newborn mortality and is associated with substantial morbidities and premature death. Genetic abnormalities appear to be the primary cause of CHD, but identifying precise defects has proven challenging, principally because CHD is a complex genetic trait. Mainly because of recent advances in genomic technology such as next-generation DNA sequencing, scientists have begun to identify the genetic variants underlying CHD. In this article, the roles of modifier genes, de novo mutations, copy number variants, common variants, and noncoding mutations in the pathogenesis of CHD are reviewed. PMID:24985128

  20. Sepsis in Older Adults.

    PubMed

    Rowe, Theresa A; McKoy, June M

    2017-12-01

    Sepsis disproportionally affects older adults with more than 60% of sepsis diagnoses attributed to adults aged 65 years and older. Identifying, diagnosing, and treating sepsis in older individuals remain a challenge for clinicians, and few studies focus specifically on older adults with multiple medical comorbidities. Principles guiding management of sepsis for older adults are generally the same as in younger adults; however, unique considerations particularly pertinent to the care older adults include antimicrobial selection and dosing, delirium management, and goals of care discussions. Other factors, such as medical comorbidities, cognitive impairment, and functional status, impact outcomes more than age alone. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Influenza-Omics and the Host Response: Recent Advances and Future Prospects

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

    Powell, Joshua D.; Waters, Katrina M.

    Influenza A viruses (IAV) continually evolve and have the capacity to cause global pandemics. Because IAV represents an ongoing threat, identifying novel therapies and host innate immune factors that contribute to IAV pathogenesis is of considerable interest. This review summarizes the relevant literature as it relates to global host responses to influenza infection at both the proteome and transcriptome level. Here, the various –omics infection systems that include but are not limited to ferrets, mice, pigs and even controlled infection of humans are reviewed. Discussion focuses on recent advances, remaining challenges, and knowledge gaps as it relates to influenza-omics infectionmore » outcomes.« less

  2. Advances in treating exposed fractures.

    PubMed

    Nogueira Giglio, Pedro; Fogaça Cristante, Alexandre; Ricardo Pécora, José; Partezani Helito, Camilo; Lei Munhoz Lima, Ana Lucia; Dos Santos Silva, Jorge

    2015-01-01

    The management of exposed fractures has been discussed since ancient times and remains of great interest to present-day orthopedics and traumatology. These injuries are still a challenge. Infection and nonunion are feared complications. Aspects of the diagnosis, classification and initial management are discussed here. Early administration of antibiotics, surgical cleaning and meticulous debridement are essential. The systemic conditions of patients with multiple trauma and the local conditions of the limb affected need to be taken into consideration. Early skeletal stabilization is necessary. Definitive fixation should be considered when possible and provisional fixation methods should be used when necessary. Early closure should be the aim, and flaps can be used for this purpose.

  3. Nano/Micro and Spectroscopic Approaches to Food Pathogen Detection

    NASA Astrophysics Data System (ADS)

    Cho, Il-Hoon; Radadia, Adarsh D.; Farrokhzad, Khashayar; Ximenes, Eduardo; Bae, Euiwon; Singh, Atul K.; Oliver, Haley; Ladisch, Michael; Bhunia, Arun; Applegate, Bruce; Mauer, Lisa; Bashir, Rashid; Irudayaraj, Joseph

    2014-06-01

    Despite continuing research efforts, timely and simple pathogen detection with a high degree of sensitivity and specificity remains an elusive goal. Given the recent explosion of sensor technologies, significant strides have been made in addressing the various nuances of this important global challenge that affects not only the food industry but also human health. In this review, we provide a summary of the various ongoing efforts in pathogen detection and sample preparation in areas related to Fourier transform infrared and Raman spectroscopy, light scattering, phage display, micro/nanodevices, and nanoparticle biosensors. We also discuss the advantages and potential limitations of the detection methods and suggest next steps for further consideration.

  4. Challenges ahead on property front.

    PubMed

    Lea, Graham

    2013-03-01

    As the dissolution of the PCTs draws closer, and the assets and buildings formerly owned by them transfer, at the start of April, to the new NHS Property Services Company (see also HEJ - February 2013), there remains a considerable amount to be done by those involved in the real estate aspects of the NHS reorganisation. So says Graham Lea, a partner, and the national head of the company's real estate team, at law firm, Hempsons. He explains that, for NHS estates personnel, occupiers, developers, and investors, there are still a number of key issues to clarify, not least how property development decisions will be taken, and the prospects for investment in an ageing estate.

  5. Sleep-Disordered Breathing and Arrhythmia in Heart Failure Patients.

    PubMed

    Fox, Henrik; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf

    2017-06-01

    Heart failure (HF) treatment remains complex and challenging, with current recommendations aiming at consideration and treatment of comorbidities in patients with HF. Sleep-disordered breathing (SDB) and arrhythmia come into play, as both are associated with quality of life deterioration, and morbidity and mortality increase in patients with HF. Interactions of these diseases are versatile and may appear intransparent in daily practice. Nevertheless, because of their importance for patients' condition and prognosis, SDB and arrhythmia individually, but also through interaction on one another, necessitate attention, following the fact that treatment is requested and desired considering latest research findings and outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Influenza-Omics and the Host Response: Recent Advances and Future Prospects

    DOE PAGES

    Powell, Joshua D.; Waters, Katrina M.

    2017-06-10

    Influenza A viruses (IAV) continually evolve and have the capacity to cause global pandemics. Because IAV represents an ongoing threat, identifying novel therapies and host innate immune factors that contribute to IAV pathogenesis is of considerable interest. This review summarizes the relevant literature as it relates to global host responses to influenza infection at both the proteome and transcriptome level. Here, the various –omics infection systems that include but are not limited to ferrets, mice, pigs and even controlled infection of humans are reviewed. Discussion focuses on recent advances, remaining challenges, and knowledge gaps as it relates to influenza-omics infectionmore » outcomes.« less

  7. Time to Consider Moving Beyond Exclusive Breastfeeding in Southern Africa

    PubMed Central

    Wojcicki, Janet M.

    2017-01-01

    While there have been considerable advances in the reduction of mother to child transmission of HIV (MTCT) in sub-Saharan Africa with the advance of anti-retroviral therapies (ART), there remain challenges in the late postpartum period.  Structural issues including food insecurity and stigma make better maternal ART adherence and exclusive breastfeeding unreachable for some women. There are no other scientifically researched feeding options as there have been few studies on different types of mixed feeding practices and risk of HIV infection. Additional studies are warranted to assess detailed feeding practices in HIV exposed infants in relation to clinical outcomes. PMID:28125026

  8. Nucleic acids-based tools for ballast water surveillance, monitoring, and research

    NASA Astrophysics Data System (ADS)

    Darling, John A.; Frederick, Raymond M.

    2018-03-01

    Understanding the risks of biological invasion posed by ballast water-whether in the context of compliance testing, routine monitoring, or basic research-is fundamentally an exercise in biodiversity assessment, and as such should take advantage of the best tools available for tackling that problem. The past several decades have seen growing application of genetic methods for the study of biodiversity, driven in large part by dramatic technological advances in nucleic acids analysis. Monitoring approaches based on such methods have the potential to increase dramatically sampling throughput for biodiversity assessments, and to improve on the sensitivity, specificity, and taxonomic accuracy of traditional approaches. The application of targeted detection tools (largely focused on PCR but increasingly incorporating novel probe-based methodologies) has led to a paradigm shift in rare species monitoring, and such tools have already been applied for early detection in the context of ballast water surveillance. Rapid improvements in community profiling approaches based on high throughput sequencing (HTS) could similarly impact broader efforts to catalogue biodiversity present in ballast tanks, and could provide novel opportunities to better understand the risks of biotic exchange posed by ballast water transport-and the effectiveness of attempts to mitigate those risks. These various approaches still face considerable challenges to effective implementation, depending on particular management or research needs. Compliance testing, for instance, remains dependent on accurate quantification of viable target organisms; while tools based on RNA detection show promise in this context, the demands of such testing require considerable additional investment in methods development. In general surveillance and research contexts, both targeted and community-based approaches are still limited by various factors: quantification remains a challenge (especially for taxa in larger size classes), gaps in nucleic acids reference databases are still considerable, uncertainties in taxonomic assignment methods persist, and many applications have not yet matured sufficiently to offer standardized methods capable of meeting rigorous quality assurance standards. Nevertheless, the potential value of these tools, their growing utilization in biodiversity monitoring, and the rapid methodological advances over the past decade all suggest that they should be seriously considered for inclusion in the ballast water surveillance toolkit.

  9. Design control considerations for biologic-device combination products.

    PubMed

    Anderson, Dave; Liu, Roger; Anand Subramony, J; Cammack, Jon

    2017-03-01

    Combination products are therapeutic and diagnostic medical products that combine drugs, devices, and/or biological products with one another. Historically, biologics development involved identifying efficacious doses administered to patients intravenously or perhaps by a syringe. Until fairly recently, there has been limited focus on developing an accompanying medical device, such as a prefilled syringe or auto-injector, to enable easy and more efficient delivery. For the last several years, and looking forward, where there may be little to distinguish biologics medicines with relatively similar efficacy profiles, the biotechnology market is beginning to differentiate products by patient-focused, biologic-device based combination products. As innovative as biologic-device combination products are, they can pose considerable development, regulatory, and commercialization challenges due to unique physicochemical properties and special clinical considerations (e.g., dosing volumes, frequency, co-medications, etc.) of the biologic medicine. A biologic-device combination product is a marriage between two partners with "cultural differences," so to speak. There are clear differences in the development, review, and commercialization processes of the biologic and the device. When these two cultures come together in a combination product, developers and reviewers must find ways to address the design controls and risk management processes of both the biologic and device, and knit them into a single entity with supporting product approval documentation. Moreover, digital medicine and connected health trends are pushing the boundaries of combination product development and regulations even further. Despite an admirable cooperation between industry and FDA in recent years, unique product configurations and design features have resulted in review challenges. These challenges have prompted agency reviewers to modernize consultation processes, while at the same time, promoting development of innovative, safe and effective combination products. It remains the manufacturer's responsibility to comply with the relevant requirements and regulations, and develop good business practices that clearly describe how these practices comply with FDA's final rule (21 CFR Part 4) and aligns with the company's already established quality system. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Knowledge management and informatics considerations for comparative effectiveness research: a case-driven exploration.

    PubMed

    Embi, Peter J; Hebert, Courtney; Gordillo, Gayle; Kelleher, Kelly; Payne, Philip R O

    2013-08-01

    As clinical data are increasingly collected and stored electronically, their potential use for comparative effectiveness research (CER) grows. Despite this promise, challenges face those wishing to leverage such data. In this paper we aim to enumerate some of the knowledge management and informatics issues common to such data reuse. After reviewing the current state of knowledge regarding biomedical informatics challenges and best practices related to CER, we then present 2 research projects at our institution. We analyze these and highlight several common themes and challenges related to the conduct of CER studies. Finally, we represent these emergent themes. The informatics challenges commonly encountered by those conducting CER studies include issues related to data information and knowledge management (eg, data reuse, data preparation) as well as those related to people and organizational issues (eg, sociotechnical factors and organizational factors). Examples of these are described in further detail and a formal framework for describing these findings is presented. Significant challenges face researchers attempting to use often diverse and heterogeneous datasets for CER. These challenges must be understood in order to be dealt with successfully and can often be overcome with the appropriate use of informatics best practices. Many research and policy questions remain to be answered in order to realize the full potential of the increasingly electronic clinical data available for such research.

  11. Ethical Issues and Practical Challenges in Suicide Research.

    PubMed

    Hom, Melanie A; Podlogar, Matthew C; Stanley, Ian H; Joiner, Thomas E

    2017-03-01

    Research with human subjects represents a critical avenue for suicide prevention efforts; however, such research is not without its ethical and practical challenges. Specifically, given the nature of research with individuals at elevated risk for suicide (e.g., increased concerns regarding participant safety, adverse events, liability, difficulties often arise during the institutional review board (IRB) evaluation and approval process. This paper aims to discuss IRB-related issues associated with suicide prevention research, including researcher and IRB panel member responsibilities, suicide risk assessment and management ethics and procedures, informed consent considerations, preparation of study protocols, and education and training. Points to consider and components to potentially include in an IRB application for suicide-related research are additionally provided. Literature relevant to ethics in suicide research and suicide risk assessment and management was reviewed and synthesized. Suicide research can be conducted in accordance with ethical principles while also furthering the science of suicide prevention. Despite the challenging nature of suicide prevention research, empirically informed solutions exist to address difficulties that may emerge in interfacing with IRBs. There remain areas for improvement in the IRB approval process that warrant further investigation and work.

  12. Positioning challenges in reconfigurable semi-autonomous robotic NDE inspection

    NASA Astrophysics Data System (ADS)

    Pierce, S. Gareth; Dobie, Gordon; Summan, Rahul; Mackenzie, Liam; Hensman, James; Worden, Keith; Hayward, Gordon

    2010-03-01

    This paper describes work conducted into mobile, wireless, semi-autonomous NDE inspection robots developed at The University of Strathclyde as part of the UK Research Centre for Non Destructive Evaluation (RCNDE). The inspection vehicles can incorporate a number of different NDE payloads including ultrasonic, eddy current, visual and magnetic based payloads, and have been developed to try and improve NDE inspection techniques in challenging inspection areas (for example oil, gas, and nuclear structures). A significant research challenge remains in the accurate positioning and guidance of such vehicles for real inspection tasks. Employing both relative and absolute position measurements, we discuss a number of approaches to position estimation including Kalman and particle filtering. Using probabilistic approaches enables a common mathematical framework to be employed for both positioning and data fusion from different NDE sensors. In this fashion the uncertainties in both position and defect identification and classification can be dealt with using a consistent approach. A number of practical constraints and considerations to different precision positioning techniques are discussed, along with NDE applications and the potential for improved inspection capabilities by utilising the inherent reconfigurable capabilities of the inspection vehicles.

  13. Nanoparticle-based Therapies for Wound Biofilm Infection: Opportunities and Challenges

    PubMed Central

    Kim, Min-Ho

    2016-01-01

    Clinical data from human chronic wounds implicates biofilm formation with the onset of wound chronicity. Despite the development of novel antimicrobial agents, the cost and complexity of treating chronic wound infections associated with biofilms remain a serious challenge, which necessitates the development of new and alternative approaches for effective anti-biofilm treatment. Recent advancement in nanotechnology for developing a new class of nanoparticles that exhibit unique chemical and physical properties holds promise for the treatment of biofilm infections. Over the last decade, nanoparticle-based approaches against wound biofilm infection have been directed toward developing nanoparticles with intrinsic antimicrobial properties, utilizing nanoparticles for controlled antimicrobials delivery, and applying nanoparticles for antibacterial hyperthermia therapy. In addition, a strategy to functionalize nanoparticles towards enhanced penetration through the biofilm matrix has been receiving considerable interest recently by means of achieving an efficient targeting to the bacterial cells within biofilm matrix. This review summarizes and highlights the recent development of these nanoparticle-based approaches as potential therapeutics for controlling wound biofilm infection, along with current challenges that need to be overcome for their successful clinical translation. PMID:26955044

  14. Hybrid governance of aquaculture: Opportunities and challenges.

    PubMed

    Vince, Joanna; Haward, Marcus

    2017-10-01

    The development of third party assessment and certification of fisheries and aquaculture has provided new forms of governance in sectors that were traditionally dominated by state based regulation. Emerging market based approaches are driven by shareholder expectations as well as commitment to corporate social responsibility, whereas community engagement is increasingly centered on the questions of social license to operate. Third party assessment and certification links state, market and community into an interesting and challenging hybrid form of governance. While civil society organizations have long been active in pursuing sustainable and safe seafood production, the development of formal non-state based certification provides both opportunities and challenges, and opens up interesting debates over hybrid forms of governance. This paper explores these developments in coastal marine resources management, focusing on aquaculture and the development and operation of the Aquaculture Stewardship Council. It examines the case of salmonid aquaculture in Tasmania, Australia, now Australia's most valuable seafood industry, which remains the focus of considerable community debate over its siting, operation and environmental impact. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Navigating the challenges of digital health innovation: considerations and solutions in developing online and smartphone-application-based interventions for mental health disorders.

    PubMed

    Hill, Claire; Martin, Jennifer L; Thomson, Simon; Scott-Ram, Nick; Penfold, Hugh; Creswell, Cathy

    2017-08-01

    This article presents an analysis of challenges and considerations when developing digital mental health innovations. Recommendations include collaborative working between clinicians, researchers, industry and service users in order to successfully navigate challenges and to ensure e-therapies are engaging, acceptable, evidence based, scalable and sustainable. © The Royal College of Psychiatrists 2017.

  16. Algae as nutritional and functional food sources: revisiting our understanding.

    PubMed

    Wells, Mark L; Potin, Philippe; Craigie, James S; Raven, John A; Merchant, Sabeeha S; Helliwell, Katherine E; Smith, Alison G; Camire, Mary Ellen; Brawley, Susan H

    2017-01-01

    Global demand for macroalgal and microalgal foods is growing, and algae are increasingly being consumed for functional benefits beyond the traditional considerations of nutrition and health. There is substantial evidence for the health benefits of algal-derived food products, but there remain considerable challenges in quantifying these benefits, as well as possible adverse effects. First, there is a limited understanding of nutritional composition across algal species, geographical regions, and seasons, all of which can substantially affect their dietary value. The second issue is quantifying which fractions of algal foods are bioavailable to humans, and which factors influence how food constituents are released, ranging from food preparation through genetic differentiation in the gut microbiome. Third is understanding how algal nutritional and functional constituents interact in human metabolism. Superimposed considerations are the effects of harvesting, storage, and food processing techniques that can dramatically influence the potential nutritive value of algal-derived foods. We highlight this rapidly advancing area of algal science with a particular focus on the key research required to assess better the health benefits of an alga or algal product. There are rich opportunities for phycologists in this emerging field, requiring exciting new experimental and collaborative approaches.

  17. Sexually transmitted infections: challenges ahead.

    PubMed

    Unemo, Magnus; Bradshaw, Catriona S; Hocking, Jane S; de Vries, Henry J C; Francis, Suzanna C; Mabey, David; Marrazzo, Jeanne M; Sonder, Gerard J B; Schwebke, Jane R; Hoornenborg, Elske; Peeling, Rosanna W; Philip, Susan S; Low, Nicola; Fairley, Christopher K

    2017-08-01

    WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Fielding a current idea: exploring the public health impact of electromagnetic radiation.

    PubMed

    Genuis, Stephen J

    2008-02-01

    Several publications in the scientific literature have raised concern about the individual and public health impact of adverse non-ionizing radiation (a-NIR) from electromagnetic field (EMF) exposure emanating from certain power, electrical and wireless devices commonly found in the home, workplace, school and community. Despite the many challenges in establishing irrefutable scientific proof of harm and the various gaps in elucidating the precise mechanisms of harm, epidemiological analyses continue to suggest considerable potential for injury and affliction as a result of a-NIR exposure. As environmental health has not been emphasized in medical education, some clinicians are not fully aware of possible EMF-related health problems and, as a result, manifestations of a-NIR may remain misdiagnosed and ineffectually managed. It is important for physicians and public health officials to be aware of the fundamental science and clinical implications of EMF exposure. A review of the scientific literature relating to the link between electromagnetic radiation and human health, several public health recommendations, and four case histories are presented for consideration.

  19. Stabilization of Polar Nanoregions in Pb-free Ferroelectrics

    DOE PAGES

    Pramanick, A.; Dmowski, Wojciech; Egami, Takeshi; ...

    2018-05-18

    In this study, the formation of polar nanoregions through solid-solution additions is known to enhance significantly the functional properties of ferroelectric materials. Despite considerable progress in characterizing the microscopic behavior of polar nanoregions (PNR), understanding their real-space atomic structure and dynamics of their formation remains a considerable challenge. Here, using the method of dynamic pair distribution function, we provide direct insights into the role of solid-solution additions towards the stabilization of polar nanoregions in the Pb-free ferroelectric of Ba(Zr,Ti)O 3. It is shown that for an optimum level of substitution of Ti by larger Zr ions, the dynamics of atomicmore » displacements for ferroelectric polarization are slowed sufficiently below THz frequencies, which leads to increased local correlation among dipoles within PNRs. The dynamic pair distribution function technique demonstrates a unique capability to obtain insights into locally correlated atomic dynamics in disordered materials, including new Pb-free ferroelectrics, which is necessary to understand and control their functional properties.« less

  20. Stabilization of Polar Nanoregions in Pb-free Ferroelectrics

    NASA Astrophysics Data System (ADS)

    Pramanick, A.; Dmowski, W.; Egami, T.; Budisuharto, A. Setiadi; Weyland, F.; Novak, N.; Christianson, A. D.; Borreguero, J. M.; Abernathy, D. L.; Jørgensen, M. R. V.

    2018-05-01

    The formation of polar nanoregions through solid-solution additions is known to enhance significantly the functional properties of ferroelectric materials. Despite considerable progress in characterizing the microscopic behavior of polar nanoregions (PNR), understanding their real-space atomic structure and dynamics of their formation remains a considerable challenge. Here, using the method of dynamic pair distribution function, we provide direct insights into the role of solid-solution additions towards the stabilization of polar nanoregions in the Pb-free ferroelectric of Ba (Zr ,Ti )O3 . It is shown that for an optimum level of substitution of Ti by larger Zr ions, the dynamics of atomic displacements for ferroelectric polarization are slowed sufficiently below THz frequencies, which leads to increased local correlation among dipoles within PNRs. The dynamic pair distribution function technique demonstrates a unique capability to obtain insights into locally correlated atomic dynamics in disordered materials, including new Pb-free ferroelectrics, which is necessary to understand and control their functional properties.

  1. Donations After Circulatory Death in Liver Transplant

    PubMed Central

    Eren, Emre A.; Latchana, Nicholas; Beal, Eliza; Hayes, Don; Whitson, Bryan; Black, Sylvester M.

    2017-01-01

    The supply of liver grafts for treatment of end-stage liver disease continues to fall short of ongoing demands. Currently, most liver transplants originate from donations after brain death. Enhanced utilization of the present resources is prudent to address the needs of the population. Donation after circulatory or cardiac death is a mechanism whereby the availability of organs can be expanded. Donations after circulatory death pose unique challenges given their exposure to warm ischemia. Technical principles of donations after circulatory death procurement and pertinent studies investigating patient outcomes, graft outcomes, and complications are highlighted in this review. We also review associated risk factors to suggest potential avenues to achieve improved outcomes and reduced complications. Future considerations and alternative techniques of organ preservation are discussed, which may suggest novel strategies to enhance preservation and donor expansion through the use of marginal donors. Ultimately, without effective measures to bolster organ supply, donations after circulatory death should remain a consideration; however, an understanding of inherent risks and limitations is necessary. PMID:27733105

  2. Stabilization of Polar Nanoregions in Pb-free Ferroelectrics

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

    Pramanick, A.; Dmowski, Wojciech; Egami, Takeshi

    In this study, the formation of polar nanoregions through solid-solution additions is known to enhance significantly the functional properties of ferroelectric materials. Despite considerable progress in characterizing the microscopic behavior of polar nanoregions (PNR), understanding their real-space atomic structure and dynamics of their formation remains a considerable challenge. Here, using the method of dynamic pair distribution function, we provide direct insights into the role of solid-solution additions towards the stabilization of polar nanoregions in the Pb-free ferroelectric of Ba(Zr,Ti)O 3. It is shown that for an optimum level of substitution of Ti by larger Zr ions, the dynamics of atomicmore » displacements for ferroelectric polarization are slowed sufficiently below THz frequencies, which leads to increased local correlation among dipoles within PNRs. The dynamic pair distribution function technique demonstrates a unique capability to obtain insights into locally correlated atomic dynamics in disordered materials, including new Pb-free ferroelectrics, which is necessary to understand and control their functional properties.« less

  3. Donations After Circulatory Death in Liver Transplant.

    PubMed

    Eren, Emre A; Latchana, Nicholas; Beal, Eliza; Hayes, Don; Whitson, Bryan; Black, Sylvester M

    2016-10-01

    The supply of liver grafts for treatment of end-stage liver disease continues to fall short of ongoing demands. Currently, most liver transplants originate from donations after brain death. Enhanced utilization of the present resources is prudent to address the needs of the population. Donation after circulatory or cardiac death is a mechanism whereby the availability of organs can be expanded. Donations after circulatory death pose unique challenges given their exposure to warm ischemia. Technical principles of donations after circulatory death procurement and pertinent studies investigating patient outcomes, graft outcomes, and complications are highlighted in this review. We also review associated risk factors to suggest potential avenues to achieve improved outcomes and reduced complications. Future considerations and alternative techniques of organ preservation are discussed, which may suggest novel strategies to enhance preservation and donor expansion through the use of marginal donors. Ultimately, without effective measures to bolster organ supply, donations after circulatory death should remain a consideration; however, an understanding of inherent risks and limitations is necessary.

  4. Considerations of sex and gender differences in preclinical and clinical trials.

    PubMed

    Raz, Limor; Miller, Virginia M

    2012-01-01

    Women continue to be underrepresented in clinical trials, particularly in Phases I and II of experimental drug studies in spite of legislative guidelines in the USA, Canada, the European Union, Australia, and Japan requiring the inclusion of women in clinical trials. As such, women remain a vulnerable population subject to the adverse effects of pharmacological therapies. Thus, women experience higher rates of adverse drug reactions than do men and for women of reproductive age or who may be pregnant, therapeutic options may be limited. This chapter provides a brief history of inclusion of sex and gender as variables in clinical trials, summarizes governmental legislation for consideration of sex and gender in clinical trials and provides specific examples of drugs which have been withdrawn from the market because of side effects in women. Additional information related to sex and gender in preclinical testing, trial design, challenges to recruitment of women for clinical trials and statistical methods for analysis of data also is considered.

  5. Comprehensive Identification of Proteins from MALDI Imaging*

    PubMed Central

    Maier, Stefan K.; Hahne, Hannes; Gholami, Amin Moghaddas; Balluff, Benjamin; Meding, Stephan; Schoene, Cédrik; Walch, Axel K.; Kuster, Bernhard

    2013-01-01

    Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a powerful tool for the visualization of proteins in tissues and has demonstrated considerable diagnostic and prognostic value. One main challenge is that the molecular identity of such potential biomarkers mostly remains unknown. We introduce a generic method that removes this issue by systematically identifying the proteins embedded in the MALDI matrix using a combination of bottom-up and top-down proteomics. The analyses of ten human tissues lead to the identification of 1400 abundant and soluble proteins constituting the set of proteins detectable by MALDI IMS including >90% of all IMS biomarkers reported in the literature. Top-down analysis of the matrix proteome identified 124 mostly N- and C-terminally fragmented proteins indicating considerable protein processing activity in tissues. All protein identification data from this study as well as the IMS literature has been deposited into MaTisse, a new publically available database, which we anticipate will become a valuable resource for the IMS community. PMID:23782541

  6. The central nervous system--an additional consideration in 'rotator cuff tendinopathy' and a potential basis for understanding response to loaded therapeutic exercise.

    PubMed

    Littlewood, Chris; Malliaras, Peter; Bateman, Marcus; Stace, Richmond; May, Stephen; Walters, Stephen

    2013-12-01

    Tendinopathy is a term used to describe a painful tendon disorder but despite being a well-recognised clinical presentation, a definitive understanding of the pathoaetiology of rotator cuff tendinopathy remains elusive. Current explanatory models, which relate to peripherally driven nocioceptive mechanisms secondary to structural abnormality, or failed healing, appear inadequate on their own in the context of current literature. In light of these limitations this paper presents an extension to current models that incorporates the integral role of the central nervous system in the pain experience. The role of the central nervous system (CNS) is described and justified along with a potential rationale to explain the favourable response to loaded therapeutic exercises demonstrated by previous studies. This additional consideration has the potential to offer a useful way to explain pain to patients, for clinicians to prescribe appropriate therapeutic management strategies and for researchers to advance knowledge in relation to this clinically challenging problem. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Theoretical Borderlands: Using Multiple Theoretical Perspectives to Challenge Inequitable Power Structures in Student Development Theory

    ERIC Educational Resources Information Center

    Abes, Elisa S.

    2009-01-01

    This article is an exploration of possibilities and methodological considerations for using multiple theoretical perspectives in research that challenges inequitable power structures in student development theory. Specifically, I explore methodological considerations when partnering queer theory and constructivism in research on lesbian identity…

  8. Ethical research on the implementation of DRGs in Switzerland--a challenging project.

    PubMed

    Wild, Verina; Pfister, Eliane; Biller-Andorno, Nikola

    2012-08-09

    Diagnosis Related Groups (DRGs) are currently being introduced on a national scale as a prospective reimbursement scheme in Swiss in-patient hospital care, replacing any remaining retrospective day-rate arrangements. DRGs are expected to promote transparency and efficiency while helping to contain health care costs. The governmental decision to introduce DRGs has caused considerable controversy among different stakeholders, due to diverging appraisals of what will happen when DRGs are introduced as an economic management tool in Switzerland. The controversial discourse on DRGs is particularly interesting from an ethical point of view, since all arguments inevitably contain ethical considerations. In this paper we summarise the results of our exploratory ethical studies that have led to a larger research project funded by the Swiss National Science Foundation: "Impact of Diagnosis-Related Groups (DRGs) on patient care and professional practice" (IDoC). In section 1: 'Developing an understanding of the ethical issues at stake' we briefly explain how DRGs work, what the intended effects are, what the public is concerned about and what the scientific research tells us so far. In section 2: 'Developing an ethical framework for research on DRGs in Switzerland' we summarise the ethical issues and explain the ethical framework we will use in order to perform research on the complex issue of DRGs in Switzerland. Only once a profound understanding of the challenges exists can research on the ethical implications of DRGs be successful.

  9. Measuring and managing health system performance: An update from New Zealand.

    PubMed

    Chalmers, Linda Maree; Ashton, Toni; Tenbensel, Tim

    2017-08-01

    In July 2016, New Zealand introduced a new approach to measuring and monitoring health system performance. This 'Systems Level Measure Framework' (SLMF) has evolved from the Integrated Performance and Incentive Framework (IPIF) previously reported in this journal. The SLMF is designed to stimulate a 'whole of system' approach that requires inter-organisational collaboration. Local 'Alliances' between government and non-government health sector organisations are responsible for planning and achieving improved health system outcomes such as reducing ambulatory sensitive hospitalisation for young children, and reducing acute hospital bed days. It marks a shift from the previous regime of output and process targets, and from a pay-for-performance approach to primary care. Some elements of the earlier IPIF proposal, such as general practice quality measures, and tiered levels of performance, were not included in the SLM framework. The focus on health system outcomes demonstrates policy commitment to effective integration of health services. However, there remain considerable challenges to successful implementation. An outcomes framework makes it challenging to attribute changes in outcomes to organisational and collaborative strategies. At the local level, the strength and functioning of collaborative relationships between organisations vary considerably. The extent and pace of change may also be constrained by existing funding arrangements in the health system. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Hair loss and regeneration performed on animal models

    PubMed Central

    ORASAN, MEDA SANDRA; ROMAN, IULIA IOANA; CONEAC, ANDREI; MURESAN, ADRIANA; ORASAN, REMUS IOAN

    2016-01-01

    Research in the field of reversal hair loss remains a challenging subject. As Minoxidil 2% or 5% and Finasteride are so far the only FDA approved topical treatments for inducing hair regrowth, research is necessary in order to improve therapeutical approach in alopecia. In vitro studies have focused on cultures of a cell type - dermal papilla or organ culture of isolated cell follicles. In vivo research on this topic was performed on mice, rats, hamsters, rabbits, sheep and monkeys, taking into consideration the advantages and disadvantages of each animal model and the depilation options. Further studies are required not only to compare the efficiency of different therapies but more importantly to establish their long term safety. PMID:27547051

  11. Protons -- The Future of Radiation Therapy?

    NASA Astrophysics Data System (ADS)

    Avery, Steven

    2007-03-01

    Cancer is the 2^nd highest cause of death in the United States. The challenges of controlling this disease remain more difficult as the population lives longer. Proton therapy offers another choice in the management of cancer care. Proton therapy has existed since the late 1950s and the first hospital based center in the United States opened in 1990. Since that time four hospital based proton centers are treating patients with other centers either under construction or under consideration. This talk will focus on an introduction to proton therapy: it's medical advantages over current treatment modalities, accelerators and beam delivery systems, applications to clinical radiation oncology and the future outlook for proton therapy.

  12. Next-generation sequencing: hype and hope for development of personalized radiation therapy?

    PubMed

    Tinhofer, Ingeborg; Niehr, Franziska; Konschak, Robert; Liebs, Sandra; Munz, Matthias; Stenzinger, Albrecht; Weichert, Wilko; Keilholz, Ulrich; Budach, Volker

    2015-08-28

    The introduction of next-generation sequencing (NGS) in the field of cancer research has boosted worldwide efforts of genome-wide personalized oncology aiming at identifying predictive biomarkers and novel actionable targets. Despite considerable progress in understanding the molecular biology of distinct cancer entities by the use of this revolutionary technology and despite contemporaneous innovations in drug development, translation of NGS findings into improved concepts for cancer treatment remains a challenge. The aim of this article is to describe shortly the NGS platforms for DNA sequencing and in more detail key achievements and unresolved hurdles. A special focus will be given on potential clinical applications of this innovative technique in the field of radiation oncology.

  13. Out-patient management of chronic heart failure.

    PubMed

    Terrovitis, John V; Anastasiou-Nana, Maria I; Nanas, John N

    2005-09-01

    Chronic heart failure is a clinical syndrome associated with an ominous long-term prognosis and major economic consequences for Western societies. In recent years, considerable progress has been made in the pharmacological management of heart failure, and several treatments have been confirmed to confer survival and symptomatic benefits. However, pharmaceuticals remain underutilised, and the combination of several different drugs present challenges for their optimal prescription, requiring a thorough knowledge of potential side effects and complex interactions. This article reviews in detail the evidence pertaining to the out-patient pharmacological management of chronic heart failure, and offers recommendations on the use of various drugs in complex clinical conditions, or in areas of ongoing controversy.

  14. 'If they have a girlfriend, they have five girlfriends': Accountability and sexism in volunteer workers' talk about HIV/AIDS in a South African health setting.

    PubMed

    McVittie, Chris; McKinlay, Andy; Ranjbar, Vania

    2018-02-01

    Significant challenges remain in tackling the global HIV/AIDS epidemic. Effective action requires both appropriate policy at a global level and informed practice on the local level. Here, we report how workers in a project in Johannesburg, South Africa, make sense of HIV transmission. Discourse analysis of data from interviews with 63 participants shows that project workers routinely attribute transmission to men's sexual relationships with multiple female partners. This explanation is so pervasive that it renders invisible other routes to transmission. Absence of consideration of other routes to infection potentially restricts front-line practice, so hindering local attempts to tackle HIV/AIDS.

  15. Caring for homeless persons with serious mental illness in general hospitals.

    PubMed

    Bauer, Leah K; Baggett, Travis P; Stern, Theodore A; O'Connell, Jim J; Shtasel, Derri

    2013-01-01

    The care of homeless persons with serious mental illness remains a common and challenging problem in general hospital settings. This article aims to review data on homelessness and its psychiatric comorbidities, and to expand the skills of providers who encounter homeless individuals in general hospital settings. Literature review reveals patient, provider, and systems factors that contribute to suboptimal health outcomes in homeless individuals. Diagnostic rigor, integrated medical and psychiatric care, trauma-informed interventions, special considerations in capacity evaluations, and health care reform initiatives can improve the treatment of homeless persons with serious mental illness. Copyright © 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  16. Supramolecular Approaches to Nanoscale Morphological Control in Organic Solar Cells

    PubMed Central

    Haruk, Alexander M.; Mativetsky, Jeffrey M.

    2015-01-01

    Having recently surpassed 10% efficiency, solar cells based on organic molecules are poised to become a viable low-cost clean energy source with the added advantages of mechanical flexibility and light weight. The best-performing organic solar cells rely on a nanostructured active layer morphology consisting of a complex organization of electron donating and electron accepting molecules. Although much progress has been made in designing new donor and acceptor molecules, rational control over active layer morphology remains a central challenge. Long-term device stability is another important consideration that needs to be addressed. This review highlights supramolecular strategies for generating highly stable nanostructured organic photovoltaic active materials by design. PMID:26110382

  17. An overview of age estimation in forensic anthropology: perspectives and practical considerations.

    PubMed

    Márquez-Grant, Nicholas

    2015-01-01

    Information on methods of age estimation in physical anthropology, in particular with regard to age-at-death from human skeletal remains, is widely available in the literature. However, the practicalities and real challenges faced in forensic casework are not always highlighted. To provide a practitioner's perspective, regarding age estimation in forensic anthropology (both in the living as well as the dead), with an emphasis on the types of cases, the value of such work and its challenges and limitations. The paper reviews the current literature on age estimation with a focus on forensic anthropology, but it also brings the author's personal perspective derived from a number of forensic cases. Although much is known about what methods to use, but not always how to apply them, little attention has been given in the literature to the real practicalities faced by forensic anthropologists, for example: the challenges in different types of scenarios; how to report age estimations; responsibilities; and ethical concerns. This paper gathers some of these aspects into one overview which includes the value of such work and the practical challenges, not necessarily with the methods themselves, but also with regard to how these are applied in the different cases where age estimation is required.

  18. Language Teacher Identities in the Southern United States: Transforming Rural Schools

    ERIC Educational Resources Information Center

    Fogle, Lyn Wright; Moser, Kelly

    2017-01-01

    Foreign language (FL) and English as a Second Language (ESL) teaching present considerable challenges in the rural U.S. South. Local language ideologies, budgetary considerations, and challenges in other curricular areas (e.g., math and science) lead to marginalizing both FL and ESL in schools. This article examines the personal and professional…

  19. Overcoming the glass ceiling: views from the cellar and the roof.

    PubMed

    McCrady, Barbara S

    2012-12-01

    Women's experiences as professionals and behavior therapists have changed considerably in the past 40 years. The author describes early challenges and experiences of discrimination as a young female professional. Although women's opportunities have improved considerably, women still experience unique career challenges and choices. The author provides some suggestions for women's career development.

  20. HTA programme response to the challenges of dealing with orphan medicinal products: Process evaluation in selected European countries.

    PubMed

    Nicod, Elena; Annemans, Lieven; Bucsics, Anna; Lee, Anne; Upadhyaya, Sheela; Facey, Karen

    2017-03-28

    Challenges commonly encountered in HTA of orphan medicinal products (OMPs) were identified in Advance-HTA. Since then, new initiatives have been developed to specifically address issues related to HTA of OMPs. This study aimed to understand why these new HTA initiatives in England, Scotland and at European-level were established and whether they resolve the challenges of OMPs. The work of Advance-HTA was updated with a literature review and a conceptual framework of clinical, regulatory and economic challenges for OMPs was developed. The new HTA programmes were critiqued against the conceptual framework and outstanding challenges identified. The new programmes in England and Scotland recognise the challenges identified in demonstrating the value of ultra-OMPs (and OMPs) and that they require a different process to standard HTA approaches. Wider considerations of disease and treatment experiences from a multi-stakeholder standpoint are needed, combined with other measures to deal with uncertainty (e.g. managed entry agreements). While approaches to assessing this new view of value of OMPs, extending beyond cost/QALY frameworks, differ, their criteria are similar. These are complemented by a European initiative that fosters multi-stakeholder dialogue and consensus about value determinants throughout the life-cycle of an OMP. New HTA programmes specific to OMPs have been developed but questions remain about whether they sufficiently capture value and manage uncertainty in clinical practice. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Applying chemical engineering concepts to non-thermal plasma reactors

    NASA Astrophysics Data System (ADS)

    Pedro AFFONSO, NOBREGA; Alain, GAUNAND; Vandad, ROHANI; François, CAUNEAU; Laurent, FULCHERI

    2018-06-01

    Process scale-up remains a considerable challenge for environmental applications of non-thermal plasmas. Undersanding the impact of reactor hydrodynamics in the performance of the process is a key step to overcome this challenge. In this work, we apply chemical engineering concepts to analyse the impact that different non-thermal plasma reactor configurations and regimes, such as laminar or plug flow, may have on the reactor performance. We do this in the particular context of the removal of pollutants by non-thermal plasmas, for which a simplified model is available. We generalise this model to different reactor configurations and, under certain hypotheses, we show that a reactor in the laminar regime may have a behaviour significantly different from one in the plug flow regime, often assumed in the non-thermal plasma literature. On the other hand, we show that a packed-bed reactor behaves very similarly to one in the plug flow regime. Beyond those results, the reader will find in this work a quick introduction to chemical reaction engineering concepts.

  2. Methodological issues in the design and analyses of neonatal research studies: Experience of the NICHD Neonatal Research Network.

    PubMed

    Das, Abhik; Tyson, Jon; Pedroza, Claudia; Schmidt, Barbara; Gantz, Marie; Wallace, Dennis; Truog, William E; Higgins, Rosemary D

    2016-10-01

    Impressive advances in neonatology have occurred over the 30 years of life of The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN). However, substantial room for improvement remains in investigating and further developing the evidence base for improving outcomes among the extremely premature. We discuss some of the specific methodological challenges in the statistical design and analysis of randomized trials and observational studies in this population. Challenges faced by the NRN include designing trials for unusual or rare outcomes, accounting for and explaining center variations, identifying other subgroup differences, and balancing safety and efficacy concerns between short-term hospital outcomes and longer-term neurodevelopmental outcomes. In conclusion, the constellation of unique patient characteristics in neonates calls for broad understanding and careful consideration of the issues identified in this article for conducting rigorous studies in this population. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Some considerations concerning the challenge of incorporating social variables into epidemiological models of infectious disease transmission.

    PubMed

    Barnett, Tony; Fournié, Guillaume; Gupta, Sunetra; Seeley, Janet

    2015-01-01

    Incorporation of 'social' variables into epidemiological models remains a challenge. Too much detail and models cease to be useful; too little and the very notion of infection - a highly social process in human populations - may be considered with little reference to the social. The French sociologist Émile Durkheim proposed that the scientific study of society required identification and study of 'social currents'. Such 'currents' are what we might today describe as 'emergent properties', specifiable variables appertaining to individuals and groups, which represent the perspectives of social actors as they experience the environment in which they live their lives. Here we review the ways in which one particular emergent property, hope, relevant to a range of epidemiological situations, might be used in epidemiological modelling of infectious diseases in human populations. We also indicate how such an approach might be extended to include a range of other potential emergent properties to represent complex social and economic processes bearing on infectious disease transmission.

  4. Isotope effect of mercury diffusion in air

    PubMed Central

    Koster van Groos, Paul G.; Esser, Bradley K.; Williams, Ross W.; Hunt, James R.

    2014-01-01

    Identifying and reducing impacts from mercury sources in the environment remains a considerable challenge and requires process based models to quantify mercury stocks and flows. The stable isotope composition of mercury in environmental samples can help address this challenge by serving as a tracer of specific sources and processes. Mercury isotope variations are small and result only from isotope fractionation during transport, equilibrium, and transformation processes. Because these processes occur in both industrial and environmental settings, knowledge of their associated isotope effects is required to interpret mercury isotope data. To improve the mechanistic modeling of mercury isotope effects during gas phase diffusion, an experimental program tested the applicability of kinetic gas theory. Gas-phase elemental mercury diffusion through small bore needles from finite sources demonstrated mass dependent diffusivities leading to isotope fractionation described by a Rayleigh distillation model. The measured relative atomic diffusivities among mercury isotopes in air are large and in agreement with kinetic gas theory. Mercury diffusion in air offers a reasonable explanation of recent field results reported in the literature. PMID:24364380

  5. The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities

    PubMed Central

    Hammitt, Laura L.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.

    2017-01-01

    Abstract Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. PMID:28575369

  6. Mucosal melanoma: a clinically and biologically unique disease entity.

    PubMed

    Carvajal, Richard D; Spencer, Sharon A; Lydiatt, William

    2012-03-01

    Mucosal melanoma (MM) is an aggressive and clinically complex malignancy made more challenging by its relative rarity. Because of the rarity of MM as a whole, and because of the unique biology and clinical challenges of MM arising from each anatomic location, understanding of this disease and its optimal management remains limited. The impact of various treatment strategies on disease control and survival has been difficult to assess because of the small size of most reported series of MM arising from any one particular site, the retrospective nature of most series, and the lack of a uniform comprehensive staging system for this disease. This article summarizes the clinical, pathologic, and molecular features, and the diagnostic and therapeutic considerations for the management of MM, underscoring the similarities and differences from cutaneous melanoma. Furthermore, the distinct clinical features and management implications unique to melanoma arising from the mucosal surfaces of the head and neck, the anorectal region, and the female genital tract are highlighted.

  7. Breeding blueberries for a changing global environment: a review

    PubMed Central

    Lobos, Gustavo A.; Hancock, James F.

    2015-01-01

    Today, blueberries are recognized worldwide as one of the foremost health foods, becoming one of the crops with the highest productive and commercial projections. Over the last 100 years, the geographical area where highbush blueberries are grown has extended dramatically into hotter and drier environments. The expansion of highbush blueberry growing into warmer regions will be challenged in the future by increases in average global temperature and extreme fluctuations in temperature and rainfall patterns. Considerable genetic variability exists within the blueberry gene pool that breeders can use to meet these challenges, but traditional selection techniques can be slow and inefficient and the precise adaptations of genotypes often remain hidden. Marker assisted breeding (MAB) and phenomics could aid greatly in identifying those individuals carrying adventitious traits, increasing selection efficiency and shortening the rate of cultivar release. While phenomics have begun to be used in the breeding of grain crops in the last 10 years, their use in fruit breeding programs it is almost non-existent. PMID:26483803

  8. Adaptive management of natural resources-framework and issues

    USGS Publications Warehouse

    Williams, B.K.

    2011-01-01

    Adaptive management, an approach for simultaneously managing and learning about natural resources, has been around for several decades. Interest in adaptive decision making has grown steadily over that time, and by now many in natural resources conservation claim that adaptive management is the approach they use in meeting their resource management responsibilities. Yet there remains considerable ambiguity about what adaptive management actually is, and how it is to be implemented by practitioners. The objective of this paper is to present a framework and conditions for adaptive decision making, and discuss some important challenges in its application. Adaptive management is described as a two-phase process of deliberative and iterative phases, which are implemented sequentially over the timeframe of an application. Key elements, processes, and issues in adaptive decision making are highlighted in terms of this framework. Special emphasis is given to the question of geographic scale, the difficulties presented by non-stationarity, and organizational challenges in implementing adaptive management. ?? 2010.

  9. Isotope effect of mercury diffusion in air.

    PubMed

    Koster van Groos, Paul G; Esser, Bradley K; Williams, Ross W; Hunt, James R

    2014-01-01

    Identifying and reducing impacts from mercury sources in the environment remains a considerable challenge and requires process based models to quantify mercury stocks and flows. The stable isotope composition of mercury in environmental samples can help address this challenge by serving as a tracer of specific sources and processes. Mercury isotope variations are small and result only from isotope fractionation during transport, equilibrium, and transformation processes. Because these processes occur in both industrial and environmental settings, knowledge of their associated isotope effects is required to interpret mercury isotope data. To improve the mechanistic modeling of mercury isotope effects during gas phase diffusion, an experimental program tested the applicability of kinetic gas theory. Gas-phase elemental mercury diffusion through small bore needles from finite sources demonstrated mass dependent diffusivities leading to isotope fractionation described by a Rayleigh distillation model. The measured relative atomic diffusivities among mercury isotopes in air are large and in agreement with kinetic gas theory. Mercury diffusion in air offers a reasonable explanation of recent field results reported in the literature.

  10. Adjuvant chemotherapy decisions in clinical practice for early-stage node-negative, estrogen receptor-positive, HER2-negative breast cancer: challenges and considerations.

    PubMed

    Nagaraj, Gayathri; Ma, Cynthia X

    2013-03-01

    Decisions regarding adjuvant chemotherapy for patients with estrogen receptor (ER)-positive, HER2-negative, lymph node-negative breast cancer have traditionally relied on clinical and pathologic parameters. However, the molecular heterogeneity and the complex tumor genome demand more sophisticated approaches to the problem. Several multigene-based assays have been developed to better prognosticate the risk of recurrence and death and predict benefit of therapy in this patient population. Oncologists are often faced with the challenge of incorporating these various complex genome-based biomarkers along with the traditional biomarkers in clinical decision-making. The NCCN Clinical Practice Guidelines in Oncology for Breast Cancer are helpful in providing a general recommendation. However, uncertainty remains in the absence of definitive data for various clinical scenarios. This case report describes a postmenopausal woman with stage I breast cancer that is low-grade and ER-rich, and has an intermediate Oncotype DX recurrence score of 28.

  11. Nanoparticle Exposure and Hormetic Dose–Responses: An Update

    PubMed Central

    Leso, Veruscka; Fontana, Luca; Calabrese, Edward J.

    2018-01-01

    The concept of hormesis, as an adaptive response of biological systems to moderate environmental challenges, has raised considerable nano-toxicological interests in view of the rapid pace of production and application of even more innovative nanomaterials and the expected increasing likelihood of environmental and human exposure to low-dose concentrations. Therefore, the aim of this review is to provide an update of the current knowledge concerning the biphasic dose–responses induced by nanoparticle exposure. The evidence presented confirmed and extended our previous findings, showing that hormesis is a generalized adaptive response which may be further generalized to nanoscale xenobiotic challenges. Nanoparticle physico-chemical properties emerged as possible features affecting biphasic relationships, although the molecular mechanisms underlining such influences remain to be fully understood, especially in experimental settings resembling long-term and low-dose realistic environmental exposure scenarios. Further investigation is necessary to achieve helpful information for a suitable assessment of nanomaterial risks at the low-dose range for both the ecosystem function and the human health. PMID:29534471

  12. MassTRIX: mass translator into pathways.

    PubMed

    Suhre, Karsten; Schmitt-Kopplin, Philippe

    2008-07-01

    Recent technical advances in mass spectrometry (MS) have brought the field of metabolomics to a point where large numbers of metabolites from numerous prokaryotic and eukaryotic organisms can now be easily and precisely detected. The challenge today lies in the correct annotation of these metabolites on the basis of their accurate measured masses. Assignment of bulk chemical formula is generally possible, but without consideration of the biological and genomic context, concrete metabolite annotations remain difficult and uncertain. MassTRIX responds to this challenge by providing a hypothesis-driven approach to high precision MS data annotation. It presents the identified chemical compounds in their genomic context as differentially colored objects on KEGG pathway maps. Information on gene transcription or differences in the gene complement (e.g. samples from different bacterial strains) can be easily added. The user can thus interpret the metabolic state of the organism in the context of its potential and, in the case of submitted transcriptomics data, real enzymatic capacities. The MassTRIX web server is freely accessible at http://masstrix.org.

  13. Capacity Payments in Restructured Markets under Low and High Penetration Levels of Renewable Energy

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

    Jenkin, Thomas; Beiter, Philipp; Margolis, Robert

    There is considerable debate about the degree to which restructured markets perform successfully in their use of capacity markets. In providing appropriate incentives for new and existing generation to meet reliability requirements, a variety of capacity market designs have developed across RTOs and ISOs in the United States and internationally. Growing levels of variable renewable energy (VRE) resources arguably create new challenges for capacity market designs, because VREs suppress energy prices while providing relatively little capacity, with these effects increase with VRE penetration. The purpose of this report is threefold. First, we provide a brief outline of the purpose andmore » design of various capacity markets under consideration using variable resource requirement (VRR) demand curves. Second, we discuss some of the main challenges raised in existing literature and a set of interviews that we conducted with market participants, regulators, and observers, including where there substantive differences in opinion. Third, we consider some of the challenges that may be specific to higher penetration levels of VRE. While the well known 'merit order' effect from VRE can be expected to suppress wholesale energy prices and revenue, this may be partly mitigated by increased capacity payments and the greater importance of AS payments for flexible capacity. The potential for greater reliance on capacity markets for generator revenues may amplify any inefficiency and costs associated with capacity price volatility and other suboptimal market design choices. Regulatory intervention to ensure adequate capacity payments and ancillary service revenue may become more prevalent under current market designs as the timescale for market signals shifts increasingly from near term (e.g., day-ahead in wholesale electricity markets) to longer term (annual intervals in capacity markets). Our review and discussion with market participants suggest substantive challenges may remain in implementing capacity markets that provide both adequate operational and investment incentives, particularly under high-VRE scenarios with greater need for flexible capacity.« less

  14. The promising future of microalgae: current status, challenges, and optimization of a sustainable and renewable industry for biofuels, feed, and other products.

    PubMed

    Khan, Muhammad Imran; Shin, Jin Hyuk; Kim, Jong Deog

    2018-03-05

    Microalgae have recently attracted considerable interest worldwide, due to their extensive application potential in the renewable energy, biopharmaceutical, and nutraceutical industries. Microalgae are renewable, sustainable, and economical sources of biofuels, bioactive medicinal products, and food ingredients. Several microalgae species have been investigated for their potential as value-added products with remarkable pharmacological and biological qualities. As biofuels, they are a perfect substitute to liquid fossil fuels with respect to cost, renewability, and environmental concerns. Microalgae have a significant ability to convert atmospheric CO 2 to useful products such as carbohydrates, lipids, and other bioactive metabolites. Although microalgae are feasible sources for bioenergy and biopharmaceuticals in general, some limitations and challenges remain, which must be overcome to upgrade the technology from pilot-phase to industrial level. The most challenging and crucial issues are enhancing microalgae growth rate and product synthesis, dewatering algae culture for biomass production, pretreating biomass, and optimizing the fermentation process in case of algal bioethanol production. The present review describes the advantages of microalgae for the production of biofuels and various bioactive compounds and discusses culturing parameters.

  15. Policy Support and Resources Mobilization for the National Schistosomiasis Control Programme in The People's Republic of China.

    PubMed

    Zhu, H; Yap, P; Utzinger, J; Jia, T-W; Li, S-Z; Huang, X-B; Cai, S-X

    2016-01-01

    Schistosomiasis remains a public health problem in many developing countries around the world. After the founding of The People's Republic of China, from 1949 till date, all levels of government, from central to local, have been attaching great importance to schistosomiasis control in The People's Republic of China. With considerable policy support and resources mobilization, the national schistosomiasis control programmes have been implemented during the past 65years. Here, we summarize the successful experience of schistosomiasis control during the process. Recommendations for the future management of the Chinese national schistosomiasis elimination programme are put forward after considering the remaining challenges, shortcomings and lessons learnt from 65years of schistosomiasis control drives in The People's Republic of China. They will help to sustain past achievements, foster the attainment of the ultimate goal of schistosomiasis elimination for the country and provide reference for schistosomiasis control programme in other countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Intra-abdominal pedicled rectus abdominis muscle flap for treatment of high-output enterocutaneous fistulae: case reports and review of literature.

    PubMed

    Carey, Joseph N; Sheckter, Clifford C; Watt, Andrew J; Lee, Gordon K

    2013-08-01

    Despite advances in nutritional supplementation, sepsis management, percutaneous drainage and surgical technique, enterocutaneous fistulae remain a considerable source of morbidity and mortality. Use of adjunctive modalities including negative pressure wound therapy and fibrin glue have been shown to improve the rapidity of fistula closure; however, the overall rate of closure remains poor. The challenge of managing chronic, high-output proximal enterocutaneous fistulae can be successfully achieved with appropriate medical management and intra-abdominal placement of pedicled rectus abdominis muscle flaps. We report two cases of recalcitrant high output enterocutaneous fistulae that were treated successfully with pedicled intra-abdominal rectus muscle flaps. Indications for pedicled intra-abdominal rectus muscle flaps include persistent patency despite a reasonable trial of non-operative intervention, failure of traditional operative interventions (serosal patch, Graham patch), and persistent electrolyte and nutritional abnormalities in the setting of a high-output fistula. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  17. Functional trait differences influence neighbourhood interactions in a hyperdiverse Amazonian forest.

    PubMed

    Fortunel, Claire; Valencia, Renato; Wright, S Joseph; Garwood, Nancy C; Kraft, Nathan J B

    2016-09-01

    As distinct community assembly processes can produce similar community patterns, assessing the ecological mechanisms promoting coexistence in hyperdiverse rainforests remains a considerable challenge. We use spatially explicit neighbourhood models of tree growth to quantify how functional trait and phylogenetic similarities predict variation in growth and crowding effects for the 315 most abundant tree species in a 25-ha lowland rainforest plot in Ecuador. We find that functional trait differences reflect variation in (1) species maximum potential growth, (2) the intensity of interspecific interactions for some species, and (3) species sensitivity to neighbours. We find that neighbours influenced tree growth in 28% of the 315 focal tree species. Neighbourhood effects are not detected in the remaining 72%, which may reflect the low statistical power to model rare taxa and/or species insensitivity to neighbours. Our results highlight the spectrum of ways in which functional trait differences can shape community dynamics in highly diverse rainforests. © 2016 John Wiley & Sons Ltd/CNRS.

  18. Online interviewing with interpreters in humanitarian contexts

    PubMed Central

    Chiumento, Anna; Rahman, Atif; Frith, Lucy

    2018-01-01

    ABSTRACT Purpose: Recognising that one way to address the logistical and safety considerations of research conducted in humanitarian emergencies is to use internet communication technologies to facilitate interviews online, this article explores some practical and methodological considerations inherent to qualitative online interviewing. Method: Reflections from a case study of a multi-site research project conducted in post-conflict countries are presented.  Synchronous online cross-language qualitative interviews were conducted in one country.  Although only a small proportion of interviews were conducted online (six out of 35), it remains important to critically consider the impact upon data produced in this way. Results: A range of practical and methodological considerations are discussed, illustrated with examples.  Results suggest that whilst online interviewing has methodological and ethical potential and versatility, there are inherent practical challenges in settings with poor internet and electricity infrastructure.  Notable methodological limitations include barriers to building rapport due to partial visual and non-visual cues, and difficulties interpreting pauses or silences. Conclusions: Drawing upon experiences in this case study, strategies for managing the practical and methodological limitations of online interviewing are suggested, alongside recommendations for supporting future research practice.  These are intended to act as a springboard for further reflection, and operate alongside other conceptual frameworks for online interviewing. PMID:29532739

  19. Online interviewing with interpreters in humanitarian contexts.

    PubMed

    Chiumento, Anna; Machin, Laura; Rahman, Atif; Frith, Lucy

    2018-12-01

    Recognising that one way to address the logistical and safety considerations of research conducted in humanitarian emergencies is to use internet communication technologies to facilitate interviews online, this article explores some practical and methodological considerations inherent to qualitative online interviewing. Reflections from a case study of a multi-site research project conducted in post-conflict countries are presented.  Synchronous online cross-language qualitative interviews were conducted in one country.  Although only a small proportion of interviews were conducted online (six out of 35), it remains important to critically consider the impact upon data produced in this way. A range of practical and methodological considerations are discussed, illustrated with examples.  Results suggest that whilst online interviewing has methodological and ethical potential and versatility, there are inherent practical challenges in settings with poor internet and electricity infrastructure.  Notable methodological limitations include barriers to building rapport due to partial visual and non-visual cues, and difficulties interpreting pauses or silences. Drawing upon experiences in this case study, strategies for managing the practical and methodological limitations of online interviewing are suggested, alongside recommendations for supporting future research practice.  These are intended to act as a springboard for further reflection, and operate alongside other conceptual frameworks for online interviewing.

  20. Predicting protein contact map using evolutionary and physical constraints by integer programming.

    PubMed

    Wang, Zhiyong; Xu, Jinbo

    2013-07-01

    Protein contact map describes the pairwise spatial and functional relationship of residues in a protein and contains key information for protein 3D structure prediction. Although studied extensively, it remains challenging to predict contact map using only sequence information. Most existing methods predict the contact map matrix element-by-element, ignoring correlation among contacts and physical feasibility of the whole-contact map. A couple of recent methods predict contact map by using mutual information, taking into consideration contact correlation and enforcing a sparsity restraint, but these methods demand for a very large number of sequence homologs for the protein under consideration and the resultant contact map may be still physically infeasible. This article presents a novel method PhyCMAP for contact map prediction, integrating both evolutionary and physical restraints by machine learning and integer linear programming. The evolutionary restraints are much more informative than mutual information, and the physical restraints specify more concrete relationship among contacts than the sparsity restraint. As such, our method greatly reduces the solution space of the contact map matrix and, thus, significantly improves prediction accuracy. Experimental results confirm that PhyCMAP outperforms currently popular methods no matter how many sequence homologs are available for the protein under consideration. http://raptorx.uchicago.edu.

  1. A qualitative study of health information technology in the Canadian public health system.

    PubMed

    Zinszer, Kate; Tamblyn, Robyn; Bates, David W; Buckeridge, David L

    2013-05-25

    Although the adoption of health information technology (HIT) has advanced in Canada over the past decade, considerable challenges remain in supporting the development, broad adoption, and effective use of HIT in the public health system. Policy makers and practitioners have long recognized that improvements in HIT infrastructure are necessary to support effective and efficient public health practice. The objective of this study was to identify aspects of health information technology (HIT) policy related to public health in Canada that have succeeded, to identify remaining challenges, and to suggest future directions to improve the adoption and use of HIT in the public health system. A qualitative case study was performed with 24 key stakeholders representing national and provincial organizations responsible for establishing policy and strategic direction for health information technology. Identified benefits of HIT in public health included improved communication among jurisdictions, increased awareness of the need for interoperable systems, and improvement in data standardization. Identified barriers included a lack of national vision and leadership, insufficient investment, and poor conceptualization of the priority areas for implementing HIT in public health. The application of HIT in public health should focus on automating core processes and identifying innovative applications of HIT to advance public health outcomes. The Public Health Agency of Canada should develop the expertise to lead public health HIT policy and should establish a mechanism for coordinating public health stakeholder input on HIT policy.

  2. Quality and clinical supply considerations of Paediatric Investigation Plans for IV preparations-A case study with the FP7 CloSed project.

    PubMed

    Hanning, Sara M; Orlu Gul, Mine; Winslade, Jackie; Baarslag, Manuel A; Neubert, Antje; Tuleu, Catherine

    2016-09-25

    A Paediatric Investigation Plan (PIP) is a development plan that aims to ensure that sufficient data are obtained through studies in paediatrics to support the generation of marketing authorisation of medicines for children. This paper highlights some practical considerations and challenges with respect to PIP submissions and paediatric clinical trials during the pharmaceutical development phase, using the FP7-funded Clonidine for Sedation of Paediatric Patients in the Intensive Care Unit (CloSed) project as a case study. Examples discussed include challenges and considerations regarding formulation development, blinding and randomisation, product labelling and shipment and clinical trial requirements versus requirements for marketing authorisation. A significant quantity of information is required for PIP submissions and it is hoped that future applicants may benefit from an insight into some critical considerations and challenges faced in the CloSed project. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Sustained delivery of biomolecules from gelatin carriers for applications in bone regeneration.

    PubMed

    Song, Jiankang; Leeuwenburgh, Sander Cg

    2014-08-01

    Local delivery of therapeutic biomolecules to stimulate bone regeneration has matured considerably during the past decades, but control over the release of these biomolecules still remains a major challenge. To this end, suitable carriers that allow for tunable spatial and temporal delivery of biomolecules need to be developed. Gelatin is one of the most widely used natural polymers for the controlled and sustained delivery of biomolecules because of its biodegradability, biocompatibility, biosafety and cost-effectiveness. The current study reviews the applications of gelatin as carriers in form of bulk hydrogels, microspheres, nanospheres, colloidal gels and composites for the programmed delivery of commonly used biomolecules for applications in bone regeneration with a specific focus on the relationship between carrier properties and delivery characteristics.

  4. Patient Selection and Procedural Considerations for Coronary Orbital Atherectomy System

    PubMed Central

    Sotomi, Yohei; Shlofmitz, Richard A; Colombo, Antonio; Serruys, Patrick W

    2016-01-01

    Despite advances in technology, percutaneous coronary intervention (PCI) of severely calcified coronary lesions remains challenging. Rotational atherectomy is one of the current therapeutic options to manage calcified lesions, but has a limited role in facilitating the dilation or stenting of lesions that cannot be crossed or expanded with other PCI techniques due to unfavourable clinical outcome in long-term follow-up. However the results of orbital atherectomy presented in the ORBIT I and ORBIT II trials were encouraging. In addition to these encouraging data, necessity for sufficient lesion preparation before implantation of bioresorbable scaffolds lead to resurgence in the use of atherectomy. This article summarises currently available publications on orbital atherectomy (Cardiovascular Systems Inc.) and compares them with rotational atherectomy. PMID:29588702

  5. Massive Open Online Courses in Public Health

    PubMed Central

    Gooding, Ira; Klaas, Brian; Yager, James D.; Kanchanaraksa, Sukon

    2013-01-01

    Massive open online courses (MOOCs) represent a new and potentially transformative model for providing educational opportunities to learners not enrolled in a formal educational program. The authors describe the experience of developing and offering eight MOOCs on a variety of public health topics. Existing institutional infrastructure and experience with both for-credit online education and open educational resources mitigated the institutional risk and resource requirements. Although learners are able to enroll easily and freely and do so in large numbers, there is considerable variety in the level of participation and engagement among enrollees. As a result, comprehensive and accurate assessment of meaningful learning progress remains a major challenge for evaluating the effectiveness of MOOCs for providing public health education. PMID:24350228

  6. Summary of the Tandem Cylinder Solutions from the Benchmark Problems for Airframe Noise Computations-I Workshop

    NASA Technical Reports Server (NTRS)

    Lockard, David P.

    2011-01-01

    Fifteen submissions in the tandem cylinders category of the First Workshop on Benchmark problems for Airframe Noise Computations are summarized. Although the geometry is relatively simple, the problem involves complex physics. Researchers employed various block-structured, overset, unstructured and embedded Cartesian grid techniques and considerable computational resources to simulate the flow. The solutions are compared against each other and experimental data from 2 facilities. Overall, the simulations captured the gross features of the flow, but resolving all the details which would be necessary to compute the noise remains challenging. In particular, how to best simulate the effects of the experimental transition strip, and the associated high Reynolds number effects, was unclear. Furthermore, capturing the spanwise variation proved difficult.

  7. No One Likes a Snitch.

    PubMed

    Redman, Barbara; Caplan, Arthur

    2015-08-01

    Whistleblowers remain essential as complainants in allegations of research misconduct. Frequently internal to the research team, they are poorly protected from acts of retribution, which may deter the reporting of misconduct. In order to perform their important role, whistleblowers must be treated fairly. Draft regulations for whistleblower protection were published for public comment almost a decade ago but never issued (Dahlberg 2013). In the face of the growing challenge of research fraud, we suggest vigorous steps, to include: organizational responsibility to certify the accuracy of research including audit, required whistleblower action in the face of imminent or grave harm to subjects, strengthened legal protections against retaliation including prompt enactment of Federal whistleblower protections and consideration of criminalizing the most egregious cases of research misconduct.

  8. Percutaneous Biopsy of Retrobulbar Masses: Anatomical Considerations and MRI Guidance

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

    Edalat, Faramarz, E-mail: faramarz.edalat@gmail.com; Cazzato, Roberto Luigi; Garnon, Julien

    2017-04-15

    PurposeObtaining adequate tissue from retrobulbar masses remains a challenge. To this end, a new method of retrobulbar mass biopsy using MRI guidance is presented.Materials and MethodsTwo patients (7- and 71-year-old male) with indeterminate retrobulbar masses underwent bioptic and cytological samplings using MR-compatible 18G and 20–22G needles, and multi-planar MR fluoroscopy. An inferior approach was taken to avoid injury to the optic nerve and ophthalmic arteries.ResultsThe two biopsies were completed without complication. The core biopsy resulted in a final diagnosis, whereas the cytological sampling was non-diagnostic.ConclusionPercutaneous MR-guided retrobulbar mass biopsy proved to be feasible and safe in the two cases describedmore » in this report.« less

  9. Aging in Place vs. Relocation for Older Adults with a Neurocognitive Disorder: Applications of Wiseman’s Behavioral Model

    PubMed Central

    Kaplan, Daniel; Andersen, Troy; Lehning, Amanda; Perry, Tam Elisabeth

    2015-01-01

    Some older adults are more vulnerable to housing concerns due to physical and cognitive challenges, including those with a neurocognitive disorder who need extensive support. Environmental gerontology frameworks, including Wiseman’s (1980) Behavioral Model of Elderly Migration, have informed scholarship on aging in place and relocation. It remains unclear, however, the extent to which this conceptual work informs services and supports for older adults, and the Wiseman model has not been applied to people with a neurocognitive disorder. Understanding Wiseman’s model, including considerations for working with families confronting a neurocognitive disorder, can help practitioners ensure that older clients live in settings that best meet their wants and needs. PMID:26016530

  10. Multifaceted Roles of Connexin 43 in Stem Cell Niches.

    PubMed

    Genet, Nafiisha; Bhatt, Neha; Bourdieu, Antonin; Hirschi, Karen K

    2018-01-01

    Considerable progress has been made in the field of stem cell research; nonetheless, the use of stem cells for regenerative medicine therapies, for either endogenous tissue repair or cellular grafts post injury, remains a challenge. To better understand how to maintain stem cell potential in vivo and promote differentiation ex vivo, it is fundamentally important to elucidate the interactions between stem cells and their surrounding partners within their distinct niches. Among the vast array of proteins depicted as mediators for cell-to-cell interactions, connexin-comprised gap junctions play pivotal roles in the regulation of stem cell fate both in vivo and in vitro. This review summarizes and illustrates the current knowledge regarding the multifaceted roles of Cx43, specifically, in various stem cell niches.

  11. Enantioselective Synthesis of All-Carbon Quaternary Centers Structurally Related to Amaryllidaceae Alkaloids.

    PubMed

    Mikušek, Jiří; Jansa, Petr; Jagtap, Pratap R; Vašíček, Tomáš; Císařová, Ivana; Matoušová, Eliška

    2018-05-18

    Enantioselective synthesis of all-carbon quaternary centers remains a considerable challenge for synthetic organic chemists. Here, we report a two-step protocol to synthesize such centers including tandem cyclization/Suzuki cross-coupling followed by halocarbocyclization. During this process, two rings, three new C-C bonds and a stereochemically defined all-carbon quaternary center are formed. The absolute configuration of this center is controlled by the stereochemistry of the adjacent stereocenter, which derives from an appropriate enantioenriched starting material. Using this method, we synthesized polycyclic compounds structurally similar to Amaryllidaceae alkaloids in high enantiomeric excesses. Because these products resemble naturally occurring compounds, our protocol can be used to synthesize various potentially bioactive compounds. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Passive and active adaptive management: Approaches and an example

    USGS Publications Warehouse

    Williams, B.K.

    2011-01-01

    Adaptive management is a framework for resource conservation that promotes iterative learning-based decision making. Yet there remains considerable confusion about what adaptive management entails, and how to actually make resource decisions adaptively. A key but somewhat ambiguous distinction in adaptive management is between active and passive forms of adaptive decision making. The objective of this paper is to illustrate some approaches to active and passive adaptive management with a simple example involving the drawdown of water impoundments on a wildlife refuge. The approaches are illustrated for the drawdown example, and contrasted in terms of objectives, costs, and potential learning rates. Some key challenges to the actual practice of AM are discussed, and tradeoffs between implementation costs and long-term benefits are highlighted. ?? 2010 Elsevier Ltd.

  13. The epidemiology of sexually transmitted infections in the UK: impact of behavior, services and interventions.

    PubMed

    Hughes, Gwenda; Field, Nigel

    2015-01-01

    Sexually transmitted infections (STIs) are a major public health concern. The UK has some of the most advanced STI surveillance systems globally. This article uses national surveillance data to describe remarkable changes in STI epidemiology in the UK over the last century and explores the behavioral and demographic shifts that may explain these trends. The past 10 years have seen considerable improvements in STI service provision and the introduction of national public health interventions. However, sexual health inequalities persist and men who have sex with men, young adults and black ethnic minorities remain a priority for interventions. Technological advances in testing and a shift in sexual health service commissioning arrangements will present both opportunities and challenges in future.

  14. Searching for the elusive gift: advances in talent identification in sport.

    PubMed

    Mann, David L; Dehghansai, Nima; Baker, Joseph

    2017-08-01

    The incentives for sport organizations to identify talented athletes from a young age continue to grow, yet effective talent identification remains a challenging task. This opinion paper examines recent advances in talent identification, focusing in particular on the emergence of new approaches that may offer promise to identify talent (e.g., small-sided games, genetic testing, and advanced statistical analyses). We appraise new multi-disciplinary and large-scale population studies of talent identification, provide a consideration of the most recent psychological predictors of performance, examine the emergence of new approaches that strive to diminish biases in talent identification, and look at the rise in interest in talent identification in Paralympic sport. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  15. How I treat acquired aplastic anemia

    PubMed Central

    Young, Neal S.

    2012-01-01

    Survival in severe aplastic anemia (SAA) has markedly improved in the past 4 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive biologics and drugs, and supportive care. However, management of SAA patients remains challenging, both acutely in addressing the immediate consequences of pancytopenia and in the long term because of the disease's natural history and the consequences of therapy. Recent insights into pathophysiology have practical implications. We review key aspects of differential diagnosis, considerations in the choice of first- and second-line therapies, and the management of patients after immunosuppression, based on both a critical review of the recent literature and our large personal and research protocol experience of bone marrow failure in the Hematology Branch of the National Heart, Lung, and Blood Institute. PMID:22517900

  16. Linking the concept of scale to studies of biological diversity: evolving approaches and tools.

    USGS Publications Warehouse

    Beever, E.A.; Swihart, R.K.; Bestelmeyer, B. T.

    2006-01-01

    Although the concepts of scale and biological diversity independently have received rapidly increasing attention in the scientific literature since the 1980s, the rate at which the two concepts have been investigated jointly has grown much more slowly. We find that scale considerations have been incorporated explicitly into six broad areas of investigation related to biological diversity: (1) heterogeneity within and among ecosystems, (2) disturbance ecology, (3) conservation and restoration, (4) invasion biology, (5) importance of temporal scale for understanding processes, and (6) species responses to environmental heterogeneity. In addition to placing the papers of this Special Feature within the context of brief summaries of the expanding literature on these six topics, we provide an overview of tools useful for integrating scale considerations into studies of biological diversity. Such tools include hierarchical and structural-equation modelling, kriging, variable-width buffers, k-fold cross-validation, and cascading graph diagrams, among others. Finally, we address some of the major challenges and research frontiers that remain, and conclude with a look to the future.

  17. Management of Myelofibrosis-Related Cytopenias.

    PubMed

    Bose, Prithviraj; Verstovsek, Srdan

    2018-05-23

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

  18. Developing a lifelong learning system in Ethiopia: Contextual considerations and propositions

    NASA Astrophysics Data System (ADS)

    Abiy, Dessalegn Samuel; Kabeta, Genet Gelana; Mihiretie, Dawit Mekonnen

    2014-10-01

    Initiated by a "Pilot workshop on developing capacity for establishing lifelong learning systems in UNESCO Member States" held at the UNESCO Institute for Lifelong Learning, the purpose of this study was to develop a Lifelong Learning system in Ethiopia. Preparations for its conceptualisation included the review of relevant national policy documents and an analysis of the Ethiopian educational, economic and social context. Focused group and one-to-one interviews were conducted with policy researchers, experts from the Ministry of Education, adult educators and coordinators at different levels. It emerged that some of the existing policy provisions and contexts reflecting the highly formalised and structured educational opportunities available to Ethiopian youth and adults require re-conceptualisation. Despite the enormous progress made in increasing children's access to primary school, more than two million children remain out of school and adult literacy rates are still far from reaching the targets set both by the United Nations Millennium Development Goals (MDGs) and by national educational programmes. Moreover, as many youth drop out after completing primary education, and as the quality of learning appears to have suffered due to efforts of expansion, it is necessary to revisit the responsiveness of Ethiopia's formal educational provisions in the face of these challenges. Based on the opportunities and challenges identified, the authors explore some major considerations believed to be fundamental in creating a platform for the conceptualisation of Lifelong Learning in the Ethiopian context and conclude with some suggestions for the way forward.

  19. Ethical considerations in forensic genetics research on tissue samples collected post-mortem in Cape Town, South Africa.

    PubMed

    Heathfield, Laura J; Maistry, Sairita; Martin, Lorna J; Ramesar, Raj; de Vries, Jantina

    2017-11-29

    The use of tissue collected at a forensic post-mortem for forensic genetics research purposes remains of ethical concern as the process involves obtaining informed consent from grieving family members. Two forensic genetics research studies using tissue collected from a forensic post-mortem were recently initiated at our institution and were the first of their kind to be conducted in Cape Town, South Africa. This article discusses some of the ethical challenges that were encountered in these research projects. Among these challenges was the adaptation of research workflows to fit in with an exceptionally busy service delivery that is operating with limited resources. Whilst seeking guidance from the literature regarding research on deceased populations, it was noted that next of kin of decedents are not formally recognised as a vulnerable group in the existing ethical and legal frameworks in South Africa. The authors recommend that research in the forensic mortuary setting is approached using guidance for vulnerable groups, and the benefit to risk standard needs to be strongly justified. Lastly, when planning forensic genetics research, consideration must be given to the potential of uncovering incidental findings, funding to validate these findings and the feedback of results to family members; the latter of which is recommended to occur through a genetic counsellor. It is hoped that these experiences will contribute towards a formal framework for conducting forensic genetic research in medico-legal mortuaries in South Africa.

  20. Lessons learnt from 12 oral cholera vaccine campaigns in resource-poor settings.

    PubMed

    Hsiao, Amber; Desai, Sachin N; Mogasale, Vittal; Excler, Jean-Louis; Digilio, Laura

    2017-04-01

    Improving water and sanitation is the preferred choice for cholera control in the long-term. Nevertheless, vaccination is an available tool that has been shown to be a cost-effective option for cholera prevention in endemic countries or during outbreaks. In 2011 the first low-cost oral cholera vaccine for international use was given prequalification by the World Health Organization (WHO). To increase and prioritize use of the vaccine, WHO created a global stockpile in 2013 from which countries may request oral cholera vaccine for reactive campaigns. WHO has issued specific guidelines for applying for the vaccine, which was previously in short supply (despite prequalification for a second oral vaccine in 2015). The addition of a third WHO-prequalified oral cholera vaccine in 2016 is expected to increase the global stockpile considerably and alleviate supply issues. However, prioritization and best use of the vaccine (e.g. how, when and where to use) will remain challenges. We describe 12 past oral cholera vaccine campaigns, conducted in settings with varying burdens of cholera. These case studies illustrate three key challenges faced in the use of the oral cholera vaccines: regulatory hurdles, cold chain logistics and vaccine coverage and uptake. To pave the way for the introduction of current and future oral cholera vaccines, we discuss operational challenges and make recommendations for future research with respect to each of these challenges.

  1. Pathogen profile of clinical mastitis in Irish milk-recording herds reveals a complex aetiology.

    PubMed

    Keane, O M; Budd, K E; Flynn, J; McCoy, F

    2013-07-06

    Effective mastitis control requires knowledge of the predominant pathogen challenges on the farm. In order to quantify this challenge, the aetiological agents associated with clinical mastitis in 30 milk-recording dairy herds in Ireland over a complete lactation were investigated. Standard bacteriology was performed on 630 pretreatment quarter milk samples, of which 56 per cent were culture-positive, 42 per cent culture-negative and 2 per cent contaminated. Two micro-organisms were isolated from almost 5 per cent of the culture-positive samples. The bacteria isolated were Staphylococcus aureus (23 per cent), Streptococcus uberis (17 per cent), Escherichia coli (9 per cent), Streptococcus species (6 per cent), coagulase-negative Staphylococci (4 per cent) and other species (1 per cent). A wide variety of bacterial species were associated with clinical mastitis, with S aureus the most prevalent pathogen overall, followed by S uberis. However, the bacterial challenges varied widely from farm to farm. In comparison with previous reports, in the present study, the contagious pathogens S aureus and Streptococcus agalactiae were less commonly associated with clinical mastitis, whereas, the environmental pathogens S uberis and E coli were found more commonly associated with clinical mastitis. While S aureus remains the pathogen most commonly associated with intramammary infection in these herds, environmental pathogens, such as S uberis and E coli also present a considerable challenge.

  2. Lessons learnt from 12 oral cholera vaccine campaigns in resource-poor settings

    PubMed Central

    Desai, Sachin N; Mogasale, Vittal; Excler, Jean-Louis; Digilio, Laura

    2017-01-01

    Abstract Improving water and sanitation is the preferred choice for cholera control in the long-term. Nevertheless, vaccination is an available tool that has been shown to be a cost-effective option for cholera prevention in endemic countries or during outbreaks. In 2011 the first low-cost oral cholera vaccine for international use was given prequalification by the World Health Organization (WHO). To increase and prioritize use of the vaccine, WHO created a global stockpile in 2013 from which countries may request oral cholera vaccine for reactive campaigns. WHO has issued specific guidelines for applying for the vaccine, which was previously in short supply (despite prequalification for a second oral vaccine in 2015). The addition of a third WHO-prequalified oral cholera vaccine in 2016 is expected to increase the global stockpile considerably and alleviate supply issues. However, prioritization and best use of the vaccine (e.g. how, when and where to use) will remain challenges. We describe 12 past oral cholera vaccine campaigns, conducted in settings with varying burdens of cholera. These case studies illustrate three key challenges faced in the use of the oral cholera vaccines: regulatory hurdles, cold chain logistics and vaccine coverage and uptake. To pave the way for the introduction of current and future oral cholera vaccines, we discuss operational challenges and make recommendations for future research with respect to each of these challenges. PMID:28479625

  3. Satellite Tasking via a Tablet Computer

    DTIC Science & Technology

    2015-09-01

    connectivity have helped to overcome the challenges of information delivery , but there remains the challenge of real-time information. This thesis...have helped to overcome the challenges of information delivery , but there remains the challenge of real-time information. This thesis examines the...76  3.  Integration with Existing Programs for Access and Dissemination of Imagery

  4. Ready-to-use foods for management of moderate acute malnutrition: considerations for scaling up production and use in programs.

    PubMed

    Osendarp, Saskia; Rogers, Beatrice; Ryan, Kelsey; Manary, Mark; Akomo, Peter; Bahwere, Paluku; Belete, Hilina; Zeilani, Mamane; Islam, Munirul; Dibari, Filippo; De Pee, Saskia

    2015-03-01

    Ready-to-use foods are one of the available strategies for the treatment of moderate acute malnutrition (MAM), but challenges remain in the use of these products in programs at scale. This paper focuses on two challenges: the need for cheaper formulations using locally available ingredients that are processed in a safe, reliable, and financially sustainable local production facility; and the effective use of these products in large-scale community-based programs. Linear programming tools can be used successfully to design local compositions that are in line with international guidelines, low in cost, and acceptable, and the efficacy of these local formulations in the treatment of MAM was recently demonstrated in Malawi. The production of local formulations for programs at scale relies on the existence of a reliable and efficient local production facility. Technical assistance may be required in the development of sustainable business models at an early stage in the process, taking into account the stringent product quality and safety criteria and the required investments. The use of ready-to-use products, as of any food supplement, in programs at scale will be affected by the practice of household sharing and diversion of these products for other uses. Additional measures can be considered to account for sharing. These products designed for the treatment and prevention of MAM are to be used in community-based programs and should therefore be used in conjunction with other interventions and designed so that they do not replace the intake of other foods and breastmilk. Remaining challenges and implications for the (operations) research agenda are discussed.

  5. Torsional tapping atomic force microscopy for molecular resolution imaging of soft matter

    NASA Astrophysics Data System (ADS)

    Hobbs, Jamie; Mullin, Nic

    2012-02-01

    Despite considerable advances in image resolution on challenging, soft systems, a method for obtaining molecular resolution on `real' samples with significant surface roughness has remained elusive. Here we will show that a relatively new technique, torsional tapping AFM (TTAFM), is capable of imaging with resolution down to 3.7 Angrstrom on the surface of `bulk' polymer films [1]. In TTAFM T-shaped cantilevers are driven into torsional oscillation. As the tip is offset from the rotation axis this provides a tapping motion. Due to the high frequency and Q of the oscillation and relatively small increase in spring constant, improved cantilever dynamics and force sensitivity are obtained. As the tip offset from the torsional axis is relatively small (typically 25 microns), the optical lever sensitivity is considerably improved compared to flexural oscillation. Combined these give a reduction in noise floor by a factor of 12 just by changing the cantilever geometry. The ensuing low noise allows the use of ultra-sharp `whisker' tips with minimal blunting. As the cantilevers remain soft in the flexural axis, the force when imaging with error is also reduced, further protecting the tip. We will show that this combination allows routine imaging of the molecular structure of semicrystalline polymer films, including chain folds, loose loops and tie-chains in polyethylene, and the helical conformation of polypropylene within the crystal, using a standard, commercial AFM. [4pt] [1] N Mullin, JK Hobbs, PRL 107, 197801 (2011)

  6. Collaboration in natural resource governance: reconciling stakeholder expectations in deer management in Scotland.

    PubMed

    Davies, Althea L; White, Rehema M

    2012-12-15

    The challenges of integrated, adaptive and ecosystem management are leading government agencies to adopt participatory modes of engagement. Collaborative governance is a form of participation in which stakeholders co-produce goals and strategies and share responsibilities and resources. We assess the potential and challenges of collaborative governance as a mechanism to provide an integrated, ecosystem approach to natural resource management, using red deer in Scotland as a case study. Collaborative Deer Management Groups offer a well-established example of a 'bridging organisation', intended to reduce costs and facilitate decision making and learning across institutions and scales. We examine who initiates collaborative processes and why, what roles different actors adopt and how these factors influence the outcomes, particularly at a time of changing values, management and legislative priorities. Our findings demonstrate the need for careful consideration of where and how shared responsibility might be best implemented and sustained as state agencies often remain key to the process, despite the partnership intention. Differing interpretations between agencies and landowners of the degree of autonomy and division of responsibilities involved in 'collaboration' can create tension, while the diversity of landowner priorities brings additional challenges for defining shared goals in red deer management and in other cases. Effective maintenance depends on appropriate role allocation and adoption of responsibilities, definition of convergent values and goals, and establishing communication and trust in institutional networks. Options that may help private stakeholders offset the costs of accepting responsibility for delivering public benefits need to be explicitly addressed to build capacity and support adaptation. This study indicates that collaborative governance has the potential to help reconcile statutory obligations with stakeholder empowerment. The potential of collaboration to reduce the costs of sustainable management remains contentious and, in times of increasing resource constraints, the potential mismatch between resource investment and anticipated goals is likely to become a critical issue, which may challenge the goals and capacity of the state and existing managers. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Advanced imaging of the macrostructure and microstructure of bone

    NASA Technical Reports Server (NTRS)

    Genant, H. K.; Gordon, C.; Jiang, Y.; Link, T. M.; Hans, D.; Majumdar, S.; Lang, T. F.

    2000-01-01

    Noninvasive and/or nondestructive techniques are capable of providing more macro- or microstructural information about bone than standard bone densitometry. Although the latter provides important information about osteoporotic fracture risk, numerous studies indicate that bone strength is only partially explained by bone mineral density. Quantitative assessment of macro- and microstructural features may improve our ability to estimate bone strength. The methods available for quantitatively assessing macrostructure include (besides conventional radiographs) quantitative computed tomography (QCT) and volumetric quantitative computed tomography (vQCT). Methods for assessing microstructure of trabecular bone noninvasively and/or nondestructively include high-resolution computed tomography (hrCT), micro-computed tomography (muCT), high-resolution magnetic resonance (hrMR), and micromagnetic resonance (muMR). vQCT, hrCT and hrMR are generally applicable in vivo; muCT and muMR are principally applicable in vitro. Although considerable progress has been made in the noninvasive and/or nondestructive imaging of the macro- and microstructure of bone, considerable challenges and dilemmas remain. From a technical perspective, the balance between spatial resolution versus sampling size, or between signal-to-noise versus radiation dose or acquisition time, needs further consideration, as do the trade-offs between the complexity and expense of equipment and the availability and accessibility of the methods. The relative merits of in vitro imaging and its ultrahigh resolution but invasiveness versus those of in vivo imaging and its modest resolution but noninvasiveness also deserve careful attention. From a clinical perspective, the challenges for bone imaging include balancing the relative advantages of simple bone densitometry against the more complex architectural features of bone or, similarly, the deeper research requirements against the broader clinical needs. The considerable potential biological differences between the peripheral appendicular skeleton and the central axial skeleton have to be addressed further. Finally, the relative merits of these sophisticated imaging techniques have to be weighed with respect to their applications as diagnostic procedures requiring high accuracy or reliability on one hand and their monitoring applications requiring high precision or reproducibility on the other. Copyright 2000 S. Karger AG, Basel.

  8. Nestsite selection by male loons leads to sex-biased site familiarity.

    PubMed

    Piper, Walter H; Walcott, Charles; Mager, John N; Spilker, Frank J

    2008-03-01

    1. The concept that animals benefit from gaining familiarity with physical spaces is widespread among ecologists and constitutes a theoretical pillar in studies of territory defence, philopatry and habitat selection. Yet proximate causes and fitness benefits of site familiarity are poorly known. 2. We used data from marked common loons Gavia immer breeding on 98 territories over 14 years to investigate the 'win-stay, lose-switch rule' for nestsite placement (if eggs hatch, reuse nestsite; if predator takes eggs, move nestsite). Males controlled nest placement in this species: pairs used the rule if both members remained the same from the previous nesting attempt or if only the male remained the same but not if only the female remained the same. 3. By means of the nesting rule, male common loons benefited from site familiarity, increasing nesting success by 41% between their first and third years on a territory. In contrast, females exhibited no increase in nesting success with increased territorial tenure. 4. Owing to site familiarity, a male loon competing for a breeding territory faces a considerable 'familiarity deficit' compared with the male breeder already established there. The familiarity deficit probably explains why resident animals often fight hard to retain familiar territories, when challenged, and why animals of many species tend to remain on familiar territories rather than moving when territories of higher intrinsic quality become available nearby.

  9. Application of GIS technology in public health: successes and challenges.

    PubMed

    Fletcher-Lartey, Stephanie M; Caprarelli, Graziella

    2016-04-01

    The uptake and acceptance of Geographic Information Systems (GIS) technology has increased since the early 1990s and public health applications are rapidly expanding. In this paper, we summarize the common uses of GIS technology in the public health sector, emphasizing applications related to mapping and understanding of parasitic diseases. We also present some of the success stories, and discuss the challenges that still prevent a full scope application of GIS technology in the public health context. Geographical analysis has allowed researchers to interlink health, population and environmental data, thus enabling them to evaluate and quantify relationships between health-related variables and environmental risk factors at different geographical scales. The ability to access, share and utilize satellite and remote-sensing data has made possible even wider understanding of disease processes and of their links to the environment, an important consideration in the study of parasitic diseases. For example, disease prevention and control strategies resulting from investigations conducted in a GIS environment have been applied in many areas, particularly in Africa. However, there remain several challenges to a more widespread use of GIS technology, such as: limited access to GIS infrastructure, inadequate technical and analytical skills, and uneven data availability. Opportunities exist for international collaboration to address these limitations through knowledge sharing and governance.

  10. UV Decontamination of MDA Reagents for Single Cell Genomics

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

    Lee, Janey; Tighe, Damon; Sczyrba, Alexander

    2011-03-18

    Single cell genomics, the amplification and sequencing of genomes from single cells, can provide a glimpse into the genetic make-up and thus life style of the vast majority of uncultured microbial cells, making it an immensely powerful and increasingly popular tool. This is accomplished by use of multiple displacement amplification (MDA), which can generate billions of copies of a single bacterial genome producing microgram-range DNA required for shotgun sequencing. Here, we address a key challenge inherent to this approach and propose a solution for the improved recovery of single cell genomes. While DNA-free reagents for the amplification of a singlemore » cell genome are a prerequisite for successful single cell sequencing and analysis, DNA contamination has been detected in various reagents, which poses a considerable challenge. Our study demonstrates the effect of UV irradiation in efficient elimination of exogenous contaminant DNA found in MDA reagents, while maintaining Phi29 activity. Consequently, we also find that increased UV exposure to Phi29 does not adversely affect genome coverage of MDA amplified single cells. While additional challenges in single cell genomics remain to be resolved, the proposed methodology is relatively quick and simple and we believe that its application will be of high value for future single cell sequencing projects.« less

  11. Planning for large epidemics and pandemics: challenges from a policy perspective.

    PubMed

    Jain, Vageesh; Duse, Adriano; Bausch, Daniel G

    2018-05-24

    Less than two decades into the 21st century, the world has already witnessed numerous large epidemics or pandemics. These events have highlighted inadequacies in both national and international capacity for outbreak prevention, detection, and response. Here, we review some of the major challenges from a policy perspective. The most important challenges facing policymakers include financing outbreak preparedness and response in a complex political environment with limited resources, coordinating response efforts among a growing and diverse range of national and international actors, accurately assessing national outbreak preparedness, addressing the shortfall in the global biomedical workforce, building surge capacity of both human and material resources, balancing investments in public health and curative services, building capacity for outbreak-related research and development, and reinforcing measures for infection prevention and control. In recent years, numerous epidemics and pandemics have caused not only considerable loss of life but also billions of dollars of economic loss. Although the events have served as a wake-up call and led to the implementation of relevant policies and counter-measures, such as the Global Health Security Agenda, many questions remain and much work to be done. Wise policies and approaches for outbreak control exist, but will require the political will to implement them.

  12. Regulating the economic evaluation of pharmaceuticals and medical devices: a European perspective.

    PubMed

    Cookson, Richard; Hutton, John

    2003-02-01

    Throughout the developed world, economic evaluation of costly new pharmaceuticals and medical devices became increasingly widespread and systematic during the 1990s. However, serious concerns remain about the validity and relevance of this economic evidence, and about the transparency and accountability of its use in public sector reimbursement decisions. In this article, we summarise current concerns in Europe, based on interviews with European health economists from industry, universities, research institutes and consulting firms. We identify five challenges for European policy-makers, and conclude that there is considerable scope for improving decision-making without damaging incentives to innovate. The challenges are: (1). full publication of the economic evidence used in reimbursement decisions; (2). the redesign of licensing laws to improve the relevance of economic data available at product launch; (3). harmonisation of economic evaluation methodologies; (4). development of methodologies for evaluation of health inequality impacts; and (5). negotiation of price-performance deals to facilitate the use of economic evidence in post-launch pricing review decisions, as information is gathered from studies of product performance in routine use.

  13. Electrical control of single hole spins in nanowire quantum dots.

    PubMed

    Pribiag, V S; Nadj-Perge, S; Frolov, S M; van den Berg, J W G; van Weperen, I; Plissard, S R; Bakkers, E P A M; Kouwenhoven, L P

    2013-03-01

    The development of viable quantum computation devices will require the ability to preserve the coherence of quantum bits (qubits). Single electron spins in semiconductor quantum dots are a versatile platform for quantum information processing, but controlling decoherence remains a considerable challenge. Hole spins in III-V semiconductors have unique properties, such as a strong spin-orbit interaction and weak coupling to nuclear spins, and therefore, have the potential for enhanced spin control and longer coherence times. A weaker hyperfine interaction has previously been reported in self-assembled quantum dots using quantum optics techniques, but the development of hole-spin-based electronic devices in conventional III-V heterostructures has been limited by fabrication challenges. Here, we show that gate-tunable hole quantum dots can be formed in InSb nanowires and used to demonstrate Pauli spin blockade and electrical control of single hole spins. The devices are fully tunable between hole and electron quantum dots, which allows the hyperfine interaction strengths, g-factors and spin blockade anisotropies to be compared directly in the two regimes.

  14. Management of herpesvirus infections.

    PubMed

    Evans, Cariad M; Kudesia, Goura; McKendrick, Mike

    2013-08-01

    Management of human herpesviruses remains a considerable clinical challenge, in part due to their ability to cause both lytic and latent disease. Infection with the Herpesviridae results in lifelong infection, which can reactivate at any time. Control of herpesviruses is by the innate and adaptive immune systems. Herpesviruses must evade the host innate immune system to establish infection. Once infected, the adaptive immune response, primarily CD8(+) T-cells, is crucial in establishing and maintaining latency. Latent herpesviruses are characterised by the presence of viral DNA in infected cells and limited or no viral replication. These characteristics provide a challenge to clinicians and those developing antiviral agents. The scope of this review is two-fold. First, to provide an overview of all antivirals used against herpesviruses, including their mechanism of action, pharmacokinetics, side effects, resistance and clinical uses. And second, to address the management of each of the eight herpesviruses both in the immunocompetent and immunocompromised host, providing evidence for clinical management and therapeutic options, which is important to the clinician engaged in the management of these infections. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  15. The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

    PubMed

    Feikin, Daniel R; Hammitt, Laura L; Murdoch, David R; O'Brien, Katherine L; Scott, J Anthony G

    2017-06-15

    Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  16. Shadows amid sunshine: regulating financial conflicts in medical research.

    PubMed

    Saver, Richard S

    2014-02-01

    Under brand new rules implementing the Physician Payments Sunshine Act (Sunshine Act), a wide range of financial relationships, including many research-related payments, between industry, physicians, and teaching hospitals will be publicly disclosed through comprehensive, standardized payment reporting. The Sunshine Act represents the latest in a series of regulatory attempts to address financial conflicts of interest that may bias research conduct and threaten subject safety. This article summarizes the major aspects of the Sunshine Act affecting medical research, how it interacts with existing laws and policies, and identifies important unresolved issues and implementation challenges that still lie ahead with the rollout of the legislation underway. The Sunshine Act primarily depends on disclosure as a regulatory tool. As such, its long-term impact remains open to question. Disclosure in this context may have limited utility given, among other reasons, uncertainty about who the intended recipients are and their ability to use the information effectively. Apart from the insufficiency of transparency, this article further explores how proportionality, fairness, and accountability considerations make optimal regulation of financial conflicts in medical research quite challenging.

  17. Challenges in the pharmacological management of epilepsy and its causes in the elderly.

    PubMed

    Ferlazzo, Edoardo; Sueri, Chiara; Gasparini, Sara; Aguglia, Umberto

    2016-04-01

    Epilepsy represents the third most common neurological disorders in the elderly after cerebrovascular disorders and dementias. The incidence of new-onset epilepsy peaks in this age group. The most peculiar aetiologies of late-onset epilepsy are stroke, dementia, and brain tumours. However, aetiology remains unknown in about half of the patients. Diagnosis of epilepsy may be challenging due to the frequent absence of ocular witnesses and the high prevalence of seizure-mimics (i.e. transient ischemic attacks, syncope, transient global amnesia or vertigo) in the elderly. The diagnostic difficulties are even greater when patients have cognitive impairment or cardiac diseases. The management of late-onset epilepsy deserves special considerations. The elderly can reach seizure control with low antiepileptic drugs (AEDs) doses, and seizure-freedom is possible in the vast majority of patients. Pharmacological management should take into account pharmacokinetics and pharmacodynamics of AEDs and the frequent occurrence of comorbidities and polytherapy in this age group. Evidences from double-blind and open-label studies indicate lamotrigine, levetiracetam and controlled-release carbamazepine as first line treatment in late-onset epilepsy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Observations of Shock Diffusion and Interactions in Supersonic Freestreams with Counterflowing Jets

    NASA Technical Reports Server (NTRS)

    Daso, Endwell O.; Pritchett, Victor E.; Wang, Ten-See; Blankson, Isiah M.; Auslender, Aaron H.

    2006-01-01

    One of the technical challenges in long-duration space exploration and interplanetary missions is controlled entry and re-entry into planetary and Earth atmospheres, which requires the dissipation of considerable kinetic energy as the spacecraft decelerates and penetrates the atmosphere. Efficient heat load management of stagnation points and acreage heating remains a technological challenge and poses significant risk, particularly for human missions. An innovative approach using active flow control concept is proposed to significantly modify the external flow field about the spacecraft in planetary atmospheric entry and re-entry in order to mitigate the harsh aerothermal environments, and significantly weaken and disperse the shock-wave system to reduce aerothermal loads and wave drag, as well as improving aerodynamic performance. To explore the potential benefits of this approach, we conducted fundamental experiments in a trisonic blow down wind tunnel to investigate the effects of counterflowing sonic and supersonic jets against supersonic freestreams to gain a better understanding of the flow physics of the interactions of the opposing flows and the resulting shock structure.

  19. Neonatal pulmonary physiology.

    PubMed

    Davis, Ryan P; Mychaliska, George B

    2013-11-01

    Managing pulmonary issues faced by both term and preterm infants remains a challenge to the practicing pediatric surgeon. An understanding of normal fetal and neonatal pulmonary development and physiology is the cornerstone for understanding the pathophysiology and treatment of many congenital and acquired problems in the neonate. Progression through the phases of lung development and the transition to postnatal life requires a symphony of complex and overlapping events to work in concert for smooth and successful transition to occur. Pulmonary physiology and oxygen transport in the neonate are similar to older children; however, there are critical differences that are important to take into consideration when treating the youngest of patients. Our understanding of fetal and neonatal pulmonary physiology continues to evolve as the molecular and cellular events governing these processes are better understood. This deeper understanding has helped to facilitate groundbreaking research, leading to improved technology and treatment of term and preterm infants. As therapeutics and research continue to advance, a review of neonatal pulmonary physiology is essential to assist the clinician with his/her management of the wide variety of challenging congenital and acquired pulmonary disease. © 2013 Published by Elsevier Inc.

  20. Pharmacotherapy of anxiety disorders: a critical review

    PubMed Central

    Koen, Nastassja; Stein, Dan J.

    2011-01-01

    Given the enormous contribution of anxiety disorders to the burden of disease, it is key to optimize their prevention and treatment. In this critical review we assess advances in the pharmacotherapy of anxiety disorders, as well as remaining challenges, in recent decades, the field has seen rigorous clinical trial methods to quantify the efficacy and safety of serendipitously discovered agents, more focused development of medications with selective mechanisms of action, and the gradual translation of insights from laboratory research into proof-of-principle clinical trials. On the positive side, a considerable database of studies shows efficacy and relative tolerability of the selective serotonin reuptake inhibitors in the major anxiety disorders, and secondary analyses of such datasets have informed questions such as optimal definition of response and remission, optimal dose and duration, and comparative efficacy of different agents. Significant challenges in the field include barriers to appropriate diagnosis and treatment of anxiety disorders, failure of a significant proportion of patients to respond to first-line pharmacotherapy agents, and a limited database of efficacy or effectiveness studies to guide treatment in such cases. PMID:22275848

  1. Animal models of post-ischemic forced use rehabilitation: methods, considerations, and limitations

    PubMed Central

    2013-01-01

    Many survivors of stroke experience arm impairments, which can severely impact their quality of life. Forcing use of the impaired arm appears to improve functional recovery in post-stroke hemiplegic patients, however the mechanisms underlying improved recovery remain unclear. Animal models of post-stroke rehabilitation could prove critical to investigating such mechanisms, however modeling forced use in animals has proven challenging. Potential problems associated with reported experimental models include variability between stroke methods, rehabilitation paradigms, and reported outcome measures. Herein, we provide an overview of commonly used stroke models, including advantages and disadvantages of each with respect to studying rehabilitation. We then review various forced use rehabilitation paradigms, and highlight potential difficulties and translational problems. Lastly, we discuss the variety of functional outcome measures described by experimental researchers. To conclude, we outline ongoing challenges faced by researchers, and the importance of translational communication. Many stroke patients rely critically on rehabilitation of post-stroke impairments, and continued effort toward progression of rehabilitative techniques is warranted to ensure best possible treatment of the devastating effects of stroke. PMID:23343500

  2. Meta-analysis, complexity, and heterogeneity: a qualitative interview study of researchers' methodological values and practices.

    PubMed

    Lorenc, Theo; Felix, Lambert; Petticrew, Mark; Melendez-Torres, G J; Thomas, James; Thomas, Sian; O'Mara-Eves, Alison; Richardson, Michelle

    2016-11-16

    Complex or heterogeneous data pose challenges for systematic review and meta-analysis. In recent years, a number of new methods have been developed to meet these challenges. This qualitative interview study aimed to understand researchers' understanding of complexity and heterogeneity and the factors which may influence the choices researchers make in synthesising complex data. We conducted interviews with a purposive sample of researchers (N = 19) working in systematic review or meta-analysis across a range of disciplines. We analysed data thematically using a framework approach. Participants reported using a broader range of methods and data types in complex reviews than in traditional reviews. A range of techniques are used to explore heterogeneity, but there is some debate about their validity, particularly when applied post hoc. Technical considerations of how to synthesise complex evidence cannot be isolated from questions of the goals and contexts of research. However, decisions about how to analyse data appear to be made in a largely informal way, drawing on tacit expertise, and their relation to these broader questions remains unclear.

  3. The changing face of cardiovascular disease 2000-2012: An analysis of the world health organisation global health estimates data.

    PubMed

    McAloon, Christopher J; Boylan, Luke M; Hamborg, Thomas; Stallard, Nigel; Osman, Faizel; Lim, Phang B; Hayat, Sajad A

    2016-12-01

    The pattern and global burden of disease has evolved considerably over the last two decades, from primarily communicable, maternal, and perinatal causes to non-communicable disease (NCD). Cardiovascular disease (CVD) has become the single most important and largest cause of NCD deaths worldwide at over 50%. The World Health Organisation (WHO) estimates that 17.6 million people died of CVD worldwide in 2012. Proportionally, this accounts for an estimated 31.43% of global mortality, with ischaemic heart disease (IHD) accounting for approximately 7.4 million deaths, 13.2% of the total. IHD was also the greatest single cause of death in 2000, accounting for an estimated 6.0 million deaths. The global burden of CVD falls, principally, on the low and middle-income (LMI) countries, accounting for over 80% of CVD deaths. Individual populations face differing challenges and each population has unique health burdens, however, CVD remains one of the greatest health challenges both nationally and worldwide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Challenges to Military Operations in Support of U.S. Interests. Volume 2: Main Report

    DTIC Science & Technology

    2008-12-01

    Challenges to Military Operations in Support of U.S. Interests U.S. conventional military capability remains unmatched by any state. As a result, nations...greater importance. PR EF AC E I xiii Preface U.S. conventional military capability remains unmatched by any state. U.S...scope of the study remained robust, presenting the challenge of how to approach the investigation into U.S. capabilities, capability gaps, and

  5. Afterword: Considerations for Future Practice of Assessment and Accountability

    ERIC Educational Resources Information Center

    Bresciani, Marilee J.

    2013-01-01

    This afterword offers challenges and considerations as the assessment movement continues to develop. The author offers some simple considerations for readers to ponder as they advance their evidence-based decision making processes, and encourages others to use these methods within the context of recent neuroscientific evidence that learning and…

  6. Interpreting Microbial Biosynthesis in the Genomic Age: Biological and Practical Considerations

    PubMed Central

    Miller, Ian J.; Chevrette, Marc G.; Kwan, Jason C.

    2017-01-01

    Genome mining has become an increasingly powerful, scalable, and economically accessible tool for the study of natural product biosynthesis and drug discovery. However, there remain important biological and practical problems that can complicate or obscure biosynthetic analysis in genomic and metagenomic sequencing projects. Here, we focus on limitations of available technology as well as computational and experimental strategies to overcome them. We review the unique challenges and approaches in the study of symbiotic and uncultured systems, as well as those associated with biosynthetic gene cluster (BGC) assembly and product prediction. Finally, to explore sequencing parameters that affect the recovery and contiguity of large and repetitive BGCs assembled de novo, we simulate Illumina and PacBio sequencing of the Salinispora tropica genome focusing on assembly of the salinilactam (slm) BGC. PMID:28587290

  7. Are “extreme consumption games” drinking games? Sometimes it's a matter of perspective

    PubMed Central

    Zamboanga, Byron L.; Pearce, Marc W.; Kenney, Shannon R.; Ham, Lindsay S.; Woods, Olivia E.; Borsari, Brian

    2013-01-01

    Drinking games are widespread on college campuses and pose health risks to their players. Although there has been considerable research progress in the college drinking games literature, there does not appear to be a standard definition of the term “drinking games.” Researchers, however, have attempted to classify and categorize drinking games in a systematic manner. For example, one category of drinking games (e.g., chugging, keg stands) is often referred to as consumption or extreme consumption games. Questions remain as to whether or how these types of games align with researchers' definitions of drinking games or the categorization systems advanced by researchers in the field. Potential challenges regarding the definition and categorization of drinking games, particularly with respect to extreme consumption types of games, are discussed. PMID:23968169

  8. Proteomics reveals novel components of the Anopheles gambiae eggshell

    PubMed Central

    Amenya, Dolphine A.; Chou, Wayne; Li, Jianyong; Yan, Guiyun; Gershon, Paul D.; James, Anthony A.; Marinotti, Osvaldo

    2010-01-01

    While genome and transcriptome sequencing has revealed a large number and diversity of Anopheles gambiae predicted proteins, identifying their functions and biosynthetic pathways remains challenging. Applied mass spectrometry based proteomics in conjunction with mosquito genome and transcriptome databases were used to identify 44 proteins as putative components of the eggshell. Among the identified molecules are two vitelline membrane proteins and a group of seven putative chorion proteins. Enzymes with peroxidase, laccase and phenoloxidase activities, likely involved in cross-linking reactions that stabilize the eggshell structure, also were identified. Seven odorant binding proteins were found in association with the mosquito eggshell, although their role has yet to be demonstrated. This analysis fills a considerable gap of knowledge about proteins that build the eggshell of anopheline mosquitoes. PMID:20433845

  9. Towards Establishing Fiscal Legitimacy Through Settled Fiscal Principles in Global Health Financing.

    PubMed

    Waris, Attiya; Latif, Laila Abdul

    2015-12-01

    Scholarship on international health law is currently pushing the boundaries while taking stock of achievements made over the past few decades. However despite the forward thinking approach of scholars working in the field of global health one area remains a stumbling block in the path to achieving the right to health universally: the financing of heath. This paper uses the book Global Health Law by Larry Gostin to reflect and take stock of the fiscal support provided to the right to health from both a global and an African perspective. It then sets out the key fiscal challenges facing global and African health and proposes an innovative solution for consideration: use of the domestic principles of tax to design the global health financing system.

  10. Evidence for a Nematic Phase in La 1.75 Sr 0.25 NiO 4

    DOE PAGES

    Zhong, Ruidan; Winn, Barry L.; Gu, Genda; ...

    2017-04-28

    Determining the nature of electronic states in doped Mott insulators remains a challenging task. In the case of tetragonal La 2 - xSr xNiO 4, the occurrence of diagonal charge and spin stripe order in the ground state is now well established. In contrast, the nature of the high-temperature “disordered” state from which the stripe order develops has long been a subject of controversy, with considerable speculation regarding a polaronic liquid. Following the recent detection of dynamic charge stripes, in this paper we use neutron scattering measurements on an x = 0.25 crystal to demonstrate that the dispersion of themore » charge-stripe excitations is anisotropic. Finally, this observation provides compelling evidence for the presence of electronic nematic order.« less

  11. Freeze-drying of “pearl milk tea”: A general strategy for controllable synthesis of porous materials

    PubMed Central

    Zhou, Yingke; Tian, Xiaohui; Wang, Pengcheng; Hu, Min; Du, Guodong

    2016-01-01

    Porous materials have been widely used in many fields, but the large-scale synthesis of materials with controlled pore sizes, pore volumes, and wall thicknesses remains a considerable challenge. Thus, the controllable synthesis of porous materials is of key general importance. Herein, we demonstrate the “pearl milk tea” freeze-drying method to form porous materials with controllable pore characteristics, which is realized by rapidly freezing the uniformly distributed template-containing precursor solution, followed by freeze-drying and suitable calcination. This general and convenient method has been successfully applied to synthesize various porous phosphate and oxide materials using different templates. The method is promising for the development of tunable porous materials for numerous applications of energy, environment, and catalysis, etc. PMID:27193866

  12. Insect cells-baculovirus system for the production of difficult to express proteins.

    PubMed

    Osz-Papai, Judit; Radu, Laura; Abdulrahman, Wassim; Kolb-Cheynel, Isabelle; Troffer-Charlier, Nathalie; Birck, Catherine; Poterszman, Arnaud

    2015-01-01

    The production of sufficient quantities of homogenous protein not only is an essential prelude for structural investigations but also represents a rate-limiting step for many human functional studies. Although technologies for expression of recombinant proteins and complexes have been improved tremendously, in many cases, protein production remains a challenge and can be associated with considerable investment. This chapter describes simple and efficient protocols for expression screening and optimization of protein production in insect cells using the baculovirus expression system. We describe the procedure, starting from the cloning of a gene of interest into an expression transfer baculovirus vector, followed by generation of the recombinant virus by homologous recombination, evaluation of protein expression, and scale-up. Handling of insect cell cultures and preparation of bacmid for co-transfection are also detailed.

  13. Cleaner cooking solutions to achieve health, climate, and economic cobenefits.

    PubMed

    Anenberg, Susan C; Balakrishnan, Kalpana; Jetter, James; Masera, Omar; Mehta, Sumi; Moss, Jacob; Ramanathan, Veerabhadran

    2013-05-07

    Nearly half the world's population must rely on solid fuels such as biomass (wood, charcoal, agricultural residues, and animal dung) and coal for household energy, burning them in inefficient open fires and stoves with inadequate ventilation. Household solid fuel combustion is associated with four million premature deaths annually; contributes to forest degradation, loss of habitat and biodiversity, and climate change; and hinders social and economic progress as women and children spend hours every day collecting fuel. Several recent studies, as well as key emerging national and international efforts, are making progress toward enabling wide-scale household adoption of cleaner and more efficient stoves and fuels. While significant challenges remain, these efforts offer considerable promise to save lives, improve forest sustainability, slow climate change, and empower women around the world.

  14. Conjugated Polymers for Flexible Energy Harvesting and Storage.

    PubMed

    Zhang, Zhitao; Liao, Meng; Lou, Huiqing; Hu, Yajie; Sun, Xuemei; Peng, Huisheng

    2018-03-01

    Since the discovery of conjugated polymers in the 1970s, they have attracted considerable interest in light of their advantages of having a tunable bandgap, high electroactivity, high flexibility, and good processability compared to inorganic conducting materials. The above combined advantages make them promising for effective energy harvesting and storage, which have been widely studied in recent decades. Herein, the key advancements in the use of conjugated polymers for flexible energy harvesting and storage are reviewed. The synthesis, structure, and properties of conjugated polymers are first summarized. Then, their applications in flexible polymer solar cells, thermoelectric generators, supercapacitors, and lithium-ion batteries are described. The remaining challenges are then discussed to highlight the future direction in the development of conjugated polymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Trematode diversity in freshwater fishes of the Globe I: 'Old World'.

    PubMed

    Scholz, Tomáš; Besprozvannykh, Vladimir V; Boutorina, Tamara E; Choudhury, Anindo; Cribb, Thomas H; Ermolenko, Alexey V; Faltýnková, Anna; Shedko, Marina B; Shimazu, Takeshi; Smit, Nico J

    2016-03-01

    In this paper, we review, continent by continent, the trematode fauna of freshwater fishes of the 'Old World', a vast area consisting of the Palaearctic, Ethiopian, Oriental and Australasian zoogeographical regions. Knowledge of this fauna is highly uneven and clearly incomplete for almost all regions, sometimes dramatically so. Although the biggest problem remains the completion of the 'first pass' of alpha taxonomy, there are in addition great problems relating to biogeography and elucidation of life-cycles. For the latter, molecular data, i.e. matching DNA sequences of larval stages and corresponding adults, may represent a powerful tool that should be used in future studies. Another challenging problem represents the existence of cryptic species and, in particular, considerable decrease of experts in taxonomy and life-cycles of trematodes.

  16. Surgery for obstructed defecation syndrome-is there an ideal technique

    PubMed Central

    Riss, Stefan; Stift, Anton

    2015-01-01

    Obstructive defecation syndrome (ODS) is a common disorder with a considerable impact on the quality of life of affected patients. Surgery for ODS remains a challenging topic. There exists a great variety of operative techniques to treat patients with ODS. According to the surgeon’s preference the approach can be transanal, transvaginal, transperineal or transabdominal. All techniques have its advantages and disadvantages. Notably, high evidence based studies are significantly lacking in literature, thus making accurate assessments difficult. Careful patient’s selection is crucial to achieve optimal functional results. It is mandatory to assess not only defecation disorders but also evaluate overall pelvic floor symptoms, such as fecal incontinence and urinary disorders for choosing an appropriate and tailored strategy. Radiological investigation is essential but may not explain complaints of every patient. PMID:25574075

  17. Maggot therapy in treatment of a complex hand injury complicated by mycotic infection.

    PubMed

    Bohac, M; Cambal, M; Zamborsky, R; Takac, P; Fedeles, J

    2015-01-01

    Complex injuries of the hand remain a therapeutic challenge for surgeons. We present the case of a male who suffered a devastating injury of the hand caused by a conveyor belt. The patient developed a progressive Absidia corymbifera infection of the affected soft tissues. Initial treatments with serial surgical debridement and topical and intravenous itraconazole were unsuccessful in eliminating the infection. We decided to use maggot debridement therapy in a new special design to debride all necrotic, devitalized tissue and preserve only healthy tissue and functioning structures. This maneuverer followed by negative pressure therapy allowed progressive healing. In such complex hand injuries, maggot debridement combined with negative pressure therapy could be considered to achieve effective and considerable results, although future functional morbidity may occur (Fig. 4, Ref. 18).

  18. Design principles for therapeutic angiogenic materials

    NASA Astrophysics Data System (ADS)

    Briquez, Priscilla S.; Clegg, Lindsay E.; Martino, Mikaël M.; Gabhann, Feilim Mac; Hubbell, Jeffrey A.

    2016-01-01

    Despite extensive research, pro-angiogenic drugs have failed to translate clinically, and therapeutic angiogenesis, which has potential in the treatment of various cardiovascular diseases, remains a major challenge. Physiologically, angiogenesis — the process of blood-vessel growth from existing vasculature — is regulated by a complex interplay of biophysical and biochemical cues from the extracellular matrix (ECM), angiogenic factors and multiple cell types. The ECM can be regarded as the natural 3D material that regulates angiogenesis. Here, we leverage knowledge of ECM properties to derive design rules for engineering pro-angiogenic materials. We propose that pro-angiogenic materials should be biomimetic, incorporate angiogenic factors and mimic cooperative interactions between growth factors and the ECM. We highlight examples of material designs that demonstrate these principles and considerations for designing better angiogenic materials.

  19. Three-dimensional vectorial multifocal arrays created by pseudo-period encoding

    NASA Astrophysics Data System (ADS)

    Zeng, Tingting; Chang, Chenliang; Chen, Zhaozhong; Wang, Hui-Tian; Ding, Jianping

    2018-06-01

    Multifocal arrays have been attracting considerable attention recently owing to their potential applications in parallel optical tweezers, parallel single-molecule orientation determination, parallel recording and multifocal multiphoton microscopy. However, the generation of vectorial multifocal arrays with a tailorable structure and polarization state remains a great challenge, and reports on multifocal arrays have hitherto been restricted either to scalar focal spots without polarization versatility or to regular arrays with fixed spacing. In this work, we propose a specific pseudo-period encoding technique to create three-dimensional (3D) vectorial multifocal arrays with the ability to manipulate the position, polarization state and intensity of each focal spot. We experimentally validated the flexibility of our approach in the generation of 3D vectorial multiple spots with polarization multiplicity and position tunability.

  20. End User Evaluations

    NASA Astrophysics Data System (ADS)

    Jay, Caroline; Lunn, Darren; Michailidou, Eleni

    As new technologies emerge, and Web sites become increasingly sophisticated, ensuring they remain accessible to disabled and small-screen users is a major challenge. While guidelines and automated evaluation tools are useful for informing some aspects of Web site design, numerous studies have demonstrated that they provide no guarantee that the site is genuinely accessible. The only reliable way to evaluate the accessibility of a site is to study the intended users interacting with it. This chapter outlines the processes that can be used throughout the design life cycle to ensure Web accessibility, describing their strengths and weaknesses, and discussing the practical and ethical considerations that they entail. The chapter also considers an important emerging trend in user evaluations: combining data from studies of “standard” Web use with data describing existing accessibility issues, to drive accessibility solutions forward.

  1. Evidence for a Nematic Phase in La 1.75 Sr 0.25 NiO 4

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

    Zhong, Ruidan; Winn, Barry L.; Gu, Genda

    Determining the nature of electronic states in doped Mott insulators remains a challenging task. In the case of tetragonal La 2 - xSr xNiO 4, the occurrence of diagonal charge and spin stripe order in the ground state is now well established. In contrast, the nature of the high-temperature “disordered” state from which the stripe order develops has long been a subject of controversy, with considerable speculation regarding a polaronic liquid. Following the recent detection of dynamic charge stripes, in this paper we use neutron scattering measurements on an x = 0.25 crystal to demonstrate that the dispersion of themore » charge-stripe excitations is anisotropic. Finally, this observation provides compelling evidence for the presence of electronic nematic order.« less

  2. Improving integration and coordination of funding, technical assistance, and reporting/data collection: recommendations from CDC and USAPI stakeholders.

    PubMed

    Ka'opua, Lana Sue I; White, Susan F; Rochester, Phyllis F; Holden, Debra J

    2011-03-01

    Current US Federal funding mechanisms may foster program silos that disable sharing of resources and information across programs within a larger system of public health services. Such silos present challenges to USAPI communities where human resources, health infrastructure, and health financing are limited. Integrative and coordinated approaches have been recommended. The CDC Pacific Islands Integration and Coordination project was initiated by the CDC Division of Cancer Prevention and Control (DCPC). The project aim was to identify ways for the CDC to collaborate with the USAPI in improving CDC activities and processes related to chronic disease. This article focuses on recommendations for improving coordination and integration in three core areas of health services programming: funding, program reporting/data collection and analysis, and technical assistance. Preliminary information on challenges and issues relevant to the core areas was gathered through site visits, focus groups, key informant interviews, and other sources. This information was used by stakeholder groups from the CDC and the USAPI to develop recommendations in the core programming areas. Recommendations generated at the CDC and USAPI stakeholder meetings were prepared into a single set of recommendations and stakeholders reviewed the document for accuracy prior to its dissemination to CDC's National Center for Chronic Disease Prevention and Health Promotion programs management and staff. Key recommendations, include: (1) consideration of resources and other challenges unique to the USAPI when reviewing funding applications, (2) consideration of ways to increase flexibility in USAPI use of program funds, (3) dedication of funding and human resources for technical assistance, (4) provision of opportunities for capacity-building across programs and jurisdictions, (5) consideration of ways to more directly link program reporting with technical assistance. This project provided a unique opportunity for CDC and USAPI stakeholders to share diverse perspectives on challenges to public health programs in the USAPI. Despite diverse experiences, the final set of recommendations reflected a high level of concordance between USAPI and CDC stakeholders. Recommendations have informed or reinforced actions initiated by the DCPC, including the dedication of funds for leadership institutes aimed at enhancing USAPI capacity for sustainable, integrated regional and jurisdictional cancer control infrastructure. Such efforts are an important beginning, but more remains to be done. Indicated is the need for continuous dialogue and collaboration. While this project focused on the USAPI, our results may be relevant to those interested in inter-organizational collaborations, medically underserved areas, public health services programs, and community-based participatory approaches.

  3. Challenges Facing Teachers New to Working in Schools Overseas

    ERIC Educational Resources Information Center

    Halicioglu, Margaret L.

    2015-01-01

    This article considers the potential challenges facing teachers moving abroad for the first time, both professional challenges in their school and personal challenges in their private life. It suggests that such teachers embarking on a professional adventure overseas would benefit from careful consideration of the kind of school they will thrive…

  4. Hurricanes and Climate: the U.S. CLIVAR Working Group on Hurricanes

    NASA Technical Reports Server (NTRS)

    Walsh, Kevin; Camargo, Suzana J.; Vecchi, Gabriel A.; Daloz, Anne Sophie; Elsner, James; Emanuel, Kerry; Horn, Michael; Lim, Young-Kwon; Roberts, Malcolm; Patricola, Christina; hide

    2015-01-01

    While a quantitative climate theory of tropical cyclone formation remains elusive, considerable progress has been made recently in our ability to simulate tropical cyclone climatologies and understand the relationship between climate and tropical cyclone formation. Climate models are now able to simulate a realistic rate of global tropical cyclone formation, although simulation of the Atlantic tropical cyclone climatology remains challenging unless horizontal resolutions finer than 50 km are employed. The idealized experiments of the Hurricane Working Group of U.S. CLIVAR, combined with results from other model simulations, have suggested relationships between tropical cyclone formation rates and climate variables such as mid-tropospheric vertical velocity. Systematic differences are shown between experiments in which only sea surface temperature is increases versus experiments where only atmospheric carbon dioxide is increased, with the carbon dioxide experiments more likely to demonstrate a decrease in numbers. Further experiments are proposed that may improve our understanding of the relationship between climate and tropical cyclone formation, including experiments with two-way interaction between the ocean and the atmosphere and variations in atmospheric aerosols.

  5. The origin of animals: Can molecular clocks and the fossil record be reconciled?

    PubMed

    Cunningham, John A; Liu, Alexander G; Bengtson, Stefan; Donoghue, Philip C J

    2017-01-01

    The evolutionary emergence of animals is one of the most significant episodes in the history of life, but its timing remains poorly constrained. Molecular clocks estimate that animals originated and began diversifying over 100 million years before the first definitive metazoan fossil evidence in the Cambrian. However, closer inspection reveals that clock estimates and the fossil record are less divergent than is often claimed. Modern clock analyses do not predict the presence of the crown-representatives of most animal phyla in the Neoproterozoic. Furthermore, despite challenges provided by incomplete preservation, a paucity of phylogenetically informative characters, and uncertain expectations of the anatomy of early animals, a number of Neoproterozoic fossils can reasonably be interpreted as metazoans. A considerable discrepancy remains, but much of this can be explained by the limited preservation potential of early metazoans and the difficulties associated with their identification in the fossil record. Critical assessment of both records may permit better resolution of the tempo and mode of early animal evolution. © 2016 The Authors BioEssays Published by WILEY Periodicals, Inc.

  6. A comprehensive review on cold work of AISI D2 tool steel

    NASA Astrophysics Data System (ADS)

    Abdul Rahim, Mohd Aidil Shah bin; Minhat, Mohamad bin; Hussein, Nur Izan Syahriah Binti; Salleh, Mohd Shukor bin

    2017-11-01

    As a common material in mould and die application, AISI D2 cold work tool steel has proven to be a promising chosen material in the industries. However, challenges remain in using AISI D2 through a modified version with a considerable progress having been made in recent years. This paper provides a critical review of the original as-cast AISI D2 cold work tool steel up to the modified version. The main purpose is to develop an understanding of current modified tool steel trend; the machinability of AISI D2 (drilling, milling, turning, grinding and EDM/WEDM; and the microstructure evolution and mechanical properties of these cold work tool steels due to the presence of alloy materials in the steel matrix. The doping of rare earth alloy element, new steel fabrication processes, significant process parameter in machinability and surface treatment shows that there have been few empirical investigations into these cold work tool steel alloys. This study has discovered that cold work tool steel will remain to be explored in order to survive in the steel industries.

  7. “One Health” or three? Publication silos among the One Health disciplines

    USGS Publications Warehouse

    Manlove, Kezia; Walker, Josephine G; Craft, Meggan E.; Huyvaert, Kathryn P.; Joseph, Maxwell B.; Miller, Ryan S.; Nol, Pauline; Patyk, Kelly A.; O'Brian, Daniel; Walsh, Daniel P.; Cross, Paul C.

    2016-01-01

    The One Health initiative is a global effort fostering interdisciplinary collaborations to address challenges in human, animal, and environmental health. While One Health has received considerable press, its benefits remain unclear because its effects have not been quantitatively described. We systematically surveyed the published literature and used social network analysis to measure interdisciplinarity in One Health studies constructing dynamic pathogen transmission models. The number of publications fulfilling our search criteria increased by 14.6% per year, which is faster than growth rates for life sciences as a whole and for most biology subdisciplines. Surveyed publications clustered into three communities: one used by ecologists, one used by veterinarians, and a third diverse-authorship community used by population biologists, mathematicians, epidemiologists, and experts in human health. Overlap between these communities increased through time in terms of author number, diversity of co-author affiliations, and diversity of citations. However, communities continue to differ in the systems studied, questions asked, and methods employed. While the infectious disease research community has made significant progress toward integrating its participating disciplines, some segregation—especially along the veterinary/ecological research interface—remains.

  8. Magnetic Ghosts: Mineral Magnetic Measurements On Roman and Anglo-saxon Graves

    NASA Astrophysics Data System (ADS)

    Linford, N.

    The location of inhumations, in the absence of ferrous grave goods, often presents a considerable challenge to archaeological geophysics given the small physical size of the features and the slight contrast between the fill of the grave and the surround- ing subsoil. Even during excavation, the identification of graves may be complicated where site conditions do not favour the preservation of human skeletal remains and often only a subtle soil stain is likely to survive. A recent initiative in the United King- dom has seen the formation of the Buried Organic Matter Decomposition Integrated with Elemental Status (BODIES) research group, to examine the decomposition of organic artefacts in ancient graves with respect to localised changes in pH, redox po- tential and nutrient status. This paper presents initial results from a limited mineral magnetic study of two grave sites in an attempt to ascertain whether the decomposi- tion of organic remains may lead to a detectable magnetic signature within the soil. Results from a series of isothermal, hysteresis and magneto-thermal experiments will be presented together with surface magnetometer and topsoil susceptibility surveys.

  9. “One Health” or Three? Publication Silos Among the One Health Disciplines

    PubMed Central

    Craft, Meggan E.; Joseph, Maxwell B.; Miller, Ryan S.; Nol, Pauline; Patyk, Kelly A.; O’Brien, Daniel; Walsh, Daniel P.; Cross, Paul C.

    2016-01-01

    The One Health initiative is a global effort fostering interdisciplinary collaborations to address challenges in human, animal, and environmental health. While One Health has received considerable press, its benefits remain unclear because its effects have not been quantitatively described. We systematically surveyed the published literature and used social network analysis to measure interdisciplinarity in One Health studies constructing dynamic pathogen transmission models. The number of publications fulfilling our search criteria increased by 14.6% per year, which is faster than growth rates for life sciences as a whole and for most biology subdisciplines. Surveyed publications clustered into three communities: one used by ecologists, one used by veterinarians, and a third diverse-authorship community used by population biologists, mathematicians, epidemiologists, and experts in human health. Overlap between these communities increased through time in terms of author number, diversity of co-author affiliations, and diversity of citations. However, communities continue to differ in the systems studied, questions asked, and methods employed. While the infectious disease research community has made significant progress toward integrating its participating disciplines, some segregation—especially along the veterinary/ecological research interface—remains. PMID:27100532

  10. Supercritical carbon dioxide-assisted rapid synthesis of few-layer black phosphorus for hydrogen peroxide sensing.

    PubMed

    Yan, Shancheng; Wang, Bojun; Wang, Zhulan; Hu, Dong; Xu, Xin; Wang, Junzhuan; Shi, Yi

    2016-06-15

    Solutions with large-scale dispersions of 2D black phosphorus (BP), often referred to as phosphorene, are obtained through solvent exfoliation. But, rapid phosphorene synthesis remains a challenge. Furthermore, although the chemical sensing capability of BP-based sensors has been theoretically predicted, its experimental verification remains lacking. In this study, we demonstrate the use of supercritical carbon dioxide-assisted rapid synthesis (5h) of few-layer BP. In addition, we construct a non-enzymatic hydrogen peroxide (H2O2) sensor based on few-layer BP for the first time to utilize BP degradation under ambient conditions. The proposed H2O2 sensor exhibits a considerably lower detection limit of 1 × 10(-7) M compared with the general detection limit of 1 × 10(-7) M-5 × 10(-5)M via electrochemical methods. Overall, the results of this study will not only expand the coverage of BP research but will also identify the important sensing characteristics of BP. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Studying Sexual Aggression: A Review of the Evolution and Validity of Laboratory Paradigms

    PubMed Central

    Davis, Kelly Cue; George, William H.; Nagayama Hall, Gordon C.; Parrott, Dominic J.; Tharp, Andra Teten; Stappenbeck, Cynthia A.

    2018-01-01

    Objective Researchers have endeavored for decades to develop and implement experimental assessments of sexual aggression and its precursors to capitalize on the many scientific advantages offered by laboratory experiments, such as rigorous control of key variables and identification of causal relationships. The purpose of this review is to provide an overview of and commentary on the evolution of these laboratory-based methods. Conclusions To date, two primary types of sexual aggression laboratory studies have been developed: those that involve behavioral analogues of sexual aggression and those that assess postulated precursors to sexually aggressive behavior. Although the study of sexual aggression in the laboratory is fraught with methodological challenges, validity concerns, and ethical considerations, advances in the field have resulted in greater methodological rigor, more precise dependent measures, and improved experimental validity, reliability, and realism. Because highly effective sexual aggression prevention strategies remain elusive, continued laboratory-based investigation of sexual aggression coupled with translation of critical findings to the development and modification of sexual aggression prevention programs remains an important task for the field. PMID:29675289

  12. Technical considerations in the psychotherapy of traumatized individuals: a psychoanalytic perspective.

    PubMed

    Nayar, Monisha C

    2008-03-01

    This paper addresses two specific aspects of clinical technique in the treatment of traumatized individuals. The first aspect involves the creation of a safe holding environment as an essential step for the emergence of trauma-related memories and the containment of the affects accompanying them. Such scenarios may appear in the clinical material only through the workings of "procedural memory." It is therefore important to contain and gradually decipher repetitive patterns of behavior and feelings of shame, guilt and rage that go with them. The second aspect examines the challenges such work poses to the analyst's containing capacities, credulousness and even his or her reality testing within a clinical situation. The resulting instability of the analyst's work ego can make it hard for him or her to remain vigilant yet empathic, and emotionally attuned but analytically skeptical. The analyst's flexibility to be utilized as a transference object, developmental object and self-object remains a critical determinant of the treatment outcome under such circumstances. The paper provides clinical material to illustrate these two aspects of clinical technique.

  13. Cellular regeneration strategies for macular degeneration: past, present and future.

    PubMed

    Chichagova, Valeria; Hallam, Dean; Collin, Joseph; Zerti, Darin; Dorgau, Birthe; Felemban, Majed; Lako, Majlinda; Steel, David H

    2018-05-01

    Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.

  14. Health Technology Assessment, International Reference Pricing, and Budget Control Tools from China's Perspective: What Are the Current Developments and Future Considerations?

    PubMed

    Koh, Liling; Glaetzer, Christoph; Chuen Li, Shu; Zhang, Meng

    2016-05-01

    China is investing considerably in health care reforms to address issues in its health care system. An example is access to innovative drugs, which remains challenging because it is largely dependent on patient self-pay. Recognizing this, the government has invested considerably in its basic medical insurance. As health care expenditure increases, there are growing concerns on budget control. Several health policy tools have been discussed recently such as health technology assessment, international reference pricing, and hospital budget control tools, which can be viewed as addressing the affordability concerns of the government budget. China has also listed her health outcomes goals in "Healthy China 2020" initiative. This article aimed to discuss the "fit-for-purpose" of these tools to address budget concerns and support China in reaching her health outcomes goals. The findings are informed by a panel discussion at ISPOR Asia Pacific 2014, literature review, and authors' experience. This review looks at the current developments in China and the considerations and implications for using these tools by drawing experiences from countries where they are used. These tools are generally used in countries with advanced health care systems. China's health care spending is still below that of countries with advanced health care systems and below World Health Organization recommendation. China has not yet reached the "critical mass" necessary for the effective use of these tools. As China continues its health care reforms, increase in health care spending to balance the health needs of the population would be key. Copyright © 2015. Published by Elsevier Inc.

  15. Pandemic Influenza and Pregnancy: An Opportunity to Reassess Maternal Bioethics

    PubMed Central

    Beigi, Richard H.

    2009-01-01

    Large-scale infectious epidemics present the medical community with numerous medical and ethical challenges. Recent attention has focused on the likelihood of an impending influenza pandemic caused by the H5N1 virus. Pregnant women in particular present policymakers with great challenges to planning for such a public health emergency. By recognizing the specific considerations needed for this population, we can preemptively address the issues presented by infectious disease outbreaks. We reviewed the important ethical challenges presented by pregnant women and highlighted the considerations for all vulnerable groups when planning for a pandemic at both the local and the national level. PMID:19461111

  16. Shape transitions during clathrin-induced endocytosis

    NASA Astrophysics Data System (ADS)

    Kumar, Gaurav; Sain, Anirban

    2016-12-01

    Endocytosis is among the most common transport mechanisms which cells employ to receive macromolecules, the so-called cargo, from its extra cellular environment. Clathrin-mediated endocytosis (CME), in particular, involves the cytoplasmic protein clathrin which induces formation and internalization of clathrin-coated membrane buds that contain extra-cellular cargo. Decades of experimental work have established that the morphology of the clathrin coat evolves with time and induces its curvature on the membrane bud; but energetics of the process remain unclear. Recent experiments by Avinoam et al. [Science 348, 1369 (2015), 10.1126/science.aaa9555] reported that the area of the clathrin coat remains fixed while its curvature increases with time and also the clathrin molecules in the coat turn over rapidly. We show that these observations challenge existing models of coated membrane bud formation. We analyze their data to bring out certain features consistent with the underlying lattice structure of the coat. We hypothesize that membrane curvature inhibits clathrin deposition and propose a kinetic model that explains the area distribution of clathrin coats. We also show that their data on shape evolution of the coated membrane bud can be approximately understood from simple geometric considerations. However, the energetics of the coat formation which controls the kinetics of the process remains a puzzle.

  17. Methodological difficulties in the conduct of neuroepidemiological studies in low- and middle-income countries.

    PubMed

    Bharucha, Nadir; Odermatt, Peter; Preux, Pierre-Marie

    2014-01-01

    The majority of people with epilepsy (PWE) live in low- and middle-income countries (LMICs). However, they remain largely untreated and the bulk of resources are used to treat patients in the developed world. This disparity constitutes a challenge for neuroepidemiological studies on a global scale. In the past, several studies have focused on diverse populations in disparate countries at various periods of time and for particular purposes. The specificity of different contexts and circumstances makes it difficult to analyse PWE as a group either qualitatively or quantitatively. Such methodological limitations are further complicated by a lack of logistical support. There is a lack of interest in conducting studies, which results in inadequate funding and, in addition, there is the considerable challenge of publishing research reports from LMICs in peer-reviewed international journals. This paper focuses on methodological problems related to studies in LMICs and attempts to give the reasons for their limitations using epilepsy as an example. Regional conditions and environmental factors must be given careful consideration in the research design because of the importance of understanding the challenges of living in these environments. There are further limitations to the successful implementation of studies. Existing information on epilepsy is often not readily accessible; there is a lack of census data, and migratory patterns into cities make enumeration and sampling even more challenging. As there is usually no well-developed healthcare system a door-to-door screening process is often the only way to identify those with convulsive epilepsy. The questionnaire and study design should preferably be adapted from standardized protocols, and pre-tested and validated in local conditions. Systematic reviews and meta-analyses of studies in LMICs can provide data on the burden, risk factors, treatment and outcome of epilepsy only if the primary studies used are properly conducted using uniform and comparable methodology. The use of consistent replicable neuroepidemiological methods in primary studies and systematic reviews enable reduction of the treatment gap and better epilepsy care. © 2013 S. Karger AG, Basel.

  18. Applications of satellite 'hyper-sensing' in Chinese agriculture: Challenges and opportunities

    NASA Astrophysics Data System (ADS)

    Onojeghuo, Alex Okiemute; Blackburn, George Alan; Huang, Jingfeng; Kindred, Daniel; Huang, Wenjiang

    2018-02-01

    Ensuring adequate food supplies to a large and increasing population continues to be the key challenge for China. Given the increasing integration of China within global markets for agricultural products, this issue is of considerable significance for global food security. Over the last 50 years, China has increased the production of its staple crops mainly by increasing yield per unit land area. However, this has largely been achieved through inappropriate agricultural practices, which have caused environmental degradation, with deleterious consequences for future agricultural productivity. Hence, there is now a pressing need to intensify agriculture in China using practices that are environmentally and economically sustainable. Given the dynamic nature of crops over space and time, the use of remote sensing technology has proven to be a valuable asset providing end-users in many countries with information to guide sustainable agricultural practices. Recently, the field has experienced considerable technological advancements reflected in the availability of 'hyper-sensing' (high spectral, spatial and temporal) satellite imagery useful for monitoring, modelling and mapping of agricultural crops. However, there still remains a significant challenge in fully exploiting such technologies for addressing agricultural problems in China. This review paper evaluates the potential contributions of satellite 'hyper-sensing' to agriculture in China and identifies the opportunities and challenges for future work. We perform a critical evaluation of current capabilities in satellite 'hyper-sensing' in agriculture with an emphasis on Chinese sensors. Our analysis draws on a series of in-depth examples based on recent and on-going projects in China that are developing 'hyper-sensing' approaches for (i) measuring crop phenology parameters and predicting yields; (ii) specifying crop fertiliser requirements; (iii) optimising management responses to abiotic and biotic stress in crops; (iv) maximising yields while minimising water use in arid regions; (v) large-scale crop/cropland mapping; and (vi) management zone delineation. The paper concludes with a synthesis of these application areas in order to define the requirements for future research, technological innovation and knowledge exchange in order to deliver yield sustainability in China.

  19. Differing levels of clinical evidence: exploring communication challenges in shared decision making. Introduction.

    PubMed

    Smith, Quentin W; Street, Richard L; Volk, Robert J; Fordis, Michael

    2013-02-01

    The near ubiquitous access to information is transforming the roles and relationships among clinical professionals, patients, and their care givers in nearly all aspects of healthcare. Informed patients engage their physicians in conversations about their conditions, options and the tradeoffs among diagnostic and therapeutic benefits and harms. The processes of care today increasingly and explicitly integrate exploration of patient values and preferences as patients and clinicians jointly engage in reaching decisions about care. The informed patient of today who can understand and use scientific information can participate as an equal partner with her clinician. Others with beliefs or educational, cultural, or literacy backgrounds that pose challenges to comprehending and applying evidence may face disenfranchisement. These barriers are significant enough, even in the face of certainty of evidence, that clinicians and investigators have given much thought to how best to engage all patients in decision making. However, barriers remain, as most decision making must occur in settings where uncertainty, if not considerable uncertainty, accompanies any statement of what we know. In September 2011, health care and health communication experts came together in Rockville, Maryland under the auspices of the Agency for Healthcare Research and Quality (AHRQ) John M. Eisenberg Center for Clinical Decisions and Communications Science Annual Meeting to explore the challenges of differing levels of evidence in promoting shared decisions and to propose strategies for going forward in addressing these challenges. Eight scholarly papers emerged, and with this introductory article, comprise this special issue of Medical Care Research and Review.

  20. The Challenge and Challenging of Childhood Studies? Learning from Disability Studies and Research with Disabled Children

    ERIC Educational Resources Information Center

    Tisdall, E. Kay M.

    2012-01-01

    Childhood studies have argued for the social construction of childhood, respecting children and childhood in the present, and recognising children's agency and rights. Such perspectives have parallels to, and challenges for, disability studies. This article considers such parallels and challenges, leading to a (re)consideration of research claims…

  1. Pharmacogenomic Challenges in Cardiovascular Diseases: Examples of Drugs and Considerations for Future Integration in Clinical Practice.

    PubMed

    Chatelin, Jerome; Stathopoulou, Maria G; Arguinano, Alex-Ander A; Xie, Ting; Visvikis-Siest, Sophie

    2017-01-01

    Even if cardiovascular disease (CVD) drugs are supported by high level proofs, the results of CVD treatment present great disparities: there are still patients dying with supposed optimal treatment, patients facing adverse events and CVD remains the primary cause of death in the world. Pharmacogenomics is the basis of personalisation of the treatment able to allow higher medication success rates. In this review, we will present detailed examples of CVD drugs to highlight the complexity of this challenging field and we will discuss novel concepts that should be considered for a fastest integration of pharmacogenomics in clinical practice of CVD. Areas Covered: The complexity of pharmacogenetics and pharmacogenomics of CVD drugs are presented though examples of medications such as statins, with a focus on their effectiveness and adverse effects. Expert Opinion: The application of personalised medicine in the CVD medical practice requires the study of human genome with regard to drugs pharmacokinetics, pharmacodynamics, interactions and tolerance profile. The existing state -of-the-art of CVD drugs gives hopes for a future revolution in the drug development that will maximise cardiovascular patients benefit while decreasing their risks for adverse effects. Article Highlights Box: • Coronary heart disease (CHD) remains the first cause of death worldwide. • Cardiovascular treatment has a significant percentage of insufficient efficacy, poor tolerance and compliance. • Predicting the response to therapy while diminishing the side effects is the basis of personalised medicine; pharmacogenomics is leading towards this direction. • The response to CVD therapy and side effects are in the heart of CVD pharmacogenomics and significant progress has been noted. • The application of pharmacogenomics in the CVD medical practice is facing many methodological, technical, ethical, behavioral and financial issues, while cost-effectiveness is the main prerequisite. • The consideration of gene × gene × environment interactions and the inclusion of "omics" data in pharmacogenomic studies of CVD drugs will facilitate the generation of reliable results and will promote tailored treatments and new strategies of drug research and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Environmental reporting and accounting in Australia: progress, prospects and research priorities.

    PubMed

    van Dijk, Albert; Mount, Richard; Gibbons, Philip; Vardon, Michael; Canadell, Pep

    2014-03-01

    Despite strong demand for information to support the sustainable use of Australia's natural resources and conserve environmental values and despite considerable effort and investment, nation-wide environmental data collection and analysis remains a substantially unmet challenge. We review progress in producing national environmental reports and accounts, identify challenges and opportunities, and analyse the potential role of research in addressing these. Australia's low and concentrated population density and the short history since European settlement contribute to the lack of environmental data. There are additional factors: highly diverse data requirements and standards, disagreement on information priorities, poorly measurable management objectives, lack of coordination, over-reliance on researchers and businesses for data collection, lack of business engagement, and short-term, project-based activities. New opportunities have arisen to overcome some of these challenges: enhanced monitoring networks, standardisation, data management and modelling, greater commitment to share and integrate data, community monitoring, increasing acceptance of environmental and sustainability indicators, and progress in environmental accounting practices. Successes in generating climate, water and greenhouse gas information appear to be attributable to an unambiguous data requirement, considerable investment, and legislative instruments that enhance data sharing and create a clearly defined role for operational agencies. Based on the analysis presented, we suggest six priorities for research: (1) common definitions and standards for information that address management objectives, (2) ecological measures that are scalable from local to national level, (3) promotion of long-term data collection and reporting by researchers, (4) efficient satellite and sensor network technologies and data analysis methods, (5) environmental modelling approaches that can reconcile multiple data sources, and (6) experimental accounting to pursue consistent, credible and relevant information structures and to identify new data requirements. Opportunities exist to make progress in each of these areas and help secure a more sustainable future. Copyright © 2014. Published by Elsevier B.V.

  3. Accounting for the influence of vegetation and landscape improves model transferability in a tropical savannah region

    NASA Astrophysics Data System (ADS)

    Gao, Hongkai; Hrachowitz, Markus; Sriwongsitanon, Nutchanart; Fenicia, Fabrizio; Gharari, Shervan; Savenije, Hubert H. G.

    2016-10-01

    Understanding which catchment characteristics dominate hydrologic response and how to take them into account remains a challenge in hydrological modeling, particularly in ungauged basins. This is even more so in nontemperate and nonhumid catchments, where—due to the combination of seasonality and the occurrence of dry spells—threshold processes are more prominent in rainfall runoff behavior. An example is the tropical savannah, the second largest climatic zone, characterized by pronounced dry and wet seasons and high evaporative demand. In this study, we investigated the importance of landscape variability on the spatial variability of stream flow in tropical savannah basins. We applied a stepwise modeling approach to 23 subcatchments of the Upper Ping River in Thailand, where gradually more information on landscape was incorporated. The benchmark is represented by a classical lumped model (FLEXL), which does not account for spatial variability. We then tested the effect of accounting for vegetation information within the lumped model (FLEXLM), and subsequently two semidistributed models: one accounting for the spatial variability of topography-based landscape features alone (FLEXT), and another accounting for both topographic features and vegetation (FLEXTM). In cross validation, each model was calibrated on one catchment, and then transferred with its fitted parameters to the remaining catchments. We found that when transferring model parameters in space, the semidistributed models accounting for vegetation and topographic heterogeneity clearly outperformed the lumped model. This suggests that landscape controls a considerable part of the hydrological function and explicit consideration of its heterogeneity can be highly beneficial for prediction in ungauged basins in tropical savannah.

  4. Platelet utilization: a Canadian Blood Services research and development symposium.

    PubMed

    Webert, Kathryn E; Alam, Asim Q; Chargé, Sophie B; Sheffield, William P

    2014-04-01

    Considerable progress has been made in recent years in understanding platelet biology and in strengthening the clinical evidence base around platelet transfusion thresholds and appropriate platelet dosing. Platelet alloimmunization rates have also declined. Nevertheless, controversies and uncertainties remain that are relevant to how these products can best be used for the benefit of platelet transfusion recipients. Platelets are unique among the blood products directly derived from whole blood or apheresis donations in requiring storage, with shaking, at ambient temperature. Storage is accordingly constrained between the need to limit the growth of any microbes in the product and the need to minimize losses in platelet function associated with storage. Proteomic and genomic approaches are being applied to the platelet storage lesion. Platelet inventory management is made challenging by these constraints. Although bacterial screening has enhanced the safety of platelet transfusions, pathogen reduction technology may offer further benefits. Continuing clinical investigations are warranted to understand the value of transfusing platelets prophylactically or only in response to bleeding in different patient groups and how best to manage the most grievously injured trauma patients. Patients refractory to platelet transfusions also require expert clinical management. The engineering of platelet substitute products is an active area of research, but considerable hurdles remain before any clinical uses may be contemplated. Roles for platelets in biological areas distinct from hemostasis are also emerging. Platelet utilization is variably affected by all of the above factors, by demographic changes, by new medications, and by new patient care approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Time for action: key considerations for implementing social accountability in the education of health professionals.

    PubMed

    Ventres, William; Boelen, Charles; Haq, Cynthia

    2017-09-12

    Within health professional education around the world, there exists a growing awareness of the professional duty to be socially responsible, being attentive to the needs of all members of communities, regions, and nations, especially those who disproportionately suffer from the adverse influence of social determinants. However, much work still remains to progress beyond such good intentions. Moving from contemplation to action means embracing social accountability as a key guiding principle for change. Social accountability means that health institutions attend to improving the performance of individual practitioners and health systems by directing educational and practice interventions to promote the health of all the public and assessing the systemic effects of these interventions. In this Reflection, the authors (1) review the reasons why health professional schools and their governing bodies should codify, in both curricular and accreditation standards, norms of excellence in social accountability, (2) present four considerations crucial to successfully implementing this codification, and (3) discuss the challenges such changes might entail. The authors conclude by noting that in adopting socially accountable criteria, schools will need to expand their philosophical scope to recognize social accountability as a vitally important part of their institutional professional identity.

  6. ECS Law & Education Center Footnotes. No. 3.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO. Law and Education Center.

    Commentary and advice in four legal areas are offered in this newsletter on educational law. First, the document outlines preventive legal review for public educators in four basic steps, including anticipation of legal challenges, evaluation of the challenges' legal merits, consideration of the policy issues raised by potential challenges, and…

  7. Bridging the Gap: The Challenges of Employing Entrepreneurial Processes within University Settings

    ERIC Educational Resources Information Center

    Wardale, Dorothy; Lord, Linley

    2016-01-01

    In Australia and elsewhere, universities face increasing pressure to improve research output and quality, particularly through partnerships with industry. This raises interesting challenges for academic staff with considerable industry experience who are "new" to academe. Some of these challenges were faced by the authors who have been…

  8. Considerations of Alloy 617 Application in the Gen IV Nuclear Reactor Systems - Part II: Metallurgical Property Challenges

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

    Ren, Weiju

    2010-01-01

    Alloy 617 is currently considered as a leading candidate material for high temperature components in the Gen IV Nuclear Reactor Systems. Because of the unprecedented severe working conditions beyond its commercial service experience required by the Gen IV systems, the alloy faces various challenges in both mechanical and metallurgical properties. Following a previous paper discussing the mechanical property challenges, this paper is focused on the challenges and issues in metallurgical properties of the alloy for the intended nuclear application. Considerations are given in details about its metallurgical stability and aging evolution, aging effects on mechanical properties, potential Co hazard, andmore » internal oxidation. Some research and development activities are suggested with discussions on viability to satisfy the Gen IV Nuclear Reactor System needs.« less

  9. Treatment of Early Onset Schizophrenia: Recent Trends, Challenges and Future Considerations

    PubMed Central

    Vyas, Nora S.; Gogtay, Nitin

    2012-01-01

    Early onset schizophrenia (onset before adulthood) is a rare, severe, and chronic form of schizophrenia. The clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis. This is a brief, condensed review of current treatment strategies for the early onset population highlighting the need for novel treatment strategies for these generally treatment-refractory cases. Based on the current literature, second-generation antipsychotics remain the mainstay of treatment, although current medications provide suboptimal response at best. Based on the adult literature, combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy. Indeed, early detection, identification of relevant biomarkers, coupled with advancing knowledge of the neurochemical and neuroanatomic pathways may help design informed and novel treatment strategies. PMID:22485097

  10. Human exposure limits to hypergolic fuels

    NASA Technical Reports Server (NTRS)

    Garcia, H. D.; James, J. T.; Limero, T. F.

    1992-01-01

    Over the past four decades, many studies have been conducted on the toxicities of the rocket propellants hydrazine (HZ) and monomethylhydrazine (MH). Numerous technical challenges have made it difficult to unambiguously interpret the results of these studies, and there is considerable divergence between results obtained by different investigators on the inhalation concentrations (MAC's) for each toxic effect inducible by exposure to hypergolic fuels in spacecraft atmospheres, NASA undertook a critical review of published and unpublished investigations on the toxicities of these compounds. The current state of the art practices for similar studies. While many questions remain unanswered, MAC's were determined using the best available data for a variety of toxic endpoints for potential continuous exposure durations ranging from 1 hour to 180 days. Spacecraft MAC's (SMAC's) were set for each compound based on the most sensitive toxic endpoint at each exposure duration.

  11. Social Responsibility and Healthcare in Finland.

    PubMed

    Ahola-Launonen, Johanna

    2016-07-01

    This article examines current trends and prospects in Finnish healthcare literature and discussion. The Finnish healthcare system was long considered to manifest an equal, universal, and solidaristic welfare scheme. However, recent data reveals structural inequalities in access to healthcare that result in health differences among socioeconomic groups. The political will aims at tackling these inequalities, but the ideological trend toward responsibilization of the individual taking place across political spheres elsewhere in Europe creates potential challenges to this goal. The applications of this trend have a theoretical background in the responsibility-sensitive egalitarian-or luck egalitarian-tradition. The theory, which is unfit for real-life policy applications, has explicit appeal in considerations aiming at the responsibilization of the individual within the healthcare sector. It remains to be seen in which direction the Finnish welfare schemes will continue to develop.

  12. Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease

    PubMed Central

    Hoban, Megan D.; Bauer, Daniel E.

    2016-01-01

    Effective medical management for sickle cell disease (SCD) remains elusive. As a prevalent and severe monogenic disorder, SCD has been long considered a logical candidate for gene therapy. Significant progress has been made in moving toward this goal. These efforts have provided substantial insight into the natural regulation of the globin genes and illuminated challenges for genetic manipulation of the hematopoietic system. The initial γ-retroviral vectors, next-generation lentiviral vectors, and novel genome engineering and gene regulation approaches each share the goal of preventing erythrocyte sickling. After years of preclinical studies, several clinical trials for SCD gene therapies are now open. This review focuses on progress made toward achieving gene therapy, the current state of the field, consideration of factors that may determine clinical success, and prospects for future development. PMID:26758916

  13. TOPICAL REVIEW: The physics, biophysics and technology of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wilson, Brian C.; Patterson, Michael S.

    2008-05-01

    Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components—light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT.

  14. Climate-chemical interactions and effects of changing atmospheric trace gases

    NASA Technical Reports Server (NTRS)

    Ramanathan, V.; Callis, L.; Cess, R.; Hansen, J.; Isaksen, I.

    1987-01-01

    The paper considers trace gas-climate effects including the greenhouse effect of polyatomic trace gases, the nature of the radiative-chemical interactions, and radiative-dynamical interactions in the stratosphere, and the role of these effects in governing stratospheric climate change. Special consideration is given to recent developments in the investigations of the role of oceans in governing the transient climate responses, and a time-dependent estimate of the potential trace gas warming from the preindustrial era to the early 21st century. The importance of interacting modeling and observational efforts is emphasized. One of the problems remaining on the observational front is the lack of certainty in current estimates of the rate of growth of CO, O3, and NOx; the primary challenge is the design of a strategy that will minimize the sampling errors.

  15. Unsolved matters in leprosy: a descriptive review and call for further research.

    PubMed

    Franco-Paredes, Carlos; Rodriguez-Morales, Alfonso J

    2016-05-21

    Leprosy, a chronic mycobacterial infection caused by Mycobacterium leprae, is an infectious disease that has ravaged human societies throughout millennia. This ancestral pathogen causes disfiguring cutaneous lesions, peripheral nerve injury, ostearticular deformity, limb loss and dysfunction, blindness and stigma. Despite ongoing efforts in interrupting leprosy transmission, large numbers of new cases are persistently identified in many endemic areas. Moreover, at the time of diagnosis, most newly identified cases have considerable neurologic disability. Many challenges remain in our understanding of the epidemiology of leprosy including: (a) the precise mode and route of transmission; (b) the socioeconomic, environmental, and behavioral factors that promote its transmission; and (c) strategies to achieve early diagnosis and prevent neurologic impairment to reduce the large burden of disability among newly identified cases; and among those who endure long-term disability in spite of completing multidrug therapy.

  16. Medical and surgical management of perianal Crohn’s disease

    PubMed Central

    Adegbola, Samuel O.; Pisani, Anthea; Sahnan, Kapil; Tozer, Phil; Ellul, Pierre; Warusavitarne, Janindra

    2018-01-01

    Crohn’s disease is increasingly thought to encompass multiple possible phenotypes. Perianal manifestations account for one such phenotype and represent an independent disease modifier. In its more severe form, perianal Crohn’s disease confers a higher risk of a severe and disabling disease course, relapses, hospital admissions and operations. This, in turn, imposes a considerable burden and disability on patients. Identification of the precise manifestation is important, as management is nuanced, with both medical and surgical components, and is best undertaken in a multidisciplinary setting for both diagnosis and ongoing treatment. The introduction of biologic medication has heralded a significant addition to the management of fistulizing perianal Crohn’s disease in particular, albeit with modest results. It remains a very challenging condition to treat and further work is required to optimize management in this group of patients. PMID:29507460

  17. Understanding the Experience of Stroke: A Mixed-Method Research Agenda

    PubMed Central

    Clarke, Philippa

    2009-01-01

    The use of both quantitative and qualitative strategies to examine a single research question has been a subject of considerable controversy and still remains a largely uncommon practice in the sociology of health and illness. Yet, when seeking to understand the meaning of a chronic disabling condition in later life from a social psychological perspective, a mixed-method approach is likely to provide the most comprehensive picture. This article provides an overview of the usefulness and appropriateness of a mixed-method approach to understanding the stroke experience. I comment on the current state of research on the experience of stroke, including epistemological and ontological orientations. Using real data examples, I address paradigmatic assumptions, methods of integration, as well as challenges and pitfalls in integrating methods. I conclude by considering future directions in this field of research. PMID:19386828

  18. Assessment of Montana road weather information system : final report

    DOT National Transportation Integrated Search

    2017-01-01

    Weather presents considerable challenges to highway agencies both in terms of safety and operations. State transportation agencies have developed road weather information systems (RWIS) to address such challenges. Road weather information has been us...

  19. Planning for planetary protection : challenges beyond Mars

    NASA Technical Reports Server (NTRS)

    Belz, Andrea P.; Cutts, James A.

    2006-01-01

    This document summarizes the technical challenges to planetary protection for these targets of interest and outlines some of the considerations, particularly at the system level, in designing an appropriate technology investment strategy for targets beyond Mars.

  20. Fidelity considerations in translational research: Eating As Treatment - a stepped wedge, randomised controlled trial of a dietitian delivered behaviour change counselling intervention for head and neck cancer patients undergoing radiotherapy.

    PubMed

    Beck, Alison Kate; Baker, Amanda; Britton, Ben; Wratten, Chris; Bauer, Judith; Wolfenden, Luke; Carter, Gregory

    2015-10-15

    The confidence with which researchers can comment on intervention efficacy relies on evaluation and consideration of intervention fidelity. Accordingly, there have been calls to increase the transparency with which fidelity methodology is reported. Despite this, consideration and/or reporting of fidelity methods remains poor. We seek to address this gap by describing the methodology for promoting and facilitating the evaluation of intervention fidelity in The EAT (Eating As Treatment) project: a multi-site stepped wedge randomised controlled trial of a dietitian delivered behaviour change counselling intervention to improve nutrition (primary outcome) in head and neck cancer patients undergoing radiotherapy. In accordance with recommendations from the National Institutes of Health Behaviour Change Consortium Treatment Fidelity Workgroup, we sought to maximise fidelity in this stepped wedge randomised controlled trial via strategies implemented from study design through to provider training, intervention delivery and receipt. As the EAT intervention is designed to be incorporated into standard dietetic consultations, we also address unique challenges for translational research. We offer a strong model for improving the quality of translational findings via real world application of National Institutes of Health Behaviour Change Consortium recommendations. Greater transparency in the reporting of behaviour change research is an important step in improving the progress and quality of behaviour change research. ACTRN12613000320752 (Date of registration 21 March 2013).

  1. Clinical and practical considerations in the pharmacologic management of narcolepsy.

    PubMed

    Thorpy, Michael J; Dauvilliers, Yves

    2015-01-01

    Despite published treatment recommendations and the availability of approved and off-label pharmacologic therapies for narcolepsy, the clinical management of this incurable, chronic neurologic disorder remains challenging. While treatment is generally symptomatically driven, decisions regarding which drug(s) to use need to take into account a variety of factors that may affect adherence, efficacy, and tolerability. Type 1 narcolepsy (predominantly excessive daytime sleepiness with cataplexy) or type 2 narcolepsy (excessive daytime sleepiness without cataplexy) may drive treatment decisions, with consideration given either to a single drug that targets multiple symptoms or to multiple drugs that each treat a specific symptom. Other drug-related characteristics that affect drug choice are dosing regimens, tolerability, and potential drug-drug interactions. Additionally, the patient should be an active participant in treatment decisions, and the main symptomatic complaints, treatment goals, psychosocial setting, and use of lifestyle substances (ie, alcohol, nicotine, caffeine, and cannabis) need to be discussed with respect to treatment decisions. Although there is a lack of narcolepsy-specific instruments for monitoring therapeutic effects, clinically relevant subjective and objective measures of daytime sleepiness (eg, Epworth Sleepiness Scale and Maintenance of Wakefulness Test) can be used to provide guidance on whether treatment goals are being met. These considerations are discussed with the objective of providing clinically relevant recommendations for making treatment decisions that can enhance the effective management of patients with narcolepsy. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Research ethics in the post-genomic era.

    PubMed

    Vähäkangas, Kirsi

    2013-08-01

    New high-throughput 'omics techniques are providing exciting opportunities in clinical medicine and toxicology, especially in the development of biomarkers. In health science research there are traditional ethical considerations that are reasonably obvious, like balancing health benefits and health risks, autonomy mainly pursued by informed consent, and protecting privacy. Epidemiological studies applying new large-scale approaches (e.g., high-throughput or high-content methods and global studies that utilize biobanking of samples and produce large-scale datasets) present new challenges that call for re-evaluation of standard ethical considerations. In this context, assessment of the ethics underlying study designs, bioinformatics, and statistics applied in the generation and clinical translation of research results should also be considered. Indeed, there are ethical considerations in the research process itself, in research objectives and how research is pursued (e.g., which methodologies are selected and how they are carried out). Maintaining research integrity is critical, as demonstrated by the relatively frequent retraction of scientific papers following violations of good scientific practice. Abiding by the laws is necessary but not sufficient for good research ethics, which is and remains in the hands of the scientific community at the level of both individual scientists and organizations. Senior scientists are responsible for the transfer of research tradition to the next generation of scientists through education, mentorship, and setting an example by their own behavior, as well as by creating systems in institutions that support good research ethics. Copyright © 2013 Wiley Periodicals, Inc.

  3. Evaluation of carbon nanotube probes in critical dimension atomic force microscopes.

    PubMed

    Choi, Jinho; Park, Byong Chon; Ahn, Sang Jung; Kim, Dal-Hyun; Lyou, Joon; Dixson, Ronald G; Orji, Ndubuisi G; Fu, Joseph; Vorburger, Theodore V

    2016-07-01

    The decreasing size of semiconductor features and the increasing structural complexity of advanced devices have placed continuously greater demands on manufacturing metrology, arising both from the measurement challenges of smaller feature sizes and the growing requirement to characterize structures in more than just a single critical dimension. For scanning electron microscopy, this has resulted in increasing sophistication of imaging models. For critical dimension atomic force microscopes (CD-AFMs), this has resulted in the need for smaller and more complex tips. Carbon nanotube (CNT) tips have thus been the focus of much interest and effort by a number of researchers. However, there have been significant issues surrounding both the manufacture and use of CNT tips. Specifically, the growth or attachment of CNTs to AFM cantilevers has been a challenge to the fabrication of CNT tips, and the flexibility and resultant bending artifacts have presented challenges to using CNT tips. The Korea Research Institute for Standards and Science (KRISS) has invested considerable effort in the controlled fabrication of CNT tips and is collaborating with the National Institute of Standards and Technology on the application of CNT tips for CD-AFM. Progress by KRISS on the precise control of CNT orientation, length, and end modification, using manipulation and focused ion beam processes, has allowed us to implement ball-capped CNT tips and bent CNT tips for CD-AFM. Using two different generations of CD-AFM instruments, we have evaluated these tip types by imaging a line/space grating and a programmed line edge roughness specimen. We concluded that these CNTs are capable of scanning the profiles of these structures, including re-entrant sidewalls, but there remain important challenges to address. These challenges include tighter control of tip geometry and careful optimization of scan parameters and algorithms for using CNT tips.

  4. Salt, time, and metaphor: examining norms in scientific culture

    NASA Astrophysics Data System (ADS)

    Brady, Anna G.

    2017-06-01

    As has been widely discussed, the National Research Council's (NRC) current policy in United States education advocates supporting students toward acquiring skills to engage in scientific practices. NRC policy also suggests that supporting students in the practices of science may require different approaches than what is required for supporting student engagement with scientific content. Further, acquiring skills in scientific practices is not limited to gaining proficiency in utilizing tools that support scientific inquiry: students must also understand how to interpret information generated from such tools. These tools of scientific practices are embedded within scientific culture, which from Sewell's perspective, is comprised of both practice and semiotic code (symbols and meanings). To become scientifically literate students must learn to utilize this code in practice. Author Germà Garcia-Belmonte identified one example of learning to utilize the semiotic code in scientific practice and considers challenges faced by undergraduate physics and engineering students within that context. Garcia-Belmonte observes students struggle to interpret symbols and meaning (the visual display generated) while engaging in practice (utilizing an oscilloscope) and posits that two, culturally bound, competing, linguistic metaphors of time may be the cause. Ultimately, however, the author does not explore beyond hypotheses. Although his theory may be correct, the paper serves as a reminder of the responsibility we have to students. As educators, it is useful and beneficial to make observations and develop theories surrounding why our students struggle. However, in addition to theorizing on why, for example, a particular scientific norm might present challenges for our students, we must remain mindful that challenges may not be uniform and may vary considerably according to students' culture(s). Engaging with students and soliciting specific information regarding the challenges they face allows us, as educators, to both examine whether students' reported challenges align or conflict with our own perceptions of those challenges, and subsequently devise and test methods toward supporting students in overcoming their challenges.

  5. Why primary care practices should become digital health information hubs for their patients.

    PubMed

    Baird, Aaron; Nowak, Samantha

    2014-11-25

    Two interesting health care trends are currently occurring: 1) patient-facing technologies, such as personal health records, patient portals, and mobile health apps, are being adopted at rapid rates, and 2) primary care, which includes family practice, is being promoted as essential to reducing health care costs and improving health care outcomes. While these trends are notable and commendable, both remain subject to significant fragmentation and incentive misalignments, which has resulted in significant data coordination and value generation challenges. In particular, patient-facing technologies designed to increase care coordination, often fall prey to the very digital fragmentation issues they are supposed to overcome. Additionally, primary care providers are treating patients that may have considerable health information histories, but generating a single view of such multi-source data is nearly impossible. We contribute to this debate by proposing that primary care practices become digital health information hubs for their patients. Such hubs would offer health data coordination in a medically professional setting with the benefits of expert, trustworthy advice coupled with active patient engagement. We acknowledge challenges including: costs, information quality and provenance, willingness-to-share information and records, willingness-to-use (by both providers and patients), primary care scope creep, and determinations of technical and process effectiveness. Even with such potential challenges, we strongly believe that more debate is needed on this topic prior to full implementation of various health information technology incentives and reform programs currently being designed and enacted throughout the world. Ultimately, if we do not provide a meaningful way for the full spectrum of health information to be used by both providers and patients, especially early in the health care continuum, effectively improving health outcomes may remain elusive. We view the primary care practice as a central component of digital information coordination, especially when considering the current challenges of digital health information fragmentation. Given these fragmentation issues and the emphasis on primary care as central to improving health and lower overall health care costs, we suggest that primary care practices should embrace their evolving role and should seek to become digital health information hubs for their patients.

  6. Driving and flying with epilepsy.

    PubMed

    Drazkowski, Joseph F

    2007-07-01

    Transportation issues in industrialized nations play an important role in the lives of most citizens. The acts of flying and driving, especially in the United States, intersect with many peoples' lives on almost a daily basis. Although some larger cities have modern and efficient public transportation systems, many do not, thus placing considerable responsibility on the individual to manage their own transportation needs. A person with epilepsy faces considerable challenges when it comes to transportation. Defining these challenges and understanding how to deal with the person with epilepsy and transportation issues is the focus of this article.

  7. Brain death in Islamic ethico-legal deliberation: challenges for applied Islamic bioethics.

    PubMed

    Padela, Aasim I; Arozullah, Ahsan; Moosa, Ebrahim

    2013-03-01

    Since the 1980s, Islamic scholars and medical experts have used the tools of Islamic law to formulate ethico-legal opinions on brain death. These assessments have varied in their determinations and remain controversial. Some juridical councils such as the Organization of Islamic Conferences' Islamic Fiqh Academy (OIC-IFA) equate brain death with cardiopulmonary death, while others such as the Islamic Organization of Medical Sciences (IOMS) analogize brain death to an intermediate state between life and death. Still other councils have repudiated the notion entirely. Similarly, the ethico-legal assessments are not uniform in their acceptance of brain-stem or whole-brain criteria for death, and consequently their conceptualizations of, brain death. Within the medical literature, and in the statements of Muslim medical professional societies, brain death has been viewed as sanctioned by Islamic law with experts citing the aforementioned rulings. Furthermore, health policies around organ transplantation and end-of-life care within the Muslim world have been crafted with consideration of these representative religious determinations made by transnational, legally-inclusive, and multidisciplinary councils. The determinations of these councils also have bearing upon Muslim clinicians and patients who encounter the challenges of brain death at the bedside. For those searching for 'Islamically-sanctioned' responses that can inform their practice, both the OIC-IFA and IOMS verdicts have palpable gaps in their assessments and remain clinically ambiguous. In this paper we analyze these verdicts from the perspective of applied Islamic bioethics and raise several questions that, if answered by future juridical councils, will better meet the needs of clinicians and bioethicists. © 2011 Blackwell Publishing Ltd.

  8. Snow in Earth System Models: Recent Progress and Future Challenges

    NASA Astrophysics Data System (ADS)

    Clark, M. P.; Slater, A. G.

    2016-12-01

    Snow is the most variable of terrestrial boundary conditions. Some 50 million km^2 of the Northern Hemisphere typically sees periods of accumulation and ablation in the annual cycle. The wonderous properties of snow, such as high albedo, thermal insulation and its ability to act as a water store make it an integral part of the global climate system. Earliest inclusions of snow within climate models were simple adjustments to albedo and a moisture store. Modern Earth Syetem Models now represent snow through a myriad of model architectures and parameterizations that span a broad range of complexity. Understanding the impacts of modeling decisions upon simulation of snow and other Earth System components (either directly or via feedbacks) is an ongoing area of research. Snow models are progressing with multi-layer representations and capabilities such as complex albedo schemes that include contaminants. While considerable advances have been made, numerous challenges also remain. Simply getting a grasp on the mass of snow (seasonal or permanent) has proved more difficult than expected over the past 30 years. Snow interactions with vegetation has improved but the details of vegetation masking and emergence are still limited. Inclusion of blowing snow processes, in terms of transport and sublimation, is typically rare and sublimation remains a difficult quantity to measure. Contemplation of snow crystal form within models and integration with radiative transfer schemes for better understanding of full spectrum interations (from UV to long microwave) may simultaneously advance simulation and remote sensing. A series of international modeling experiments and directed field campaigns are planned in the near future with the aim of pushing our knowledge forward.

  9. Concurrent malaria and typhoid fever in the tropics: the diagnostic challenges and public health implications.

    PubMed

    Uneke, C J

    2008-06-01

    Malaria and typhoid fever still remain diseases of major public health importance in the tropics. Individuals in areas endemic for both the diseases are at substantial risk of contracting both these diseases, either concurrently or an acute infection superimposed on a chronic one. The objective of this report was to systematically review scientific data from studies conducted in the tropics on concurrent malaria and typhoid fever within the last two decades (1987-2007), to highlight the diagnostic challenges and the public health implications. Using the MedLine Entrez-PubMed search, relevant publications were identified for the review via the key words Malaria and Typhoid fever, which yielded 287 entries as of January 2008. Most of the studies reviewed expressed concern that poor diagnosis continues to hinder effective control of concurrent malaria and typhoid fever in the tropics due to: non-specific clinical presentation of the diseases; high prevalence of asymptomatic infections; lack of resources and insufficient access to trained health care providers and facilities; and widespread practice of self-treatment for clinically suspected malaria or typhoid fever. There were considerably higher rates of concurrent malaria and typhoid fever by Widal test compared to the bacteriological culture technique. Although culture technique remains the gold standard in typhoid fever diagnosis, Widal test is still of significant diagnostic value provided judicious interpretation of the test is made against a background of pertinent information. Malaria could be controlled through interventions to minimize human-vector contact, while improved personal hygiene, targeted vaccination campaigns and intensive community health education could help to control typhoid fever in the tropics.

  10. Jumping genes: Genomic ballast or powerhouse of biological diversification.

    PubMed

    Choudhury, Rimjhim Roy; Parisod, Christian

    2017-09-01

    Studying hybridization has the potential to elucidate challenging questions in evolutionary biology such as the nature of adaptive genetic variation and reproductive isolation. A growing body of work highlights that the merging of divergent genomes goes beyond the reshuffling of standing variation from related species and promotes mutations (Abbott et al., ). However, to what extent such genome instability generates evolutionary significant variation remains largely elusive. In this issue of Molecular Ecology, Dennenmoser et al. () report considerable dynamics of transposable elements (TEs) in a recent invasive fish species of hybrid origin (Cottus; Figure ). It adds to the recent examples from plants to support TE-specific genome variation following hybridization. Insights from early, as well as established, hybrids are largely coherent with increased TE activity, and this fish system thus represents an inspiring opportunity to further address the possible association between genome dynamics and "rapid evolution of hybrid species." This work based on genome (re)sequencing contrasts with prior transcriptomics or PCR-based studies of TEs and illustrates how unprecedented amount of information promises a better understanding of the multiple patterns of variation across eukaryotic genomes; provided that we get the better of methodological advances. As discussed here, unbiased assessment of TE variation from genome surveys indeed remains a challenge precluding firm conclusions to be reached about the evolutionary significance of TEs. Despite methodological and conceptual developments that appear necessary to unambiguously uncover the unexplored iceberg below the known tip, the role of coding genes vs. TEs in promoting adaptation and speciation might be clarified in a not so remote future. © 2017 John Wiley & Sons Ltd.

  11. Experimental intramammary inoculation with Mycoplasma bovis in vaccinated and unvaccinated cows: effect on milk production and milk quality.

    PubMed Central

    Boothby, J T; Jasper, D E; Thomas, C B

    1986-01-01

    The effect of vaccination on milk production was evaluated in vaccinated and control cows experimentally challenged in two of four quarters with live Mycoplasma bovis. During the first three weeks after experimental challenge, six of eight unchallenged quarters on vaccinated cows and seven of eight unchallenged quarters on control cows became infected. Most of these quarters secreted normal milk, with negative California Mastitis Test scores and maintained normal milk production throughout most of the study (although some quarters on control cows remained infected). All challenged quarters became infected, had strong California Mastitis Test reactions, and had a drastic (greater than 85%) loss in milk production. Thereafter, four of eight challenged quarters on control cows remained infected, had mostly positive California Mastitis Test scores, produced mostly normal-appearing milk, and recovered some productive capabilities. By the end of the study no M. bovis could be recovered from challenged quarters on vaccinated cows and the milk appeared mostly normal. The California Mastitis Test scores on these quarters, however, remained elevated and milk production remained very low. PMID:3756674

  12. Launch Vehicle Selection and the Implementation of the Soil Moisture Active Passive Mission

    NASA Technical Reports Server (NTRS)

    Sherman, Sarah; Waydo, Peter; Eremenko, Alexander

    2016-01-01

    Soil Moisture Active Passive (SMAP) is a NASA-developed Earth science satellite currently mapping the soil moisture content and freeze/thaw state of Earth's land mass from a 685km, near-polar, sun-synchronous orbit. It was launched on January 31, 2015 from Vandenberg AFB upon a Delta II 7320 launch vehicle. Due to external considerations, SMAP's launch vehicle selection remained an open item until Project Critical Design Review (CDR). Thus, certain key aspects of the spacecraft design had to accommodate a diverse range of candidate launch vehicle environments, performance envelopes, interfaces and operational scenarios. Engineering challenges stemmed from two distinct scenarios: decisions that had to be made prior to launch vehicle selection to accommodate all possible outcomes, and post-selection changes constrained by schedule and the existing spacecraft configuration. The effects of the timing of launch vehicle selection reached virtually every aspect of the Observatory's design and development. Physical environments, mass allocations, material selections, propulsion system performance, dynamic response, launch phase and mission planning, overall size and configuration, and of course all interfaces to the launch vehicle were heavily dependent on this outcome. This paper will discuss the resolution of these technical challenges.

  13. Beyond Compliance Checking: A Situated Approach to Visual Research Ethics.

    PubMed

    Lenette, Caroline; Botfield, Jessica R; Boydell, Katherine; Haire, Bridget; Newman, Christy E; Zwi, Anthony B

    2018-03-19

    Visual research methods like photography and digital storytelling are increasingly used in health and social sciences research as participatory approaches that benefit participants, researchers, and audiences. Visual methods involve a number of additional ethical considerations such as using identifiable content and ownership of creative outputs. As such, ethics committees should use different assessment frameworks to consider research protocols with visual methods. Here, we outline the limitations of ethics committees in assessing projects with a visual focus and highlight the sparse knowledge on how researchers respond when they encounter ethical challenges in the practice of visual research. We propose a situated approach in relation to visual methodologies that encompasses a negotiated, flexible approach, given that ethical issues usually emerge in relation to the specific contexts of individual research projects. Drawing on available literature and two case studies, we identify and reflect on nuanced ethical implications in visual research, like tensions between aesthetics and research validity. The case studies highlight strategies developed in-situ to address the challenges two researchers encountered when using visual research methods, illustrating that some practice implications are not necessarily addressed using established ethical clearance procedures. A situated approach can ensure that visual research remains ethical, engaging, and rigorous.

  14. Gene Editing of Microalgae: Scientific Progress and Regulatory Challenges in Europe

    PubMed Central

    Spicer, Andrew

    2018-01-01

    It is abundantly clear that the development of gene editing technologies, represents a potentially powerful force for good with regard to human and animal health and addressing the challenges we continue to face in a growing global population. This now includes the development of approaches to modify microalgal strains for potential improvements in productivity, robustness, harvestability, processability, nutritional composition, and application. The rapid emergence and ongoing developments in this area demand a timely review and revision of the current definitions and regulations around genetically modified organisms (GMOs), particularly within Europe. Current practices within the EU provide exemptions from the GMO directives for organisms, including crop plants and micro-organisms that are produced through chemical or UV/radiation mutagenesis. However, organisms generated through gene editing, including microalgae, where only genetic changes in native genes are made, remain currently under the GMO umbrella; they are, as such, excluded from practical and commercial opportunities in the EU. In this review, we will review the advances that are being made in the area of gene editing in microalgae and the impact of regulation on commercial advances in this area with consideration to the current regulatory framework as it relates to GMOs including GM microalgae in Europe. PMID:29509719

  15. Genetic Inventory Task Final Report. Volume 2

    NASA Technical Reports Server (NTRS)

    Venkateswaran, Kasthuri; LaDuc, Myron T.; Vaishampayan, Parag

    2012-01-01

    Contaminant terrestrial microbiota could profoundly impact the scientific integrity of extraterrestrial life-detection experiments. It is therefore important to know what organisms persist on spacecraft surfaces so that their presence can be eliminated or discriminated from authentic extraterrestrial biosignatures. Although there is a growing understanding of the biodiversity associated with spacecraft and cleanroom surfaces, it remains challenging to assess the risk of these microbes confounding life-detection or sample-return experiments. A key challenge is to provide a comprehensive inventory of microbes present on spacecraft surfaces. To assess the phylogenetic breadth of microorganisms on spacecraft and associated surfaces, the Genetic Inventory team used three technologies: conventional cloning techniques, PhyloChip DNA microarrays, and 454 tag-encoded pyrosequencing, together with a methodology to systematically collect, process, and archive nucleic acids. These three analysis methods yielded considerably different results: Traditional approaches provided the least comprehensive assessment of microbial diversity, while PhyloChip and pyrosequencing illuminated more diverse microbial populations. The overall results stress the importance of selecting sample collection and processing approaches based on the desired target and required level of detection. The DNA archive generated in this study can be made available to future researchers as genetic-inventory-oriented technologies further mature.

  16. Gene Editing of Microalgae: Scientific Progress and Regulatory Challenges in Europe.

    PubMed

    Spicer, Andrew; Molnar, Attila

    2018-03-06

    It is abundantly clear that the development of gene editing technologies, represents a potentially powerful force for good with regard to human and animal health and addressing the challenges we continue to face in a growing global population. This now includes the development of approaches to modify microalgal strains for potential improvements in productivity, robustness, harvestability, processability, nutritional composition, and application. The rapid emergence and ongoing developments in this area demand a timely review and revision of the current definitions and regulations around genetically modified organisms (GMOs), particularly within Europe. Current practices within the EU provide exemptions from the GMO directives for organisms, including crop plants and micro-organisms that are produced through chemical or UV/radiation mutagenesis. However, organisms generated through gene editing, including microalgae, where only genetic changes in native genes are made, remain currently under the GMO umbrella; they are, as such, excluded from practical and commercial opportunities in the EU. In this review, we will review the advances that are being made in the area of gene editing in microalgae and the impact of regulation on commercial advances in this area with consideration to the current regulatory framework as it relates to GMOs including GM microalgae in Europe.

  17. Health innovation for patient safety improvement.

    PubMed

    Sellappans, Renukha; Chua, Siew Siang; Tajuddin, Nur Amani Ahmad; Mei Lai, Pauline Siew

    2013-01-01

    Medication error has been identified as a major factor affecting patient safety. Many innovative efforts such as Computerised Physician Order Entry (CPOE), a Pharmacy Information System, automated dispensing machines and Point of Administration Systems have been carried out with the aim of improving medication safety. However, areas remain that require urgent attention. One main area will be the lack of continuity of care due to the breakdown of communication between multiple healthcare providers. Solutions may include consideration of "health smart cards" that carry vital patient medical information in the form of a "credit card" or use of the Malaysian identification card. However, costs and technical aspects associated with the implementation of this health smart card will be a significant barrier. Security and confidentiality, on the other hand, are expected to be of primary concern to patients. Challenges associated with the implementation of a health smart card might include physician buy-in for use in his or her everyday practice. Training and technical support should also be available to ensure the smooth implementation of this system. Despite these challenges, implementation of a health smart card moves us closer to seamless care in our country, thereby increasing the productivity and quality of healthcare.

  18. Current Challenges in the First Principle Quantitative Modelling of the Lower Hybrid Current Drive in Tokamaks

    NASA Astrophysics Data System (ADS)

    Peysson, Y.; Bonoli, P. T.; Chen, J.; Garofalo, A.; Hillairet, J.; Li, M.; Qian, J.; Shiraiwa, S.; Decker, J.; Ding, B. J.; Ekedahl, A.; Goniche, M.; Zhai, X.

    2017-10-01

    The Lower Hybrid (LH) wave is widely used in existing tokamaks for tailoring current density profile or extending pulse duration to steady-state regimes. Its high efficiency makes it particularly attractive for a fusion reactor, leading to consider it for this purpose in ITER tokamak. Nevertheless, if basics of the LH wave in tokamak plasma are well known, quantitative modeling of experimental observations based on first principles remains a highly challenging exercise, despite considerable numerical efforts achieved so far. In this context, a rigorous methodology must be carried out in the simulations to identify the minimum number of physical mechanisms that must be considered to reproduce experimental shot to shot observations and also scalings (density, power spectrum). Based on recent simulations carried out for EAST, Alcator C-Mod and Tore Supra tokamaks, the state of the art in LH modeling is reviewed. The capability of fast electron bremsstrahlung, internal inductance li and LH driven current at zero loop voltage to constrain all together LH simulations is discussed, as well as the needs of further improvements (diagnostics, codes, LH model), for robust interpretative and predictive simulations.

  19. Synthesis of 2D Metal Chalcogenide Thin Films through the Process Involving Solution-Phase Deposition.

    PubMed

    Giri, Anupam; Park, Gyeongbae; Yang, Heeseung; Pal, Monalisa; Kwak, Junghyeok; Jeong, Unyong

    2018-04-24

    2D metal chalcogenide thin films have recently attracted considerable attention owing to their unique physicochemical properties and great potential in a variety of applications. Synthesis of large-area 2D metal chalcogenide thin films in controllable ways remains a key challenge in this research field. Recently, the solution-based synthesis of 2D metal chalcogenide thin films has emerged as an alternative approach to vacuum-based synthesis because it is relatively simple and easy to scale up for high-throughput production. In addition, solution-based thin films open new opportunities that cannot be achieved from vacuum-based thin films. Here, a comprehensive summary regarding the basic structures and properties of different types of 2D metal chalcogenides, the mechanistic details of the chemical reactions in the synthesis of the metal chalcogenide thin films, recent successes in the synthesis by different reaction approaches, and the applications and potential uses is provided. In the last perspective section, the technical challenges to be overcome and the future research directions in the solution-based synthesis of 2D metal chalcogenides are discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Adaptive trials for tuberculosis: early reflections on theory and practice.

    PubMed

    Montgomery, C M

    2016-08-01

    Adaptive designs (ADs) have been proposed for anti-tuberculosis treatment trials. This call for innovation occurs against the backdrop of fundamental changes in the acceptable evidence base in anti-tuberculosis treatment. To contextualise ADs for tuberculosis (TB) and explore early responses from those working in the field. In this qualitative study investigating processes of theoretical and practical change in randomised controlled trials, 24 interviews were conducted with professionals involved in AD trials, half of whom worked in the TB field. Clinical trialists working on AD trials in TB are positive about the efficiency these designs offer, but remain cautious about their suitability. In addition to technical concerns, informants discussed the challenges of implementing AD in developing countries, including limited regulatory capacity to evaluate proposals, investments needed in infrastructure and site capacity, and challenges regarding informed consent. Respondents identified funding, interdisciplinary communication and regulatory and policy responses as additional concerns potentially affecting the success of AD for TB. Empirical research is needed into patient experiences of AD, including informed consent. Further consideration of the contexts of innovation in trial design is needed. These are fundamental to the successful translation of theory into practice.

  1. Control of the exercise hyperpnoea in humans: a modeling perspective.

    PubMed

    Ward, S A

    2000-09-01

    Models of the exercise hyperpnoea have classically incorporated elements of proportional feedback (carotid and medullary chemosensory) and feedforward (central and/or peripheral neurogenic) control. However, the precise details of the control process remain unresolved, reflecting in part both technical and interpretational limitations inherent in isolating putative control mechanisms in the intact human, and also the challenges to linear control theory presented by multiple-input integration, especially with regard to the ventilatory and gas-exchange complexities encountered at work rates which engender a metabolic acidosis. While some combination of neurogenic, chemoreflex and circulatory-coupled processes are likely to contribute to the control, the system appears to evidence considerable redundancy. This, coupled with the lack of appreciable error signals in the mean levels of arterial blood gas tensions and pH over a wide range of work rates, has motivated the formulation of innovative control models that reflect not only spatial interactions but also temporal interactions (i.e. memory). The challenge is to discriminate between robust competing control models that: (a) integrate such processes within plausible physiological equivalents; and (b) account for both the dynamic and steady-state system response over a range of exercise intensities. Such models are not yet available.

  2. Ethical Design of Intelligent Assistive Technologies for Dementia: A Descriptive Review.

    PubMed

    Ienca, Marcello; Wangmo, Tenzin; Jotterand, Fabrice; Kressig, Reto W; Elger, Bernice

    2017-09-22

    The use of Intelligent Assistive Technology (IAT) in dementia care opens the prospects of reducing the global burden of dementia and enabling novel opportunities to improve the lives of dementia patients. However, with current adoption rates being reportedly low, the potential of IATs might remain under-expressed as long as the reasons for suboptimal adoption remain unaddressed. Among these, ethical and social considerations are critical. This article reviews the spectrum of IATs for dementia and investigates the prevalence of ethical considerations in the design of current IATs. Our screening shows that a significant portion of current IATs is designed in the absence of explicit ethical considerations. These results suggest that the lack of ethical consideration might be a codeterminant of current structural limitations in the translation of IATs from designing labs to bedside. Based on these data, we call for a coordinated effort to proactively incorporate ethical considerations early in the design and development of new products.

  3. Physics and technological aspects of nanofluidics.

    PubMed

    Bocquet, Lyderic; Tabeling, Patrick

    2014-09-07

    From a physical perspective, nanofluidics represents an extremely rich domain. It hosts many mechanisms acting on the nanoscale, which combine together or interact with the confinement to generate new phenomena. Superfast flows in carbon nanotubes, nonlinear electrokinetic transport, slippage over smooth surfaces, nanobubble stability, etc. are the most striking phenomena that have been unveiled over the past few years, and some of them are still awaiting an explanation. One may anticipate that new nanofluidic effects will be discovered in the future, but at the moment, the technological barrier is high. Fabrication of nanochannels is most often a tour de force, slow and costly. However, with the accumulation of technological skills along with the use of new nanofluidic materials (like nanotubes), nanofluidics is becoming increasingly accessible to experimentalists. Among the technological challenges faced by the field, fabricating devices mimicking natural nanometric systems, such as aquaporins, ionic pumps or kidney osmotic filtering, seems the most demanding in terms of groundbreaking ideas. Nanoflow characterization remains delicate, although considerable progress has been achieved over the past years. The targeted application of nanofluidics is not only in the field of genomics and membrane science--with disruptive developments to be expected for water purification, desalination, and energy harvesting--but also for oil and gas production from unconventional reservoirs. Today, in view of the markets that are targeted, nanofluidics may well impact the industry more than microfluidics; this would represent an unexpected paradox. These successes rely on using a variety of materials and technologies, using state-of-the-art nanofabrication, or low-tech inexpensive approaches. As a whole, nanofluidics is a fascinating field that is facing considerable challenges today. It possesses a formidable potential and offers much space for creative groundbreaking ideas.

  4. Cloud ice: A climate model challenge with signs and expectations of progress

    NASA Astrophysics Data System (ADS)

    Waliser, Duane E.; Li, Jui-Lin F.; Woods, Christopher P.; Austin, Richard T.; Bacmeister, Julio; Chern, Jiundar; Del Genio, Anthony; Jiang, Jonathan H.; Kuang, Zhiming; Meng, Huan; Minnis, Patrick; Platnick, Steve; Rossow, William B.; Stephens, Graeme L.; Sun-Mack, Szedung; Tao, Wei-Kuo; Tompkins, Adrian M.; Vane, Deborah G.; Walker, Christopher; Wu, Dong

    2009-04-01

    Present-day shortcomings in the representation of upper tropospheric ice clouds in general circulation models (GCMs) lead to errors in weather and climate forecasts as well as account for a source of uncertainty in climate change projections. An ongoing challenge in rectifying these shortcomings has been the availability of adequate, high-quality, global observations targeting ice clouds and related precipitating hydrometeors. In addition, the inadequacy of the modeled physics and the often disjointed nature between model representation and the characteristics of the retrieved/observed values have hampered GCM development and validation efforts from making effective use of the measurements that have been available. Thus, even though parameterizations in GCMs accounting for cloud ice processes have, in some cases, become more sophisticated in recent years, this development has largely occurred independently of the global-scale measurements. With the relatively recent addition of satellite-derived products from Aura/Microwave Limb Sounder (MLS) and CloudSat, there are now considerably more resources with new and unique capabilities to evaluate GCMs. In this article, we illustrate the shortcomings evident in model representations of cloud ice through a comparison of the simulations assessed in the Intergovernmental Panel on Climate Change Fourth Assessment Report, briefly discuss the range of global observational resources that are available, and describe the essential components of the model parameterizations that characterize their "cloud" ice and related fields. Using this information as background, we (1) discuss some of the main considerations and cautions that must be taken into account in making model-data comparisons related to cloud ice, (2) illustrate present progress and uncertainties in applying satellite cloud ice (namely from MLS and CloudSat) to model diagnosis, (3) show some indications of model improvements, and finally (4) discuss a number of remaining questions and suggestions for pathways forward.

  5. Rethinking autonomy: decision making between patient and surgeon in advanced illnesses

    PubMed Central

    Hinshaw, Daniel B.

    2016-01-01

    Patients with advanced illness such as advanced stage cancer presenting with the need for possible surgical intervention can be some of the most challenging cases for a surgeon. Often there are multiple factors influencing the decisions made. For patients they are facing not just the effects of the disease on their body, but the stark realization that the disease will also limit their life. Not only are these factors a consideration when patients are making decisions, but also the desire to make the decision that is best for themselves, the autonomous decision. Also included in this process for the patient facing the possible need for an intervention is the surgeon. While patient autonomy remains one of the main principles within medicine, guiding treatment decisions, there is also the surgeon’s autonomy to be considered. Surgeons determine if there is even a possible intervention to be offered to patients, a decision making process that respects surgeons’ autonomous choices and includes elements of paternalism as surgeons utilize their expertise to make decisions. Included in the treatment decisions that are made and the care of the patient is the impact patients’ outcomes have on the surgeon, the inherent drive to be the best for the patient and desire for good outcomes for the patient. While both the patient’s and surgeon’s autonomy are a dynamic interface influencing decision making, the main goal for the patient facing a palliative procedure is that of making treatment decisions based on the concept of shared decision making, always giving primary consideration to the patient’s goals and values. Lastly, regardless of the decision made, it is the responsibility of surgeons to their patients to be a source of support through this challenging time. PMID:27004224

  6. Case Report: The Specter of Untreated Congenital Hypothyroidism in Immigrant Families

    PubMed Central

    Hamdoun, Elwaseila; Karachunski, Peter; Nathan, Brandon; Fischer, Melissa; Torkelson, Jane L.; Drilling, Amy

    2016-01-01

    Newborn screening has dramatically reduced rates of untreated congenital hypothyroidism (CH). However, in low-income nations where newborn screening programs do not exist, untreated CH remains a significant health and societal challenge. The goal of this report is to alert health care providers about the potential of undiagnosed CH in unscreened immigrant children. We report 3 siblings of Somali descent with CH who started treatment with levothyroxine at age 0.5 years, 7.7 years, and 14.8 years and were followed for 8 years. This case series demonstrates a spectrum of severity, response to treatment, and neurocognitive and growth outcomes depending on the age at treatment initiation. Patient 1, now 22 years old, went undiagnosed for 14.8 years. On diagnosis, his height was –7.5 SDs with a very delayed bone age of –13.5 SDs. His longstanding CH was associated with empty sella syndrome, static encephalopathy, and severe musculoskeletal deformities. Even after treatment, his height (–5.2 SDs) and cognitive deficits remained the most severe of the 3 siblings. Patient 2, diagnosed at 7.7 years, had moderate CH manifestations and thus a relatively intermediate outcome after treatment. Patient 3, who had the earliest diagnosis at 0.5 years, displayed the best response, but continues to have residual global developmental delay. In conclusion, untreated CH remains an important diagnostic consideration among immigrant children. PMID:27244801

  7. Case Report: The Specter of Untreated Congenital Hypothyroidism in Immigrant Families.

    PubMed

    Hamdoun, Elwaseila; Karachunski, Peter; Nathan, Brandon; Fischer, Melissa; Torkelson, Jane L; Drilling, Amy; Petryk, Anna

    2016-05-01

    Newborn screening has dramatically reduced rates of untreated congenital hypothyroidism (CH). However, in low-income nations where newborn screening programs do not exist, untreated CH remains a significant health and societal challenge. The goal of this report is to alert health care providers about the potential of undiagnosed CH in unscreened immigrant children. We report 3 siblings of Somali descent with CH who started treatment with levothyroxine at age 0.5 years, 7.7 years, and 14.8 years and were followed for 8 years. This case series demonstrates a spectrum of severity, response to treatment, and neurocognitive and growth outcomes depending on the age at treatment initiation. Patient 1, now 22 years old, went undiagnosed for 14.8 years. On diagnosis, his height was -7.5 SDs with a very delayed bone age of -13.5 SDs. His longstanding CH was associated with empty sella syndrome, static encephalopathy, and severe musculoskeletal deformities. Even after treatment, his height (-5.2 SDs) and cognitive deficits remained the most severe of the 3 siblings. Patient 2, diagnosed at 7.7 years, had moderate CH manifestations and thus a relatively intermediate outcome after treatment. Patient 3, who had the earliest diagnosis at 0.5 years, displayed the best response, but continues to have residual global developmental delay. In conclusion, untreated CH remains an important diagnostic consideration among immigrant children. Copyright © 2016 by the American Academy of Pediatrics.

  8. Trends in health surveillance and joint service delivery for pastoralists in West and Central Africa.

    PubMed

    Abakar, M F; Schelling, E; Béchir, M; Ngandolo, B N; Pfister, K; Alfaroukh, I O; Hassane, H M; Zinsstag, J

    2016-11-01

    In most sub-Saharan African countries, pastoralism represents an important economic resource and contributes significantly to national growth; however, challenges remain, particularly in providing social services to pastoralists (especially health and education) and in avoiding conflict with local sedentary communities and local authorities. All of this takes place while pastoralists try to maintain their mobile lifestyle within a rapidly changing ecosystem. Transdisciplinary approaches, such as 'One Health', which covers both human and animal health, have proven effective in delivering services and reaching mobile pastoralists in remote areas. The pastoralist way of life could be described as being linked to both their livestock and their environment, which makes social science an important element when researching the delivery and adaptation of social services to pastoralists. Early or pre-diagnostic detection of emerging and endemic infectious disease remains a vital aspect of health surveillance targeted at preventing further transmission and spread. Community-based syndromic surveillance, coupled with visual mobile phone technology, adapted to the high levels of illiteracy among nomads, could offer an alternative to existing health surveillance systems. Such an approach could contribute to accelerated reporting, which could in turn lead to targeted intervention among mobile pastoralists in sub-Saharan Africa. Although considerable efforts have been made towards integrating mobile pastoralists into social services, obstacles remain to the adoption of a clear, specific and sustainable policy on pastoralism in sub-Saharan Africa.

  9. High Levels of Dual-Class Drug Resistance in HIV-Infected Children Failing First-Line Antiretroviral Therapy in Southern Ethiopia

    PubMed Central

    Kinloch, Natalie N.; Lapointe, Hope R.; Cobarrubias, Kyle D.; Foster, Byron A.; Jerene, Degu; Makonnen, Eyasu; Brumme, Zabrina L.

    2018-01-01

    Clinical monitoring of pediatric HIV treatment remains a major challenge in settings where drug resistance genotyping is not routinely available. As a result, our understanding of drug resistance, and its impact on subsequent therapeutic regimens available in these settings, remains limited. We investigate the prevalence and correlates of HIV-1 drug resistance among 94 participants of the Ethiopia Pediatric HIV Cohort failing first-line combination antiretroviral therapy (cART) using dried blood spot-based genotyping. Overall, 81% (73/90) of successfully genotyped participants harbored resistance mutations, including 69% (62/90) who harbored resistance to both Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs). Strikingly, 42% of resistant participants harbored resistance to all four NRTIs recommended for second-line use in this setting, meaning that there are effectively no remaining cART options for these children. Longer cART duration and prior regimen changes were significantly associated with detection of drug resistance mutations. Replicate genotyping increased the breadth of drug resistance detected in 34% of cases, and thus is recommended for consideration when typing from blood spots. Implementation of timely drug resistance testing and access to newer antiretrovirals and drug classes are urgently needed to guide clinical decision-making and improve outcomes for HIV-infected children on first-line cART in Ethiopia. PMID:29389912

  10. Challenges to the Development and Implementation of Public Policies to Achieve Animal Welfare Outcomes.

    PubMed

    Rose, Margaret

    2010-12-31

    Although there is a long-established tradition of concern for the welfare of animals, it was not until the mid 1800's that governments sought to enact legislation to protect animals from cruelty. In the 1950's, questions concerning animal welfare re-emerged and in the ensuing years have been an on-going focus of government activities. These developments occurred against a backdrop of significant social change but there are important differences in what now underpins and informs these considerations. In the formulation and implementation of public policies, governments look for a course of action that represents and protects the interests of the community; the process may be challenging with competing interests but the final determination seeks a middle ground that best meets the needs and interests of the community as a whole. When policy development concerns our relationship with other animals, the complexity of this relationship presents particular challenges not only to the formulation of policies but also to the evaluation of outcomes. Notably, the depth of feelings and diversity of views in our community reflect the complex social, cultural and personal dimensions of this relationship. The use of animals for scientific purposes remains one of the most contentious animal welfare issues primarily because when animals are used for these purposes, accepted animal welfare benchmarks cannot always be met. Based on the Australian experience, this paper will discuss the influences in and on-going challenges to the development and implementation of public policy when animals are used for these purposes.

  11. Workflows and performances in the ranking prediction of 2016 D3R Grand Challenge 2: lessons learned from a collaborative effort.

    PubMed

    Gao, Ying-Duo; Hu, Yuan; Crespo, Alejandro; Wang, Deping; Armacost, Kira A; Fells, James I; Fradera, Xavier; Wang, Hongwu; Wang, Huijun; Sherborne, Brad; Verras, Andreas; Peng, Zhengwei

    2018-01-01

    The 2016 D3R Grand Challenge 2 includes both pose and affinity or ranking predictions. This article is focused exclusively on affinity predictions submitted to the D3R challenge from a collaborative effort of the modeling and informatics group. Our submissions include ranking of 102 ligands covering 4 different chemotypes against the FXR ligand binding domain structure, and the relative binding affinity predictions of the two designated free energy subsets of 15 and 18 compounds. Using all the complex structures prepared in the same way allowed us to cover many types of workflows and compare their performances effectively. We evaluated typical workflows used in our daily structure-based design modeling support, which include docking scores, force field-based scores, QM/MM, MMGBSA, MD-MMGBSA, and MacroModel interaction energy estimations. The best performing methods for the two free energy subsets are discussed. Our results suggest that affinity ranking still remains very challenging; that the knowledge of more structural information does not necessarily yield more accurate predictions; and that visual inspection and human intervention are considerably important for ranking. Knowledge of the mode of action and protein flexibility along with visualization tools that depict polar and hydrophobic maps are very useful for visual inspection. QM/MM-based workflows were found to be powerful in affinity ranking and are encouraged to be applied more often. The standardized input and output enable systematic analysis and support methodology development and improvement for high level blinded predictions.

  12. Workflows and performances in the ranking prediction of 2016 D3R Grand Challenge 2: lessons learned from a collaborative effort

    NASA Astrophysics Data System (ADS)

    Gao, Ying-Duo; Hu, Yuan; Crespo, Alejandro; Wang, Deping; Armacost, Kira A.; Fells, James I.; Fradera, Xavier; Wang, Hongwu; Wang, Huijun; Sherborne, Brad; Verras, Andreas; Peng, Zhengwei

    2018-01-01

    The 2016 D3R Grand Challenge 2 includes both pose and affinity or ranking predictions. This article is focused exclusively on affinity predictions submitted to the D3R challenge from a collaborative effort of the modeling and informatics group. Our submissions include ranking of 102 ligands covering 4 different chemotypes against the FXR ligand binding domain structure, and the relative binding affinity predictions of the two designated free energy subsets of 15 and 18 compounds. Using all the complex structures prepared in the same way allowed us to cover many types of workflows and compare their performances effectively. We evaluated typical workflows used in our daily structure-based design modeling support, which include docking scores, force field-based scores, QM/MM, MMGBSA, MD-MMGBSA, and MacroModel interaction energy estimations. The best performing methods for the two free energy subsets are discussed. Our results suggest that affinity ranking still remains very challenging; that the knowledge of more structural information does not necessarily yield more accurate predictions; and that visual inspection and human intervention are considerably important for ranking. Knowledge of the mode of action and protein flexibility along with visualization tools that depict polar and hydrophobic maps are very useful for visual inspection. QM/MM-based workflows were found to be powerful in affinity ranking and are encouraged to be applied more often. The standardized input and output enable systematic analysis and support methodology development and improvement for high level blinded predictions.

  13. Challenges and Opportunities for Testing Students Who Are Deaf or Hard of Hearing: Information for Educators on Creating Test Equity. Test Equity Considerations: Schools

    ERIC Educational Resources Information Center

    PEPNet-West, 2010

    2010-01-01

    For most students, test taking is a challenge. For students who are deaf or hard of hearing, classroom quizzes, tests, and exams are even more challenging. Standardized tests--The SAT, ACT, state proficiency tests, No Child Left Behind annual tests, and psychoeducational evaluations--present additional challenges for students who are deaf or hard…

  14. Determining the Ecosystem Services Important for Urban Landscapes

    EPA Science Inventory

    Urban ecosystems present special considerations and challenges in researching and evaluating ecosystem functions and services. A case study of nitrate retention and loss in forested, urban wetlands illustrates these challenges. Water table dynamics, in situ nitrogen cy...

  15. From Two-Phase to Three-Phase: The New Electrochemical Interface by Oxide Electrocatalysts

    NASA Astrophysics Data System (ADS)

    Xu, Zhichuan J.

    2018-03-01

    Electrochemical reactions typically occur at the interface between a solid electrode and a liquid electrolyte. The charge exchange behaviour between these two phases determines the kinetics of electrochemical reactions. In the past few years, significant advances have been made in the development of metal oxide electrocatalysts for fuel cell and electrolyser reactions. However, considerable gaps remain in the fundamental understanding of the charge transfer pathways and the interaction between the metal oxides and the conducting substrate on which they are located. In particular, the electrochemical interfaces of metal oxides are significantly different from the traditional (metal) ones, where only a conductive solid electrode and a liquid electrolyte are considered. Oxides are insulating and have to be combined with carbon as a conductive mediator. This electrode configuration results in a three-phase electrochemical interface, consisting of the insulating oxide, the conductive carbon, and the liquid electrolyte. To date, the mechanistic insights into this kind of non-traditional electrochemical interface remain unclear. Consequently conventional electrochemistry concepts, established on classical electrode materials and their two-phase interfaces, are facing challenges when employed for explaining these new electrode materials. [Figure not available: see fulltext.

  16. Tetragonal bismuth bilayer: A stable and robust quantum spin hall insulator

    DOE PAGES

    Kou, Liangzhi; Tan, Xin; Ma, Yandong; ...

    2015-11-23

    In this study, topological insulators (TIs) exhibit novel physics with great promise for new devices, but considerable challenges remain to identify TIs with high structural stability and large nontrivial band gap suitable for practical applications. Here we predict by first-principles calculations a two-dimensional (2D) TI, also known as a quantum spin Hall (QSH) insulator, in a tetragonal bismuth bilayer (TB-Bi) structure that is dynamically and thermally stable based on phonon calculations and finite-temperature molecular dynamics simulations. Density functional theory and tight-binding calculations reveal a band inversion among the Bi-p orbits driven by the strong intrinsic spin–orbit coupling, producing a largemore » nontrivial band gap, which can be effectively tuned by moderate strains. The helical gapless edge states exhibit a linear dispersion with a high Fermi velocity comparable to that of graphene, and the QSH phase remains robust on a NaCl substrate. These remarkable properties place TB-Bi among the most promising 2D TIs for high-speed spintronic devices, and the present results provide insights into the intriguing QSH phenomenon in this new Bi structure and offer guidance for its implementation in potential applications.« less

  17. Antiviral agents and HIV prevention: controversies, conflicts, and consensus

    PubMed Central

    Cohen, Myron S.; Muessig, Kathryn E.; Smith, M. Kumi; Powers, Kimberly A.; Kashuba, Angela D.M.

    2013-01-01

    Antiviral agents can be used to prevent HIV transmission before exposure as preexpo-sure prophylaxis (PrEP), after exposure as postexposure prophylaxis, and as treatment of infected people for secondary prevention. Considerable research has shed new light on antiviral agents for PrEP and for prevention of secondary HIV transmission. While promising results have emerged from several PrEP trials, the challenges of poor adherence among HIV-negative clients and possible increase in sexual risk behaviors remain a concern. In addition, a broader pipeline of antiviral agents for PrEP that focuses on genital tract pharmacology and safety and resistance issues must be developed. Antiretroviral drugs have also been used to prevent HIV transmission from HIV-infected patients to their HIV-discordant sexual partners. The HIV Prevention Trials Network 052 trial demonstrated nearly complete prevention of HIV transmission by early treatment of infection, but the generalizability of the results to other risk groups – including intravenous drug users and MSM – has not been determined. Most importantly, the best strategy for use of antiretroviral agents to reduce the spread of HIV at either the individual level or the population level has not been developed, and remains the ultimate goal of this area of investigation. PMID:22507927

  18. Convection-enhanced delivery for the treatment of glioblastoma

    PubMed Central

    Vogelbaum, Michael A.; Aghi, Manish K.

    2015-01-01

    Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low–positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique. PMID:25746090

  19. The state of Health in All policies (HiAP) in the European Union: potential and pitfalls.

    PubMed

    Koivusalo, Meri

    2010-06-01

    Health in All Policies (HiAP) was formally legitimated as a European Union (EU) approach in 2006. It resulted from more long-term efforts to enhance action on considering health and health policy implications of other policies, as well as recognition that European-level policies affect health systems and scope for health-related regulation at national level. However, implementation of HiAP has remained a challenge. European-level efforts to use health impact assessment to benefit public health and health systems have not become strengthened by the new procedures. And, as a result of the Lisbon Treaty, European-level policy-making is expected to become more important in shaping national policies. HiAP has at European level remained mostly as rhetoric, but legitimate health arguments and provides policy space for health articulation within EU policy-making. HiAP is a broader approach than health impact assessment and at European level requires consideration of mechanisms that recognise the nature of European policy-making, as well as extending from administrative tools to increased transparency, accountability and scope for health and health policy-related arguments within political decision-making in the EU.

  20. Burn injury: review of pathophysiology and therapeutic modalities in major burns.

    PubMed

    Kaddoura, I; Abu-Sittah, G; Ibrahim, A; Karamanoukian, R; Papazian, N

    2017-06-30

    Despite a considerable decrease in their incidence worldwide, burn injuries remain one of the commonest forms of trauma and account for a weighty proportion of trauma cases in health-care emergencies around the globe. Although the latest data reveal a substantial decline in burn-related mortality and hospital admissions in the US over the past three decades, severe thermal injuries continue to trigger devastating morbidity and significant mortality while their management remains a dynamic challenge for the entire medical and paramedical community. Concrete evidence continues to be established regarding burn-associated pathophysiologic responses, and their destructive sequelae and deleterious effects in survivors at cellular, systemic as well as socio-economic level. Better understanding of these responses have contributed to advances in therapeutic strategies, improved long-term outcomes and catalyzed the reintegration of victims back into society. This paper describes the current understanding of the pathophysiology of a burn injury and characterizes both local and systemic pathophysiologic responses in terms of metabolic, hemodynamics, cardiac, renal, hepatic, gastro-intestinal, immunologic, endocrine as well as male reproductive systems in an attempt to understand the corresponding treatment modalities for this unique patient population.

  1. Burn injury: review of pathophysiology and therapeutic modalities in major burns

    PubMed Central

    Kaddoura, I.; Abu-Sittah, G.; Ibrahim, A.; Karamanoukian, R.; Papazian, N.

    2017-01-01

    Summary Despite a considerable decrease in their incidence worldwide, burn injuries remain one of the commonest forms of trauma and account for a weighty proportion of trauma cases in health-care emergencies around the globe. Although the latest data reveal a substantial decline in burn-related mortality and hospital admissions in the US over the past three decades, severe thermal injuries continue to trigger devastating morbidity and significant mortality while their management remains a dynamic challenge for the entire medical and paramedical community. Concrete evidence continues to be established regarding burn-associated pathophysiologic responses, and their destructive sequelae and deleterious effects in survivors at cellular, systemic as well as socio-economic level. Better understanding of these responses have contributed to advances in therapeutic strategies, improved long-term outcomes and catalyzed the reintegration of victims back into society. This paper describes the current understanding of the pathophysiology of a burn injury and characterizes both local and systemic pathophysiologic responses in terms of metabolic, hemodynamics, cardiac, renal, hepatic, gastro-intestinal, immunologic, endocrine as well as male reproductive systems in an attempt to understand the corresponding treatment modalities for this unique patient population. PMID:29021720

  2. Health Surveys Using Mobile Phones in Developing Countries: Automated Active Strata Monitoring and Other Statistical Considerations for Improving Precision and Reducing Biases

    PubMed Central

    Blynn, Emily; Ahmed, Saifuddin; Gibson, Dustin; Pariyo, George; Hyder, Adnan A

    2017-01-01

    In low- and middle-income countries (LMICs), historically, household surveys have been carried out by face-to-face interviews to collect survey data related to risk factors for noncommunicable diseases. The proliferation of mobile phone ownership and the access it provides in these countries offers a new opportunity to remotely conduct surveys with increased efficiency and reduced cost. However, the near-ubiquitous ownership of phones, high population mobility, and low cost require a re-examination of statistical recommendations for mobile phone surveys (MPS), especially when surveys are automated. As with landline surveys, random digit dialing remains the most appropriate approach to develop an ideal survey-sampling frame. Once the survey is complete, poststratification weights are generally applied to reduce estimate bias and to adjust for selectivity due to mobile ownership. Since weights increase design effects and reduce sampling efficiency, we introduce the concept of automated active strata monitoring to improve representativeness of the sample distribution to that of the source population. Although some statistical challenges remain, MPS represent a promising emerging means for population-level data collection in LMICs. PMID:28476726

  3. Transsphenoidal surgery in patients with acromegaly: operative strategies for overcoming technically challenging anatomical variations.

    PubMed

    Zada, Gabriel; Cavallo, Luigi M; Esposito, Felice; Fernandez-Jimenez, Julio Cesar; Tasiou, Anastasia; De Angelis, Michelangelo; Cafiero, Tullio; Cappabianca, Paolo; Laws, Edward R

    2010-10-01

    In addition to difficulties with anesthetic and medical management, transsphenoidal operations in patients with longstanding acromegaly are associated with inherent intraoperative challenges because of anatomical variations that occur frequently in these patients. The object of this study was to review the overall safety profile and anatomical/technical challenges associated with transsphenoidal surgery in patients with acromegaly. The authors performed a retrospective analysis of 169 patients who underwent endoscopic transsphenoidal operations for growth hormone-secreting adenomas to assess the incidence of surgical complications. A review of frequently occurring anatomical challenges and operative strategies employed during each phase of the operation to address these particular issues was performed. Of 169 cases reviewed, there was no perioperative mortality. Internal carotid artery injury occurred in 1 patient (0.6%) with complex sinus anatomy, who remained neurologically intact following endovascular unilateral carotid artery occlusion. Other complications included: significant postoperative epistaxis (5 patients [3%]), transient diabetes insipidus (5 patients [3%]), delayed symptomatic hyponatremia (4 patients [2%]), CSF leak (2 patients [1%]), and pancreatitis (1 patient [0.6%]). Preoperative considerations in patients with acromegaly should include a cardiopulmonary evaluation and planning regarding intubation and other aspects of the anesthetic technique. During the nasal phase of the transsphenoidal operation, primary challenges include maintaining adequate visualization and hemostasis, which is frequently compromised by redundant, edematous nasal mucosa and bony hypertrophy of the septum and the nasal turbinates. During the sphenoid phase, adequate bony removal, optimization of working space, and correlation of imaging studies to intraoperative anatomy are major priorities. The sellar phase is frequently challenged by increased sellar floor thickness, distinct patterns of tumor extension and bony invasion, and anatomical variations in the caliber and course of the internal carotid artery. Specific operative techniques for addressing each of these intraoperative challenges are discussed. Transsphenoidal surgery in patients with longstanding acromegaly frequently poses greater challenges than operations for other types of sellar lesions, yet these challenges may be safely and effectively overcome with the anticipation of specific issues and implementation of various intraoperative techniques.

  4. Practicalities and Research Considerations for Conducting Childhood Obesity Prevention Interventions with Families

    PubMed Central

    Morgan, Philip J.; Jones, Rachel A.; Collins, Clare E.; Hesketh, Kylie D.; Young, Myles D.; Burrows, Tracy L.; Magarey, Anthea M.; Brown, Helen L.; Hinkley, Trina; Perry, Rebecca A.; Brennan, Leah; Spence, Alison C.; Campbell, Karen J.

    2016-01-01

    Internationally, childhood obesity is a major public health concern. Given the established difficulties in treating obesity, designing and evaluating effective obesity prevention interventions are research priorities. As parents play a crucial role in establishing positive health behaviours in children, they are a key target for child obesity prevention programs. However, recruiting and engaging parents in such interventions can be a considerable challenge for researchers and practitioners. Members of the ‘Parenting, Child Behaviour and Well-being’ stream of the Australasian Child and Adolescent Obesity Research Network (ACAORN) have considerable and varied expertise in conducting such interventions and can provide insights into addressing these challenges. This paper aims to highlight considerations regarding the design, implementation, and evaluation of obesity prevention interventions with families and provide practical insights and recommendations for researchers and practitioners conducting family-based research in this area. Case studies of three family-based interventions conducted by ACAORN members are highlighted to provide examples and contextualise the recommendations proposed. PMID:27834820

  5. Model and experiments to optimize co-adaptation in a simplified myoelectric control system.

    PubMed

    Couraud, M; Cattaert, D; Paclet, F; Oudeyer, P Y; de Rugy, A

    2018-04-01

    To compensate for a limb lost in an amputation, myoelectric prostheses use surface electromyography (EMG) from the remaining muscles to control the prosthesis. Despite considerable progress, myoelectric controls remain markedly different from the way we normally control movements, and require intense user adaptation. To overcome this, our goal is to explore concurrent machine co-adaptation techniques that are developed in the field of brain-machine interface, and that are beginning to be used in myoelectric controls. We combined a simplified myoelectric control with a perturbation for which human adaptation is well characterized and modeled, in order to explore co-adaptation settings in a principled manner. First, we reproduced results obtained in a classical visuomotor rotation paradigm in our simplified myoelectric context, where we rotate the muscle pulling vectors used to reconstruct wrist force from EMG. Then, a model of human adaptation in response to directional error was used to simulate various co-adaptation settings, where perturbations and machine co-adaptation are both applied on muscle pulling vectors. These simulations established that a relatively low gain of machine co-adaptation that minimizes final errors generates slow and incomplete adaptation, while higher gains increase adaptation rate but also errors by amplifying noise. After experimental verification on real subjects, we tested a variable gain that cumulates the advantages of both, and implemented it with directionally tuned neurons similar to those used to model human adaptation. This enables machine co-adaptation to locally improve myoelectric control, and to absorb more challenging perturbations. The simplified context used here enabled to explore co-adaptation settings in both simulations and experiments, and to raise important considerations such as the need for a variable gain encoded locally. The benefits and limits of extending this approach to more complex and functional myoelectric contexts are discussed.

  6. [Tularaemia - a forgotten disease? Own experience].

    PubMed

    Yanushevych, Mariya; Komorowska-Piotrowska, Anna; Feleszko, Wojciech

    2013-01-01

    Tularaemia is an acute, animal-born disease, caused by Gram-negative aerobic bacilli - Francisella tularensis. Due to its high infectiousness and virulence it remains an epidemiological issue in some countries. The prevalence rate of tularaemia in the Scandinavian region, where most of the cases among European countries have been reported, it has remained stable since 2006, whereas in Poland a small, but stable increase has been observed. The first case of tularaemia in Poland was diagnosed in 1949 and since then more than 600 cases have been reported, mainly in the north-eastern and north-western regions of the country. In the majority of cases the infection has been transmitted by ixode bites or through direct contact with infected animals. Depending on the route of transmission, tularaemia can develop in different forms with a characteristic sudden onset of high fever and local lymphadenopathy. In Europe 95% of cases account for the ulceroglandular type, which characteristically presents with skin ulceration and inflammation of regional tissues and lymph nodes. This is the reason why it should always be taken into consideration in differential diagnosis of lymphadenitis, especially if its course is atypical or it does not respond to antibiotic therapy. The above mentioned atypical course of the disease and resistance to empirical treatment contribute to the challenge encountered by physicians in the process of diagnosis and treatment. The aim of the study is to present the most important data on tularaemia as an animal-born, infectious disease and to convince physicians to take it into consideration in the differential diagnosis of ymphadenopathy. We illustrate this article with the case of ulceroglandular type of tularemia diagnosed in a 5 year-old boy and describe the encountered diagnostic and therapeutic problems.

  7. Efficacy and tolerability of old and new drugs used in the treatment of immune thrombocytopenia: Results from a long-term observation in clinical practice

    PubMed Central

    Depré, Fabian; Aboud, Nasra; Mayer, Beate; Salama, Abdulgabar

    2018-01-01

    Background Many patients with immune thrombocytopenia (ITP) may require special attention and long-term treatment. Little is known on the efficacy and tolerability of the drugs used in practice. Material and methods We retrospectively reviewed the results of therapy of 400 patients with chronic ITP. All Patients were treated at our institution between 1996–2016 under consideration of guidelines, general recommendations, and individual aspects, including gender, age, weight, comorbidity, patient’s medical history and bleeding risk. Results Treatment was not required in 25% of patients (n = 100) during observation. In treated patients (n = 300), the rate of patients that responded and tolerated treatment with prednisolone was 59% (52/88), with azathioprine 32% (29/90), with eltrombopag 49% (31/63), with romiplostim 59% 27/45, with IVIG (intravenous immunoglobulines) 75% (94/126), with anti-D 37% (19/52) and with dexamethasone 60% (25/42) patients. Eighteen treated patients (6%) entered sustained remission after treatment with various drugs. Twenty-six patients underwent splenectomy (Splx) resulting in sustained remission in 15 cases (60%). Only two patients remained refractory to Splx and to all used drugs. Discussion None of the currently available drugs used in the treatment of ITP are invariably safe and effective. Responses, the duration of response, intolerability, and the course of disease are unpredictable. Although the treatment of ITP has considerably improved in the recent years, the currently available drugs may rarely cure affected patients. The need for safe and effective therapy in ITP is evident. Optimal treatment decisions for each patient remains a challenge in many cases. PMID:29856800

  8. Cultural Considerations in Counseling Couples Who Experience Infertility

    ERIC Educational Resources Information Center

    Burnett, Judith A.

    2009-01-01

    Infertility creates challenges affecting various aspects of couples' intimate lives. Practices regarding reproduction are often shaped by cultural messages. Culturally sensitive treatment methods help counselors provide effective therapy to couples with fertility problems. This article describes cultural influences, challenges, and counseling…

  9. Validation of sterilizing grade filtration.

    PubMed

    Jornitz, M W; Meltzer, T H

    2003-01-01

    Validation consideration of sterilizing grade filters, namely 0.2 micron, changed when FDA voiced concerns about the validity of Bacterial Challenge tests performed in the past. Such validation exercises are nowadays considered to be filter qualification. Filter validation requires more thorough analysis, especially Bacterial Challenge testing with the actual drug product under process conditions. To do so, viability testing is a necessity to determine the Bacterial Challenge test methodology. Additionally to these two compulsory tests, other evaluations like extractable, adsorption and chemical compatibility tests should be considered. PDA Technical Report # 26, Sterilizing Filtration of Liquids, describes all parameters and aspects required for the comprehensive validation of filters. The report is a most helpful tool for validation of liquid filters used in the biopharmaceutical industry. It sets the cornerstones of validation requirements and other filtration considerations.

  10. Pharmacogenomic Testing for Neuropsychiatric Drugs: Current Status of Drug Labeling, Guidelines for Using Genetic Information, and Test Options

    PubMed Central

    Drozda, Katarzyna; Müller, Daniel J.; Bishop, Jeffrey R.

    2014-01-01

    Advancements in pharmacogenomics have introduced an increasing number of opportunities to bring personalized medicine into clinical practice. Understanding how and when to use this technology to help guide pharmacotherapy used to treat neuropsychiatric conditions remains a challenge for many clinicians. Currently, guidelines exist to assist clinicians in the use of genetic information for drug selection and/or dosing for the tricyclic antidepressants, carbamazepine, and phenytoin. Additional language in the product labeling suggests that genetic information may also be useful for assessing the starting and target doses, as well as drug interaction potential, for a number of other medications used to treat psychiatric and neurological conditions. In this review, we outline the current status of pharmacogenomic testing for neuropsychiatric drugs as it pertains to information contained in drug labeling, consensus guidelines, and test panels, as well as considerations related to obtaining tests for patients. PMID:24523097

  11. Current limitations of the assessment of haemostasis in adult extracorporeal membrane oxygenation patients and the role of point-of-care testing.

    PubMed

    Venkatesh, K; Nair, P S; Hoechter, D J; Buscher, H

    2016-11-01

    Haemostatic perturbations are commonly seen in extracorporeal membrane oxygenation (ECMO) patients and remain a clinical challenge, contributing significantly to morbidity and mortality. The approach to anticoagulation monitoring and the management of bleeding varies considerably across ECMO centres. Routine laboratory tests have their limitations in terms of turnaround time and specificity of information provided. Newer point-of-care testing (POCT) for coagulation may overcome these issues, as it provides information about the entire coagulation pathway from clot initiation to lysis. It is also possible to obtain qualitative information on platelet function from these tests. Furthermore, the ability to incorporate these results into a goal-directed algorithm to manage bleeding with targeted transfusion strategies appears particularly attractive and cost effective. Further studies are required to evaluate the utility of POCT to optimise bleeding and anticoagulation management in these complex patients.

  12. Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering☆

    PubMed Central

    Moioli, Eduardo K.; Clark, Paul A.; Xin, Xuejun; Lal, Shan; Mao, Jeremy J.

    2010-01-01

    Current treatments for diseases and trauma of dental, oral and craniofacial (DOC) structures rely on durable materials such as amalgam and synthetic materials, or autologous tissue grafts. A paradigm shift has taken place to utilize tissue engineering and drug delivery approaches towards the regeneration of these structures. Several prototypes of DOC structures have been regenerated such as temporomandibular joint (TMJ) condyle, cranial sutures, tooth structures and periodontium components. However, many challenges remain when taking in consideration the high demand for esthetics of DOC structures, the complex environment and yet minimal scar formation in the oral cavity, and the need for accommodating multiple tissue phenotypes. This review highlights recent advances in the regeneration of DOC structures, including the tooth, periodontium, TMJ, cranial sutures and implant dentistry, with specific emphasis on controlled release of signaling cues for stem cells, biomaterial matrices and scaffolds, and integrated tissue engineering approaches. PMID:17499385

  13. A Critical Appraisal of Extracorporeal Photopheresis as a Treatment Modality for Acute and Chronic Graft-Versus-Host Disease

    PubMed Central

    Rafei, Hind; A. Kharfan-Dabaja, Mohamed

    2017-01-01

    Although significant advances have been made in the biologic understanding of graft-versus-host disease (GVHD) and its treatment options, GVHD remains the single most challenging obstacle to the success of allogeneic hematopoietic cell transplantation (HCT) due to high risk of disabling morbidity and mortality. Extracorporeal photopheresis (ECP) has promising effects in controlling steroid-refractory GVHD, both acute and chronic, and it has been studied extensively. Its putative immunomodulatory mechanisms, while not immunosuppressive, position ECP as an attractive treatment strategy for GVHD patients who are already receiving global immunosuppression. However, ECP is relatively underutilized due in part to limited access and time commitment. Here, we review the recent findings on the ECP efficacy in both acute and chronic GVHD, primarily for steroid-refractory status, and we critically appraise its benefits. We also explore salient considerations on the optimal use of ECP in the treatment of refractory GVHD. PMID:29019937

  14. [CARDIOVASCULAR INVOLVEMENTS IN BEHÇET'S DISEASE: "ANGIO-BEHÇET"].

    PubMed

    Tridetti, J; Benoit, A; Borgoens, P; Hoffer, E

    2016-01-01

    Behçet's disease is a relapsing, immune-mediated systemic vasculitis that may affect blood vessels of all types and sizes. Nowadays, the etiology remains unclear. In the absence of a biological marker or pathognomonic radiology, the diagnosis is mainly based on clinical manifestations. The cardiovascular involvement, known as "angio-Behçet", is relatively common and affects up to 40% of patients. It typi- cally occurs in a young male, usually during the onset of the disease. In general, immunosuppressive and anticoagulant therapies initiated early are likely to induce a remarkable cli- nical improvement. Nevertheless, prompt recognition of the polymorphous cardiovascular manifestations of the disease is challenging and may be responsible for some considerable delay prior to initiation of adequate therapy. The aim of this article is to describe the spectrum of cardiovascular involve- ments of Behçet's disease in order to optimize detection and therapeutic management.

  15. Sexy but often unreliable: the impact of unreliability on the replicability of experimental findings with implicit measures.

    PubMed

    Lebel, Etienne P; Paunonen, Sampo V

    2011-04-01

    Implicit measures have contributed to important insights in almost every area of psychology. However, various issues and challenges remain concerning their use, one of which is their considerable variation in reliability, with many implicit measures having questionable reliability. The goal of the present investigation was to examine an overlooked consequence of this liability with respect to replication, when such implicit measures are used as dependent variables in experimental studies. Using a Monte Carlo simulation, the authors demonstrate that a higher level of unreliability in such dependent variables is associated with substantially lower levels of replicability. The results imply that this overlooked consequence can have far-reaching repercussions for the development of a cumulative science. The authors recommend the routine assessment and reporting of the reliability of implicit measures and also urge the improvement of implicit measures with low reliability.

  16. Integrated Control Strategy of Schistosomiasis in The People's Republic of China: Projects Involving Agriculture, Water Conservancy, Forestry, Sanitation and Environmental Modification.

    PubMed

    Yang, Y; Zhou, Y-B; Song, X-X; Li, S-Z; Zhong, B; Wang, T-P; Bergquist, R; Zhou, X-N; Jiang, Q-W

    2016-01-01

    Among the three major schistosome species infecting human beings, Schistosoma japonicum is the only endemic species in The People's Republic of China. Schistosomiasis is endemic in 78 countries and regions and poses a severe threat to public health and socioeconomic development. Through more than 60years of hard work and endeavour, The People's Republic of China has made considerable achievements and reduced the morbidity and prevalence of this disease to the lowest level ever recorded, especially since the introduction of the new integrated control strategy in 2004. This review illustrates the strategies implemented by giving successful examples of schistosomiasis control from the different types of remaining endemic areas. The challenge to control or eliminate S. japonicum is analysed in order to provide useful information to policy makers and scientists. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Gene Therapy to Cure HIV: Where to from Here?

    PubMed

    Johnston, Rowena

    2016-12-01

    A variety of approaches are being tested to cure HIV, but with the exception of the Berlin patient case, none has been successful. The Berlin patient, positive for both HIV and acute myeloid leukemia (AML), received two stem cell transplants from a donor homozygous for the CCR5delta32 mutation. In the 8 years since his second transplant, he has remained free of both HIV and AML. This case provides strong proof-of-principle that a cure for HIV is possible and might be achieved through gene therapy. Several technological barriers must be resolved and are discussed here, including the safe delivery of the intervention throughout the body of the infected person, increased efficiency of gene editing, and avoidance of resistance to the therapy. Delivery of a gene therapy intervention to HIV-infected people around the world will also be a considerable challenge.

  18. Protective Efficacy of Serially Up-Ranked Subdominant CD8+ T Cell Epitopes against Virus Challenges

    PubMed Central

    Roshorm, Yaowaluck; Bridgeman, Anne; Létourneau, Sven; Liljeström, Peter; Potash, Mary Jane; Volsky, David J.; McMichael, Andrew J.; Hanke, Tomáš

    2011-01-01

    Immunodominance in T cell responses to complex antigens like viruses is still incompletely understood. Some data indicate that the dominant responses to viruses are not necessarily the most protective, while other data imply that dominant responses are the most important. The issue is of considerable importance to the rational design of vaccines, particularly against variable escaping viruses like human immunodeficiency virus type 1 and hepatitis C virus. Here, we showed that sequential inactivation of dominant epitopes up-ranks the remaining subdominant determinants. Importantly, we demonstrated that subdominant epitopes can induce robust responses and protect against whole viruses if they are allowed at least once in the vaccination regimen to locally or temporally dominate T cell induction. Therefore, refocusing T cell immune responses away from highly variable determinants recognized during natural virus infection towards subdominant, but conserved regions is possible and merits evaluation in humans. PMID:21625575

  19. Deep sequencing in library selection projects: what insight does it bring?

    PubMed

    Glanville, J; D'Angelo, S; Khan, T A; Reddy, S T; Naranjo, L; Ferrara, F; Bradbury, A R M

    2015-08-01

    High throughput sequencing is poised to change all aspects of the way antibodies and other binders are discovered and engineered. Millions of available sequence reads provide an unprecedented sampling depth able to guide the design and construction of effective, high quality naïve libraries containing tens of billions of unique molecules. Furthermore, during selections, high throughput sequencing enables quantitative tracing of enriched clones and position-specific guidance to amino acid variation under positive selection during antibody engineering. Successful application of the technologies relies on specific PCR reagent design, correct sequencing platform selection, and effective use of computational tools and statistical measures to remove error, identify antibodies, estimate diversity, and extract signatures of selection from the clone down to individual structural positions. Here we review these considerations and discuss some of the remaining challenges to the widespread adoption of the technology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Formation pathways of mesoporous silica nanoparticles with dodecagonal tiling

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

    Sun, Yao; Ma, Kai; Kao, Teresa

    Considerable progress in the fabrication of quasicrystals demonstrates that they can be realized in a broad range of materials. However, the development of chemistries enabling direct experimental observation of early quasicrystal growth pathways remains challenging. Here, we report the synthesis of four surfactant-directed mesoporous silica nanoparticle structures, including dodecagonal quasicrystalline nanoparticles, as a function of micelle pore expander concentration or stirring rate. We demonstrate that the early formation stages of dodecagonal quasicrystalline mesoporous silica nanoparticles can be preserved, where precise control of mesoporous silica nanoparticle size down to <30 nm facilitates comparison between mesoporous silica nanoparticles and simulated single-particle growthmore » trajectories beginning with a single tiling unit. Our results reveal details of the building block size distributions during early growth and how they promote quasicrystal formation. This work identifies simple synthetic parameters, such as stirring rate, that may be exploited to design other quasicrystal-forming self-assembly chemistries and processes.« less

  1. Selective removal of cesium by ammonium molybdophosphate - polyacrylonitrile bead and membrane.

    PubMed

    Ding, Dahu; Zhang, Zhenya; Chen, Rongzhi; Cai, Tianming

    2017-02-15

    The selective removal of radionuclides with extremely low concentrations from environmental medium remains a big challenge. Ammonium molybdophosphate possess considerable selectivity towards cesium ion (Cs + ) due to the specific ion exchange between Cs + and NH 4 + . Ammonium molybdophosphate - polyacrylonitrile (AMP-PAN) membrane was successfully prepared for the first time in this study. Efficient removal of Cs + (95.7%, 94.1% and 91.3% of 1mgL -1 ) from solutions with high ionic strength (400mgL -1 of Na + , Ca 2+ or K + ) was achieved by AMP-PAN composite. Multilayer chemical adsorption process was testified through kinetic and isotherm studies. The estimated maximum adsorption capacities even reached 138.9±21.3mgg -1 . Specifically, the liquid film diffusion was identified as the rate-limiting step throughout the removal process. Finally, AMP-PAN membrane could eliminate Cs + from water effectively through the filtration adsorption process. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease.

    PubMed

    Hoban, Megan D; Orkin, Stuart H; Bauer, Daniel E

    2016-02-18

    Effective medical management for sickle cell disease (SCD) remains elusive. As a prevalent and severe monogenic disorder, SCD has been long considered a logical candidate for gene therapy. Significant progress has been made in moving toward this goal. These efforts have provided substantial insight into the natural regulation of the globin genes and illuminated challenges for genetic manipulation of the hematopoietic system. The initial γ-retroviral vectors, next-generation lentiviral vectors, and novel genome engineering and gene regulation approaches each share the goal of preventing erythrocyte sickling. After years of preclinical studies, several clinical trials for SCD gene therapies are now open. This review focuses on progress made toward achieving gene therapy, the current state of the field, consideration of factors that may determine clinical success, and prospects for future development. © 2016 by The American Society of Hematology.

  3. Improvement of the light-tissue coupling for better outcome of phototherapies

    NASA Astrophysics Data System (ADS)

    da Silva, Dilleys Ferreira; Vollet Filho, José Dirceu; Fortunato, Thereza Cury; Moriyama, Lilian Tan; Grecco, Clovis; Pratavieira, Sebastião.; Kurachi, Cristina; Bagnato, Vanderlei Salvador

    2018-02-01

    Phototherapies have been increasingly used in several applications such as the control of pain and inflammatory processes, photodynamic therapy, and even aesthetics uses. After many decades, the dosimetry for those techniques remains challenging. One of the key issues is the lack of homogeneity obtained for tissue illumination, which may limit adequate treatment. Especially concerning lesions, the surface tissue is usually irregular, and the light does not couple to the tissue efficiently to promote an effective treatment. A series of experiments have been performed using optical phantoms, in which coupling was improved by introducing a gel with a low concentration of scattering agents between the fiber and the phantom as an attempt to improve the homogeneity of light distribution within the phantoms. The effects promoted by roughness on phantom tissue surfaces are considerably attenuated when the coupling gel was introduced, resulting in a more uniform illumination pattern that may be used to promote better phototherapy treatments outcome.

  4. Deep sequencing in library selection projects: what insight does it bring?

    PubMed Central

    Glanville, J; D’Angelo, S; Khan, T.A.; Reddy, S. T.; Naranjo, L.; Ferrara, F.; Bradbury, A.R.M.

    2015-01-01

    High throughput sequencing is poised to change all aspects of the way antibodies and other binders are discovered and engineered. Millions of available sequence reads provide an unprecedented sampling depth able to guide the design and construction of effective, high quality naïve libraries containing tens of billions of unique molecules. Furthermore, during selections, high throughput sequencing enables quantitative tracing of enriched clones and position-specific guidance to amino acid variation under positive selection during antibody engineering. Successful application of the technologies relies on specific PCR reagent design, correct sequencing platform selection, and effective use of computational tools and statistical measures to remove error, identify antibodies, estimate diversity, and extract signatures of selection from the clone down to individual structural positions. Here we review these considerations and discuss some of the remaining challenges to the widespread adoption of the technology. PMID:26451649

  5. Brain metastasis and treatment

    PubMed Central

    Ahluwalia, Manmeet S.; Vogelbaum, Michael V.; Chao, Samuel T.

    2014-01-01

    Despite major therapeutic advances in the management of patients with systemic malignancies, management of brain metastases remains a significant challenge. These patients often require multidisciplinary care that includes surgical resection, radiation therapy, chemotherapy, and targeted therapies. Complex decisions about the sequencing of therapies to control extracranial and intracranial disease require input from neurosurgeons, radiation oncologists, and medical/neuro-oncologists. With advances in understanding of the biology of brain metastases, molecularly defined disease subsets and the advent of targeted therapy as well as immunotherapeutic agents offer promise. Future care of these patients will entail tailoring treatment based on host (performance status and age) and tumor (molecular cytogenetic characteristics, number of metastases, and extracranial disease status) factors. Considerable work involving preclinical models and better clinical trial designs that focus not only on effective control of tumor but also on quality of life and neurocognition needs to be done to improve the outcome of these patients. PMID:25580268

  6. Export of Strongly Diluted Greenland Meltwater From a Major Glacial Fjord

    NASA Astrophysics Data System (ADS)

    Beaird, Nicholas L.; Straneo, Fiammetta; Jenkins, William

    2018-05-01

    The Greenland Ice Sheet has been, and will continue, losing mass at an accelerating rate. The influence of this anomalous meltwater discharge on the regional and large-scale ocean could be considerable but remains poorly understood. This uncertainty is in part a consequence of challenges in observing water mass transformation and meltwater spreading in coastal Greenland. Here we use tracer observations that enable unprecedented quantification of the export, mixing, and vertical distribution of meltwaters leaving one of Greenland's major glacial fjords. We find that the primarily subsurface meltwater input results in the upwelling of the deep fjord waters and an export of a meltwater/deepwater mixture that is 30 times larger than the initial meltwater release. Using these tracer data, the vertical structure of Greenland's summer meltwater export is defined for the first time showing that half the meltwater export occurs below 65 m.

  7. Formation pathways of mesoporous silica nanoparticles with dodecagonal tiling

    DOE PAGES

    Sun, Yao; Ma, Kai; Kao, Teresa; ...

    2017-08-15

    Considerable progress in the fabrication of quasicrystals demonstrates that they can be realized in a broad range of materials. However, the development of chemistries enabling direct experimental observation of early quasicrystal growth pathways remains challenging. Here, we report the synthesis of four surfactant-directed mesoporous silica nanoparticle structures, including dodecagonal quasicrystalline nanoparticles, as a function of micelle pore expander concentration or stirring rate. We demonstrate that the early formation stages of dodecagonal quasicrystalline mesoporous silica nanoparticles can be preserved, where precise control of mesoporous silica nanoparticle size down to <30 nm facilitates comparison between mesoporous silica nanoparticles and simulated single-particle growthmore » trajectories beginning with a single tiling unit. Our results reveal details of the building block size distributions during early growth and how they promote quasicrystal formation. This work identifies simple synthetic parameters, such as stirring rate, that may be exploited to design other quasicrystal-forming self-assembly chemistries and processes.« less

  8. High energy X-ray phase and dark-field imaging using a random absorption mask.

    PubMed

    Wang, Hongchang; Kashyap, Yogesh; Cai, Biao; Sawhney, Kawal

    2016-07-28

    High energy X-ray imaging has unique advantage over conventional X-ray imaging, since it enables higher penetration into materials with significantly reduced radiation damage. However, the absorption contrast in high energy region is considerably low due to the reduced X-ray absorption cross section for most materials. Even though the X-ray phase and dark-field imaging techniques can provide substantially increased contrast and complementary information, fabricating dedicated optics for high energies still remain a challenge. To address this issue, we present an alternative X-ray imaging approach to produce transmission, phase and scattering signals at high X-ray energies by using a random absorption mask. Importantly, in addition to the synchrotron radiation source, this approach has been demonstrated for practical imaging application with a laboratory-based microfocus X-ray source. This new imaging method could be potentially useful for studying thick samples or heavy materials for advanced research in materials science.

  9. Nanowire arrays restore vision in blind mice.

    PubMed

    Tang, Jing; Qin, Nan; Chong, Yan; Diao, Yupu; Yiliguma; Wang, Zhexuan; Xue, Tian; Jiang, Min; Zhang, Jiayi; Zheng, Gengfeng

    2018-03-06

    The restoration of light response with complex spatiotemporal features in retinal degenerative diseases towards retinal prosthesis has proven to be a considerable challenge over the past decades. Herein, inspired by the structure and function of photoreceptors in retinas, we develop artificial photoreceptors based on gold nanoparticle-decorated titania nanowire arrays, for restoration of visual responses in the blind mice with degenerated photoreceptors. Green, blue and near UV light responses in the retinal ganglion cells (RGCs) are restored with a spatial resolution better than 100 µm. ON responses in RGCs are blocked by glutamatergic antagonists, suggesting functional preservation of the remaining retinal circuits. Moreover, neurons in the primary visual cortex respond to light after subretinal implant of nanowire arrays. Improvement in pupillary light reflex suggests the behavioral recovery of light sensitivity. Our study will shed light on the development of a new generation of optoelectronic toolkits for subretinal prosthetic devices.

  10. Superlattices assembled through shape-induced directional binding

    NASA Astrophysics Data System (ADS)

    Lu, Fang; Yager, Kevin G.; Zhang, Yugang; Xin, Huolin; Gang, Oleg

    2015-04-01

    Organization of spherical particles into lattices is typically driven by packing considerations. Although the addition of directional binding can significantly broaden structural diversity, nanoscale implementation remains challenging. Here we investigate the assembly of clusters and lattices in which anisotropic polyhedral blocks coordinate isotropic spherical nanoparticles via shape-induced directional interactions facilitated by DNA recognition. We show that these polyhedral blocks--cubes and octahedrons--when mixed with spheres, promote the assembly of clusters with architecture determined by polyhedron symmetry. Moreover, three-dimensional binary superlattices are formed when DNA shells accommodate the shape disparity between nanoparticle interfaces. The crystallographic symmetry of assembled lattices is determined by the spatial symmetry of the block's facets, while structural order depends on DNA-tuned interactions and particle size ratio. The presented lattice assembly strategy, exploiting shape for defining the global structure and DNA-mediation locally, opens novel possibilities for by-design fabrication of binary lattices.

  11. The role of myocardial viability in contemporary cardiac practice.

    PubMed

    Jamiel, Abdelrahman; Ebid, Mohamad; Ahmed, Amjad M; Ahmed, Dalia; Al-Mallah, Mouaz H

    2017-07-01

    Ischemic heart disease (IHD) remains the single most common cause of death worldwide. Ischemic cardiomyopathy is a major sequel of coronary artery disease. The economic health burden of IHD is substantial. In patients with old myocardial infarction (OMI), the extent of viable myocardium (VM) directly affects the short- and long-term outcome. There is a considerable collection of observational data showing substantial improvement in patients with significant left ventricular dysfunction when the need for revascularization is guided by preoperative assessment of viability and hibernation. However, a major challenge for present cardiovascular imaging is to identify better ways to assess viable but inadequately perfused myocardium and thus optimize selection of patients for coronary revascularization. Several non-invasive techniques have been developed to detect signs of viability. Hence, our aim is to provide the reader a state-of-the art review for the assessment of myocardial viability.

  12. Factors affecting choice of a healthy lifestyle: implications for nurses.

    PubMed

    Ochieng, Bertha M N

    2006-02-01

    Living a healthy lifestyle still remains a challenge to a wide section of the population. This article argues that since a healthy lifestyle is associated with other aspects of economic and social life, it should be examined within this context. This perspective suggests that participation in a healthy lifestyle, with its behavioural emphasis, which typically involves decisions about food, exercise, smoking, alcohol, drug use, risk of infection and accidents, is not necessarily up to the individual. Socioeconomic status, level of education, family, kin and social networks, gender, age and interpersonal influences all affect the choice of lifestyle. This has implications for community practitioners working in the field of health promotion, in particular to promote healthy lifestyle. A correlation model is presented that can be used by practitioners to identity factors that should be taken into consideration when working with clients to enable them to make a healthy lifestyle the easier option.

  13. Cell death induced by ozone and various non-thermal plasmas: therapeutic perspectives and limitations

    PubMed Central

    Lunov, Oleg; Zablotskii, Vitalii; Churpita, Olexander; Chánová, Eliška; Syková, Eva; Dejneka, Alexandr; Kubinová, Šárka

    2014-01-01

    Non-thermal plasma has been recognized as a promising tool across a vast variety of biomedical applications, with the potential to create novel therapeutic methods. However, the understanding of the molecular mechanisms behind non-thermal plasma cellular effects remains a significant challenge. In this study, we show how two types of different non-thermal plasmas induce cell death in mammalian cell cultures via the formation of multiple intracellular reactive oxygen/nitrogen species. Our results showed a discrepancy in the superoxide accumulation and lysosomal activity in response to air and helium plasma, suggesting that triggered signalling cascades might be grossly different between different plasmas. In addition, the effects of ozone, a considerable component of non-thermal plasma, have been simultaneously evaluated and have revealed much faster and higher cytotoxic effects. Our findings offer novel insight into plasma-induced cellular responses, and provide a basis for better controlled biomedical applications. PMID:25410636

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

    Lu, Fang; Yager, Kevin G.; Zhang, Yugang

    Organization of spherical particles into lattices is typically driven by packing considerations. Although the addition of directional binding can significantly broaden structural diversity, nanoscale implementation remains challenging. Here we investigate the assembly of clusters and lattices in which anisotropic polyhedral blocks coordinate isotropic spherical nanoparticles via shape-induced directional interactions facilitated by DNA recognition. We show that these polyhedral blocks—cubes and octahedrons—when mixed with spheres, promote the assembly of clusters with architecture determined by polyhedron symmetry. Moreover, three-dimensional binary superlattices are formed when DNA shells accommodate the shape disparity between nanoparticle interfaces. The crystallographic symmetry of assembled lattices is determined bymore » the spatial symmetry of the block’s facets, while structural order depends on DNA-tuned interactions and particle size ratio. Lastly, the presented lattice assembly strategy, exploiting shape for defining the global structure and DNA-mediation locally, opens novel possibilities for by-design fabrication of binary lattices.« less

  15. NMR Studies of Low-Gamma Nuclei in Solids

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

    Wasylishen, Roderick E.; Forgeron, Michelle A.; Siegel, Renee

    2006-07-24

    Over the past five years we have devoted considerable time to solid-state NMR investigaitons of nuclei, which are traditionally known as "difficult" because of their small magnetic moments. These include quadrupolar nuclei such as 35Cl, 53 Cr, 91Zr, 95Mo, 99Ru, 131 Xe, as well as spin-1/2 nuclei such as 109Ag. While NMR studies of such isotopes remain challenging, the use of moderate to high magnetic field strengths together with a variety of enhancement techniques is leading to many interesting applications. In this talk some of our successes in studying these isotopes will be presented. For example, we will present preliminarymore » results of 131Xe NMR studies of solid sodium perxenate, as well as 109Ag NMR studies of silver dialkylphosphites. Our experience using population enhancement techniques that utilize hyperbolic secant pulses will also be discussed.« less

  16. Analyzing bat migration

    USGS Publications Warehouse

    Cryan, Paul M.; Diehl, Robert H.

    2009-01-01

    T HE MIGRATORY MOVEIvl.ENTS OF BATS have proven ex­ tremely difficult to determine. Despite extensive efforts during the past century to track the movements of bats across landscapes, efficient methods of following small- to medium-size volant animals <240 gl for extended periods (>8 weeks) over long distances (>100 km) have not been developed. Important questions about bat migration remain unanswered: Which bats migrate? Where do they go? How far do they move? How high and fast do they fly? What are their habitat needs during migration? How do bats orient and navigate during migration? Addressing these apparently simple questions will be a considerable challenge to anyone interested in advancing the study of bat migration. In this chapter, we present direct and indirect methods used to study bat migration as well as techniques that have worked for studying bird migration that could feasibly be adapted to the study of bats.

  17. White Light Emission from Cucurbituril-Based Host-Guest Interaction in the Solid State: New Function of the Macrocyclic Host.

    PubMed

    Xia, Yu; Chen, Shiyan; Ni, Xin-Long

    2018-04-18

    Energy transfer and interchange are central for fabricating white light-emitting organic materials. However, increasing the efficiency of light energy transfer remains a considerable challenge because of the occurrence of "cross talk". In this work, by exploiting the unique photophysical properties of cucurbituril-triggered host-guest interactions, the two complementary luminescent colors blue and yellow for white light emission were independently obtained from a single fluorophore dye rather than energy transfer. Further study suggested that the rigid cavity of cucurbiturils efficiently prevented the aggregation of the dye and improved its thermal stability in the solid state by providing a regular nanosized fence for each encapsulated dye molecule. As a result, a novel macrocycle-assisted supramolecular approach for obtaining solid, white light-emitting organic materials with low cost, high efficiency, and easy scale-up was successfully demonstrated.

  18. Delivering proportionate governance in the era of eHealth

    PubMed Central

    Sethi, Nayha; Laurie, Graeme T.

    2013-01-01

    This article advances a principled proportionate governance model (PPGM) that overcomes key impediments to using health records for research. Despite increasing initiatives for maximising benefits of data linkage, significant challenges remain, including a culture of caution around data sharing and linkage, failure to make use of flexibilities within the law and failure to incorporate intelligent iterative design. The article identifies key issues for consideration and posits a flexible and accessible governance model that provides a robust and efficient means of paying due regard to both privacy and the public interests in research. We argue that proportionate governance based on clear guiding principles accurately gauges risks associated with data uses and assigns safeguards accordingly. This requires a clear articulation of roles and responsibilities at all levels of decision-making and effective training for researchers and data custodians. Accordingly, the PPGM encourages and supports defensible judgements about data linkage in the public interest. PMID:24634569

  19. Inner Speech: Development, Cognitive Functions, Phenomenology, and Neurobiology

    PubMed Central

    2015-01-01

    Inner speech—also known as covert speech or verbal thinking—has been implicated in theories of cognitive development, speech monitoring, executive function, and psychopathology. Despite a growing body of knowledge on its phenomenology, development, and function, approaches to the scientific study of inner speech have remained diffuse and largely unintegrated. This review examines prominent theoretical approaches to inner speech and methodological challenges in its study, before reviewing current evidence on inner speech in children and adults from both typical and atypical populations. We conclude by considering prospects for an integrated cognitive science of inner speech, and present a multicomponent model of the phenomenon informed by developmental, cognitive, and psycholinguistic considerations. Despite its variability among individuals and across the life span, inner speech appears to perform significant functions in human cognition, which in some cases reflect its developmental origins and its sharing of resources with other cognitive processes. PMID:26011789

  20. Renewed Global Partnerships and Redesigned Roadmaps for Rabies Prevention and Control

    PubMed Central

    Lembo, Tiziana; Attlan, Michaël; Bourhy, Hervé; Cleaveland, Sarah; Costa, Peter; de Balogh, Katinka; Dodet, Betty; Fooks, Anthony R.; Hiby, Elly; Leanes, Fernando; Meslin, François-Xavier; Miranda, Mary Elizabeth; Müller, Thomas; Nel, Louis H.; Rupprecht, Charles E.; Tordo, Noël; Tumpey, Abbigail; Wandeler, Alexander; Briggs, Deborah J.

    2011-01-01

    Canine rabies, responsible for most human rabies deaths, is a serious global public health concern. This zoonosis is entirely preventable, but by focusing solely upon rabies prevention in humans, this “incurable wound” persists at high costs. Although preventing human deaths through canine rabies elimination is feasible, dog rabies control is often neglected, because dogs are not considered typical economic commodities by the animal health sector. Here, we demonstrate that the responsibility of managing rabies falls upon multiple sectors, that a truly integrated approach is the key to rabies elimination, and that considerable progress has been made to this effect. Achievements include the construction of global rabies networks and organizational partnerships; development of road maps, operational toolkits, and a blueprint for rabies prevention and control; and opportunities for scaling up and replication of successful programs. Progress must continue towards overcoming the remaining challenges preventing the ultimate goal of rabies elimination. PMID:21776359

  1. Formulation and treatment: integrating religion and spirituality in clinical practice.

    PubMed

    Josephson, Allan M

    2004-01-01

    Developing scientifically sound and clinically meaningful case formulations is so challenging that it may verge on becoming a "lost art." Pressures (scientific, economic, and cultural) remain that prevent child and adolescent psychiatrists from getting a complete understanding of the patient and family. Including a strong consideration of data related to religion, spirituality, and worldview may seem only to complicate an already arduous task. The clinician who includes these factors in treatment is faced with decisions of when to discuss these issues, how to discuss them and in what depth, and finally, when to refer to a religious/spiritual professional. Nonetheless, the importance of these factors in the lives of many children and families leaves no option but to address them as directly as possible. It is well worth the effort and, in many cases, will open new areas for clinical improvement in patients.

  2. Genomic landscape of gastric cancer: molecular classification and potential targets.

    PubMed

    Guo, Jiawei; Yu, Weiwei; Su, Hui; Pang, Xiufeng

    2017-02-01

    Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumorigenesis hinders the development of therapeutic strategies. However, ongoing collaborative sequencing efforts facilitate molecular classification and unveil the genomic landscape of gastric cancer. Several new drivers and tumorigenic pathways in gastric cancer, including chromatin remodeling genes, RhoA-related pathways, TP53 dysregulation, activation of receptor tyrosine kinases, stem cell pathways and abnormal DNA methylation, have been revealed. These newly identified genomic alterations await translation into clinical diagnosis and targeted therapies. Considering that loss-of-function mutations are intractable, synthetic lethality could be employed when discussing feasible therapeutic strategies. Although many challenges remain to be tackled, we are optimistic regarding improvements in the prognosis and treatment of gastric cancer in the near future.

  3. Validating a Model for Welding Induced Residual Stress Using High-Energy X-ray Diffraction

    NASA Astrophysics Data System (ADS)

    Mach, J. C.; Budrow, C. J.; Pagan, D. C.; Ruff, J. P. C.; Park, J.-S.; Okasinski, J.; Beaudoin, A. J.; Miller, M. P.

    2017-05-01

    Integrated computational materials engineering (ICME) provides a pathway to advance performance in structures through the use of physically-based models to better understand how manufacturing processes influence product performance. As one particular challenge, consider that residual stresses induced in fabrication are pervasive and directly impact the life of structures. For ICME to be an effective strategy, it is essential that predictive capability be developed in conjunction with critical experiments. In the present work, simulation results from a multi-physics model for gas metal arc welding are evaluated through x-ray diffraction using synchrotron radiation. A test component was designed with intent to develop significant gradients in residual stress, be representative of real-world engineering application, yet remain tractable for finely spaced strain measurements with positioning equipment available at synchrotron facilities. The experimental validation lends confidence to model predictions, facilitating the explicit consideration of residual stress distribution in prediction of fatigue life.

  4. A complete heart block in a young male: a case report and review of literature of cardiac sarcoidosis.

    PubMed

    Patel, Brijesh; Shah, Mahek; Gelaye, Alehegn; Dusaj, Raman

    2017-01-01

    Cardiac sarcoidosis is one of the uncommon causes of heart failure. Generally, it presents in the form of varying clinical manifestations ranging from asymptomatic to fatal arrhythmias such as ventricular tachycardia and complete heart block. It is difficult to make a diagnosis strictly based on clinical grounds. However, in the setting of extracardiac sarcoidosis and patients presenting with advanced heart block or ventricular arrhythmia, direct cardiac involvement should be suspected. The definitive diagnosis of cardiac sarcoidosis can be made from endomyocardial biopsy, but it is falling out of favor due to patchy myocardial involvement, considerable procedure-related risks, and advancement in additional imaging modalities. Once cardiac sarcoidosis has been diagnosed, management of the disease remains challenging. Steroids are considered the mainstay of therapy, and implantable cardioverter defibrillator therapy can be considered in a selected group of patients at greater risk for malignant ventricular arrhythmias.

  5. In Search of Search Engine Marketing Strategy Amongst SME's in Ireland

    NASA Astrophysics Data System (ADS)

    Barry, Chris; Charleton, Debbie

    Researchers have identified the Web as a searchers first port of call for locating information. Search Engine Marketing (SEM) strategies have been noted as a key consideration when developing, maintaining and managing Websites. A study presented here of SEM practices of Irish small to medium enterprises (SMEs) reveals they plan to spend more resources on SEM in the future. Most firms utilize an informal SEM strategy, where Website optimization is perceived most effective in attracting traffic. Respondents cite the use of ‘keywords in title and description tags’ as the most used SEM technique, followed by the use of ‘keywords throughout the whole Website’; while ‘Pay for Placement’ was most widely used Paid Search technique. In concurrence with the literature, measuring SEM performance remains a significant challenge with many firms unsure if they measure it effectively. An encouraging finding is that Irish SMEs adopt a positive ethical posture when undertaking SEM.

  6. Stretchable liquid-crystal blue-phase gels.

    PubMed

    Castles, F; Morris, S M; Hung, J M C; Qasim, M M; Wright, A D; Nosheen, S; Choi, S S; Outram, B I; Elston, S J; Burgess, C; Hill, L; Wilkinson, T D; Coles, H J

    2014-08-01

    Liquid-crystalline polymers are materials of considerable scientific interest and technological value. An important subset of these materials exhibit rubber-like elasticity, combining the optical properties of liquid crystals with the mechanical properties of rubber. Moreover, they exhibit behaviour not seen in either type of material independently, and many of their properties depend crucially on the particular mesophase employed. Such stretchable liquid-crystalline polymers have previously been demonstrated in the nematic, chiral-nematic, and smectic mesophases. Here, we report the fabrication of a stretchable gel of blue phase I, which forms a self-assembled, three-dimensional photonic crystal that remains electro-optically switchable under a moderate applied voltage, and whose optical properties can be manipulated by an applied strain. We also find that, unlike its undistorted counterpart, a mechanically deformed blue phase exhibits a Pockels electro-optic effect, which sets out new theoretical challenges and possibilities for low-voltage electro-optic devices.

  7. From sensation to perception: Using multivariate classification of visual illusions to identify neural correlates of conscious awareness in space and time.

    PubMed

    Hogendoorn, Hinze

    2015-01-01

    An important goal of cognitive neuroscience is understanding the neural underpinnings of conscious awareness. Although the low-level processing of sensory input is well understood in most modalities, it remains a challenge to understand how the brain translates such input into conscious awareness. Here, I argue that the application of multivariate pattern classification techniques to neuroimaging data acquired while observers experience perceptual illusions provides a unique way to dissociate sensory mechanisms from mechanisms underlying conscious awareness. Using this approach, it is possible to directly compare patterns of neural activity that correspond to the contents of awareness, independent from changes in sensory input, and to track these neural representations over time at high temporal resolution. I highlight five recent studies using this approach, and provide practical considerations and limitations for future implementations.

  8. Management of metastatic renal cell carcinoma patients with poor-risk features: current status and future perspectives.

    PubMed

    Santoni, Matteo; De Tursi, Michele; Felici, Alessandra; Lo Re, Giovanni; Ricotta, Riccardo; Ruggeri, Enzo Maria; Sabbatini, Roberto; Santini, Daniele; Vaccaro, Vanja; Milella, Michele

    2013-06-01

    With seven agents approved for renal cell carcinoma within the past few years, there has undoubtedly been progress in treating this disease. However, patients with poor-risk features remain a challenging and difficult-to-treat population, with the mTOR inhibitor, temsirolimus, the only agent approved in the first-line setting. Phase III trial data are still lacking VEGF-pathway inhibitors in patients with poor prognostic features. Poor-risk patients need to be considered as a heterogeneous population. Further understanding of biomarkers can lead to a better selection of patients who may benefit the most from treatment and improvements in prognosis. The presence of poor Karnofsky scores and liver or CNS disease may affect the outcome of these patients much more than other identified factors. This consideration may provide the rationale to further stratify poor-risk patients further subgroups destined to receive either cure or palliation.

  9. Heat and Health in a Changing Climate: Building a Decision Support Tool for California Public Health Officials

    NASA Astrophysics Data System (ADS)

    Steinberg, N.

    2017-12-01

    There is considerable interest in overlaying climate projections with social vulnerability maps as a mechanism for targeting community adaptation efforts. Yet the identification of relevant factors for adaptation- and resilience-based decisions remain a challenge. Our findings show that successful adaptation interventions are more likely when factors are grouped and spatially represented. By designing a decision-support tool that is focused on informing long-term planning to mitigate the public health impacts of extreme heat, communities can more easily integrate climate, land use, and population characteristics into local planning processes. The ability to compare risks and potential health impacts across census tracts may also position local practitioners to leverage scarce resources. This presentation will discuss the information gaps identified by planners and public health practitioners throughout California and illustrate the spatial variations of key health risk factors.

  10. Superlattices assembled through shape-induced directional binding

    DOE PAGES

    Lu, Fang; Yager, Kevin G.; Zhang, Yugang; ...

    2015-04-23

    Organization of spherical particles into lattices is typically driven by packing considerations. Although the addition of directional binding can significantly broaden structural diversity, nanoscale implementation remains challenging. Here we investigate the assembly of clusters and lattices in which anisotropic polyhedral blocks coordinate isotropic spherical nanoparticles via shape-induced directional interactions facilitated by DNA recognition. We show that these polyhedral blocks—cubes and octahedrons—when mixed with spheres, promote the assembly of clusters with architecture determined by polyhedron symmetry. Moreover, three-dimensional binary superlattices are formed when DNA shells accommodate the shape disparity between nanoparticle interfaces. The crystallographic symmetry of assembled lattices is determined bymore » the spatial symmetry of the block’s facets, while structural order depends on DNA-tuned interactions and particle size ratio. Lastly, the presented lattice assembly strategy, exploiting shape for defining the global structure and DNA-mediation locally, opens novel possibilities for by-design fabrication of binary lattices.« less

  11. Protection of non-human primates against rabies with an adenovirus recombinant vaccine

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

    Xiang, Z.Q.; Greenberg, L.; Ertl, H.C., E-mail: ertl@wistar.upenn.edu

    Rabies remains a major neglected global zoonosis. New vaccine strategies are needed for human rabies prophylaxis. A single intramuscular immunization with a moderate dose of an experimental chimpanzee adenovirus (Ad) vector serotype SAd-V24, also termed AdC68, expressing the rabies virus glycoprotein, resulted in sustained titers of rabies virus neutralizing antibodies and protection against a lethal rabies virus challenge infection in a non-human primate model. Taken together, these data demonstrate the safety, immunogenicity, and efficacy of the recombinant Ad-rabies vector for further consideration in human clinical trials. - Highlights: • Pre-exposure vaccination with vaccine based on a chimpanzee derived adenovirus protectsmore » against rabies. • Protection is sustained. • Protection is achieved with single low-dose of vaccine given intramuscularly. • Protection is not affected by pre-existing antibodies to common human serotypes of adenovirus.« less

  12. Implementation of psychiatric-focused lifestyle medicine programs in Asia.

    PubMed

    Sarris, Jerome; Nishi, Daisuke; Xiang, Yu-Tao; Su, Kuan-Pin; Bannatyne, Amy; Oliver, Georgina; Kua, Ee-Heok; Ng, Chee Hong

    2015-12-01

    Lifestyle-focused health programs are growing in interest throughout Western society, and a range of lifestyle factors are known to enhance both physical and mental health. However, it remains largely unknown as to whether this approach is salient for the Asian context. The major components of integrative lifestyle-focused health programs to enhance mental and physical health are considered to include the evidence-based adoption of physical activity and exercise, dietary modification, general psychoeducation, adequate relaxation/sleep and social interaction, use of mindfulness techniques, the reduction of substance use, attention of intersecting environmental factors, and the potential use of motivation and goal-setting techniques. This paper outlines an overview of the evidence underpinning these elements, and discusses potential barriers and challenges, and what logistical considerations may need to be addressed in the implementation of such programs within the context of Asian cultures. © 2015 Wiley Publishing Asia Pty Ltd.

  13. Opportunities for Intervention Strategies for Weight Management: Global Actions on Fluid Intake Patterns

    PubMed Central

    Lafontan, Max; Visscher, Tommy L.S.; Farpour-Lambert, Nathalie; Yumuk, Volkan

    2015-01-01

    Water is an essential nutrient for all physiological functions and particularly important for thermoregulation. About 60% of our body weight is made of water. Under standard conditions (18-20 °C and moderate activity), water balance is regulated within 0.2 % of body weight over a 24-hour period. Water requirement varies between individuals and according to environmental conditions. Concerning considerations related to obesity, the health impact of fluid intake is commonly overlooked. Fluid intake advices are missing in most of food pyramids offered to the public, and water requirements and hydration challenges remain often neglected. The purpose of this paper is to emphasize and discuss the role of water consumption in the context of other important public health measures for weight management. Attention will be focused on fluid intake patterns and hydration-related questions in the context of global interventions and/or physical activity programs settled in weight management protocols. PMID:25765164

  14. Elucidation of high sensitivity of δ-HMX: New insight from first principles simulations

    NASA Astrophysics Data System (ADS)

    Kuklja, Maija M.; Tsyshevsky, Roman V.; Sharia, Onise

    2017-01-01

    Understanding of a significant difference in sensitivities of β and δ phases of cyclotetramethylene-tetranitramine (HMX) has been long one of the challenges in the field of high energy density materials. Despite many experimental and theoretical efforts to explain the high sensitivity of the δ phase, convincing reasons behind the HMX behavior remained unclear. We established that the presence of a polar surface in δ-HMX has fundamental implications for stability and overall chemical behavior of the material. A comparative quantum-chemical analysis of decomposition mechanisms in polar δ-HMX and nonpolar β-HMX discovered a considerable difference in dominating dissociation reactions, activation barriers, and reaction rates. The polarization-induced charge transfer offered a logical explanation for different sensitivity of β-HMX and δ-HMX polymorphs to detonation initiation. Our conclusions also removed long-standing contradictions and explained a large range of experimental data on thermal decomposition of HMX.

  15. Fathers' Investments of Money and Time Across Residential Contexts.

    PubMed

    Carlson, Marcia J; VanOrman, Alicia G; Turner, Kimberly J

    2017-02-01

    Fathers' roles in family life have changed dramatically over the past 50 years. In addition to ongoing breadwinning responsibilities, many fathers are now involved in direct caregiving and engagement with children. Yet there is considerable variation in what fathers do, especially depending on whether they live with or away from their child. In this article, the authors use data from the Fragile Families and Child Wellbeing Study (N = 3,869) to describe how fathers' economic capacities (money) and direct involvement with children (time) are associated over child ages 1 to 9 for resident versus nonresident fathers, net of confounding factors. They found suggestive evidence that money and time investments operate differently across residential contexts: Resident fathers experience a trade-off between market work and time involved with children. In contrast, nonresident fathers' higher economic capacities are associated with more time involvement, underscoring the greater challenge for such fathers to remain actively involved.

  16. Beyond Utterances: Distributed Cognition as a Framework for Studying Discourse in Adults with Acquired Brain Injury

    PubMed Central

    Duff, Melissa C.; Mutlu, Bilge; Byom, Lindsey; Turkstra, Lyn S.

    2014-01-01

    Considerable effort has been directed at understanding the nature of the communicative deficits observed in individuals with acquired brain injuries. Yet several theoretical, methodological, and clinical challenges remain. In this article, we examine distributed cognition as a framework for understanding interaction among communication partners, interaction of communication and cognition, and interaction with the environments and contexts of everyday language use. We review the basic principles of distributed cognition and the implications for applying this approach to the study of discourse in individuals with cognitive-communication disorders. We also review a range of protocols and findings from our research that highlight how the distributed cognition approach might offer a deeper understanding of communicative mechanisms and deficits in individuals with cognitive communication impairments. The advantages and implications of distributed cognition as a framework for studying discourse in adults with acquired brain injury are discussed. PMID:22362323

  17. Adaptation workbook: Chapter 3

    Treesearch

    Maria Janowiak; Patricia Butler; Chris Swanston; Linda Parker; Matt St. Pierre; Leslie Brandt

    2012-01-01

    Climate change imposes many challenges on the long-term management of ecosystems and is becoming an increasingly important consideration in land management planning and decisionmaking at a variety of spatial scales. The process outlined in this chapter helps managers incorporate climate change considerations into management planning and activities, while complementing...

  18. 75 FR 10822 - Notice of the March 24, 2010 Millennium Challenge Corporation Board of Directors Meeting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ... MILLENNIUM CHALLENGE CORPORATION [MCC FR 10-03] Notice of the March 24, 2010 Millennium Challenge... and Date: 10 a.m. to 12 p.m., Wednesday, March 24, 2010. Place: Department of State, 2201 C Street, NW... consideration of classified information and the meeting will be closed to the public. Dated: March 5, 2010...

  19. Methodological Challenges in Studies Examining the Effects of Breakfast on Cognitive Performance and Appetite in Children and Adolescents.

    PubMed

    Adolphus, Katie; Bellissimo, Nick; Lawton, Clare L; Ford, Nikki A; Rains, Tia M; Totosy de Zepetnek, Julia; Dye, Louise

    2017-01-01

    Breakfast is purported to confer a number of benefits on diet quality, health, appetite regulation, and cognitive performance. However, new evidence has challenged the long-held belief that breakfast is the most important meal of the day. This review aims to provide a comprehensive discussion of the key methodological challenges and considerations in studies assessing the effect of breakfast on cognitive performance and appetite control, along with recommendations for future research. This review focuses on the myriad challenges involved in studying children and adolescents specifically. Key methodological challenges and considerations include study design and location, sampling and sample section, choice of objective cognitive tests, choice of objective and subjective appetite measures, merits of providing a fixed breakfast compared with ad libitum, assessment and definition of habitual breakfast consumption, transparency of treatment condition, difficulty of isolating the direct effects of breakfast consumption, untangling acute and chronic effects, and influence of confounding variables. These methodological challenges have hampered a clear substantiation of the potential positive effects of breakfast on cognition and appetite control and contributed to the debate questioning the notion that breakfast is the most important meal of the day. © 2017 American Society for Nutrition.

  20. Methodological Challenges in Studies Examining the Effects of Breakfast on Cognitive Performance and Appetite in Children and Adolescents123

    PubMed Central

    Bellissimo, Nick; Ford, Nikki A; Rains, Tia M

    2017-01-01

    Breakfast is purported to confer a number of benefits on diet quality, health, appetite regulation, and cognitive performance. However, new evidence has challenged the long-held belief that breakfast is the most important meal of the day. This review aims to provide a comprehensive discussion of the key methodological challenges and considerations in studies assessing the effect of breakfast on cognitive performance and appetite control, along with recommendations for future research. This review focuses on the myriad challenges involved in studying children and adolescents specifically. Key methodological challenges and considerations include study design and location, sampling and sample section, choice of objective cognitive tests, choice of objective and subjective appetite measures, merits of providing a fixed breakfast compared with ad libitum, assessment and definition of habitual breakfast consumption, transparency of treatment condition, difficulty of isolating the direct effects of breakfast consumption, untangling acute and chronic effects, and influence of confounding variables. These methodological challenges have hampered a clear substantiation of the potential positive effects of breakfast on cognition and appetite control and contributed to the debate questioning the notion that breakfast is the most important meal of the day. PMID:28096143

  1. Primary tuberculosis of the middle ear cleft: diagnostic and therapeutic considerations.

    PubMed

    Liktor, Balázs; Liktor, Bálint; Liktor, Bálint; Kálmán, Judit; Horváth, Barnabás; Sziklai, István; Karosi, Tamás

    2014-07-01

    Tuberculosis remains one of the most challenging infectious diseases, which rarely manifests in the middle ear cleft exclusively. Typical symptoms of tuberculosis have become more and more confusing due to the genetic evolution of different Mycobacterium species. In the diagnosis of tuberculous otitis media (TOM), clinical suspicion plays a fundamental role, when topical and/or systemic antibiotic treatment cannot lead to improvement in ear discharge and inflammation. If there is no other reason of persisting otorrhea, microbiological sampling and culturing are the subsequent steps of diagnosis. These investigations, however, have low sensitivity; therefore a canal wall-up mastoidectomy is recommended, which includes the removal of necrotic bone and multiple histological sampling from various locations. Currently, histopathological analysis is the most robust and reliable method in the diagnosis of TOM. Tuberculin skin test, Mycobacterium-specific PCR and interferon-gamma release assay cannot distinguish between active, inactive or post-infective conditions. According to these considerations, these methods may serve as supplementary assays for the final diagnosis. Having the appropriate diagnosis after surgical intervention and laboratory analysis, medical management should be continued by anti-tuberculosis chemotherapy. Hereby, we demonstrate two cases with primary TOM and provide an overview of the literature in the light of diagnostic and therapeutic guidelines in the management of TOM.

  2. Coordinated regulation of growth, activity and transcription in natural populations of the unicellular nitrogen-fixing cyanobacterium Crocosphaera.

    PubMed

    Wilson, Samuel T; Aylward, Frank O; Ribalet, Francois; Barone, Benedetto; Casey, John R; Connell, Paige E; Eppley, John M; Ferrón, Sara; Fitzsimmons, Jessica N; Hayes, Christopher T; Romano, Anna E; Turk-Kubo, Kendra A; Vislova, Alice; Armbrust, E Virginia; Caron, David A; Church, Matthew J; Zehr, Jonathan P; Karl, David M; DeLong, Edward F

    2017-07-31

    The temporal dynamics of phytoplankton growth and activity have large impacts on fluxes of matter and energy, yet obtaining in situ metabolic measurements of sufficient resolution for even dominant microorganisms remains a considerable challenge. We performed Lagrangian diel sampling with synoptic measurements of population abundances, dinitrogen (N 2 ) fixation, mortality, productivity, export and transcription in a bloom of Crocosphaera over eight days in the North Pacific Subtropical Gyre (NPSG). Quantitative transcriptomic analyses revealed clear diel oscillations in transcript abundances for 34% of Crocosphaera genes identified, reflecting a systematic progression of gene expression in diverse metabolic pathways. Significant time-lagged correspondence was evident between nifH transcript abundance and maximal N 2 fixation, as well as sepF transcript abundance and cell division, demonstrating the utility of transcriptomics to predict the occurrence and timing of physiological and biogeochemical processes in natural populations. Indirect estimates of carbon fixation by Crocosphaera were equivalent to 11% of net community production, suggesting that under bloom conditions this diazotroph has a considerable impact on the wider carbon cycle. Our cross-scale synthesis of molecular, population and community-wide data underscores the tightly coordinated in situ metabolism of the keystone N 2 -fixing cyanobacterium Crocosphaera, as well as the broader ecosystem-wide implications of its activities.

  3. Scalp reconstruction: an algorithmic approach and systematic review.

    PubMed

    Desai, Shaun C; Sand, Jordan P; Sharon, Jeffrey D; Branham, Gregory; Nussenbaum, Brian

    2015-01-01

    Reconstruction of the scalp after acquired defects remains a common challenge for the reconstructive surgeon, especially in a patient with a history of radiation to the area. To review the current literature and describe a novel algorithm to help guide the reconstructive surgeon in determining the optimal reconstruction from a cosmetic and functional standpoint. Pertinent surgical anatomy, considerations for patient and technique selection, reconstructive goals, as well as the reconstructive ladder, are also discussed. A PubMed and Medline search was performed of the entire English literature with respect to scalp reconstruction. Priority of review was given to those studies with higher-quality levels of evidence. Size, location, radiation history, and potential for hairline distortion are important factors in determining the ideal reconstruction. The tighter and looser areas of the scalp play a major role in the potential for primary or local flap closure. Patients with medium to large defects and a history of radiation will likely benefit from free tissue transfer. Ideal reconstruction of scalp defects relies on a comprehensive understanding of scalp anatomy, a full consideration of the armamentarium of surgical techniques, and a detailed appraisal of patient factors and expectations. The simplest reconstruction should be used whenever possible to provide the most functional and aesthetic scalp reconstruction, with the least amount of complexity. NA.

  4. Teaching epidemiology in the digital age: considerations for academicians and their students.

    PubMed

    Caron, Rosemary M

    2013-09-01

    The way in which we prepare future public health professionals is changing because of the digital age. Online education is expanding the accessibility of public health training to students and practitioners with diverse backgrounds. Online courses offer many advantages for students, including flexible schedules, elimination of commuting time, and fostering interactions among students and the instructor. A few disadvantages of online courses for the student can include a feeling of isolation, difficulty adjusting to the time-intensive nature, and the required self-discipline to regularly tend to online course materials that immature and working students can find challenging. For faculty who are faced with teaching epidemiology in these changing times of the traditional face-to-face classroom and the virtual classroom, the core teaching principles of this science of public health remain unchanged, yet how they are delivered in the online environment adds a layer of complexity not previously encountered. This paper presents practical considerations for faculty who will be teaching online and their students who will be learning online. In addition, a framework for an online epidemiology course is presented as a model by which faculty interested in teaching epidemiology online can modify the course structure, content, and assessment tools to fit their needs. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Advanced Reading Comprehension Expectations in Secondary School: Considerations for Students with Emotional or Behavior Disorders

    PubMed Central

    Ciullo, Stephen; Ortiz, Miriam B.; Al Otaiba, Stephanie; Lane, Kathleen Lynne

    2015-01-01

    The debate around recent implementation of the Common Core Standards (CCSS) has perplexed many policy makers, practitioners, and researchers; yet there remains broad agreement for the need to improve reading outcomes and college and career readiness for all students, including students with disabilities. One of the most vulnerable populations with disabilities in terms of college and career readiness is students with emotional disorders (ED). A considerable percentage of students with ED encounter unfavorable academic and long-term outcomes, often due to reading difficulties and behavioral variables that impede learning. To date, the impact of rising expectations in reading on the education of students with ED has been absent from this conversation about CCSS. In this article, we consider the implications of new reading expectations in the critical period of Grades 6-12 for students with ED. First, we summarize grade level expectations of the standards. Then, we describe the characteristics and underachievement of students with ED. Next, we evaluate challenges in meeting the expectations based on extant research, and provide recommendations for practice based on the intervention literature. We conclude by prioritizing a research and policy agenda that advocates for increasing the likelihood of success in reading for students with ED in middle school and high school. PMID:27403040

  6. Challenges and Considerations When Conducting an Online Course.

    ERIC Educational Resources Information Center

    Leh, Amy Sheng Chieh; Som, Yahya Mat

    This paper reports challenges of and suggestions for conducting online courses, focusing on the following areas: (1) instructional format, including transferring classroom activities to online activities without affecting students' concentration, motivation, thought, mastery, and comprehension; (2) methods of instruction, including developing an…

  7. Review of geochemical reference sample programs since G-1 and W-1: progress to date and remaining challenges

    USGS Publications Warehouse

    Kane, J.S.

    1991-01-01

    A brief history of programs to develop geochemical reference samples and certified reference samples for use in geochemical analysis is presented. While progress has been made since G-1 and W-1 were issued, many challenges remain. ?? 1991.

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

    USDA-ARS?s Scientific Manuscript database

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

  9. Special Educator Evaluation: Cautions, Concerns and Considerations

    ERIC Educational Resources Information Center

    Semmelroth, Carrie L.; Johnson, Evelyn s.; Allred, Keith W.

    2013-01-01

    There is currently little consensus on how special education teachers should be evaluated in a way that is effective, fair and responsive to their unique teaching responsibilities. In this paper, we explain several of the current approaches to teacher evaluation under consideration, and then provide an overview of the challenges associated with…

  10. Evaluation of cloud-resolving model simulations of midlatitude cirrus with ARM and A-train observations

    DOE PAGES

    Muhlbauer, A.; Ackerman, T. P.; Lawson, R. P.; ...

    2015-07-14

    Cirrus clouds are ubiquitous in the upper troposphere and still constitute one of the largest uncertainties in climate predictions. Our paper evaluates cloud-resolving model (CRM) and cloud system-resolving model (CSRM) simulations of a midlatitude cirrus case with comprehensive observations collected under the auspices of the Atmospheric Radiation Measurements (ARM) program and with spaceborne observations from the National Aeronautics and Space Administration A-train satellites. The CRM simulations are driven with periodic boundary conditions and ARM forcing data, whereas the CSRM simulations are driven by the ERA-Interim product. Vertical profiles of temperature, relative humidity, and wind speeds are reasonably well simulated bymore » the CSRM and CRM, but there are remaining biases in the temperature, wind speeds, and relative humidity, which can be mitigated through nudging the model simulations toward the observed radiosonde profiles. Simulated vertical velocities are underestimated in all simulations except in the CRM simulations with grid spacings of 500 m or finer, which suggests that turbulent vertical air motions in cirrus clouds need to be parameterized in general circulation models and in CSRM simulations with horizontal grid spacings on the order of 1 km. The simulated ice water content and ice number concentrations agree with the observations in the CSRM but are underestimated in the CRM simulations. The underestimation of ice number concentrations is consistent with the overestimation of radar reflectivity in the CRM simulations and suggests that the model produces too many large ice particles especially toward the cloud base. Simulated cloud profiles are rather insensitive to perturbations in the initial conditions or the dimensionality of the model domain, but the treatment of the forcing data has a considerable effect on the outcome of the model simulations. Despite considerable progress in observations and microphysical parameterizations, simulating the microphysical, macrophysical, and radiative properties of cirrus remains challenging. Comparing model simulations with observations from multiple instruments and observational platforms is important for revealing model deficiencies and for providing rigorous benchmarks. But, there still is considerable need for reducing observational uncertainties and providing better observations especially for relative humidity and for the size distribution and chemical composition of aerosols in the upper troposphere.« less

  11. Regulatory challenges in the review of data from global clinical trials: the PMDA perspective.

    PubMed

    Asano, K; Tanaka, A; Sato, T; Uyama, Y

    2013-08-01

    Regulatory agencies face challenges in reviewing data from global clinical trials (GCTs) in the era of globalization of drug development. One major challenge is consideration of ethnic factors in evaluating GCT data so as to extrapolate foreign population data to one's own national population. Here, we present the Pharmaceuticals and Medical Devices Agency (PMDA) perspective in reviewing GCT data in new drug applications (NDAs) and discuss future challenges for new drug approval.

  12. A systematic literature review of the key challenges for developing the structure of public health economic models.

    PubMed

    Squires, Hazel; Chilcott, James; Akehurst, Ronald; Burr, Jennifer; Kelly, Michael P

    2016-04-01

    To identify the key methodological challenges for public health economic modelling and set an agenda for future research. An iterative literature search identified papers describing methodological challenges for developing the structure of public health economic models. Additional multidisciplinary literature searches helped expand upon important ideas raised within the review. Fifteen articles were identified within the formal literature search, highlighting three key challenges: inclusion of non-healthcare costs and outcomes; inclusion of equity; and modelling complex systems and multi-component interventions. Based upon these and multidisciplinary searches about dynamic complexity, the social determinants of health, and models of human behaviour, six areas for future research were specified. Future research should focus on: the use of systems approaches within health economic modelling; approaches to assist the systematic consideration of the social determinants of health; methods for incorporating models of behaviour and social interactions; consideration of equity; and methodology to help modellers develop valid, credible and transparent public health economic model structures.

  13. 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.

  14. Assessing the cumulative environmental effects of marine renewable energy developments: Establishing common ground.

    PubMed

    Willsteed, Edward; Gill, Andrew B; Birchenough, Silvana N R; Jude, Simon

    2017-01-15

    Assessing and managing the cumulative impacts of human activities on the environment remains a major challenge to sustainable development. This challenge is highlighted by the worldwide expansion of marine renewable energy developments (MREDs) in areas already subject to multiple activities and climate change. Cumulative effects assessments in theory provide decision makers with adequate information about how the environment will respond to the incremental effects of licensed activities and are a legal requirement in many nations. In practise, however, such assessments are beset by uncertainties resulting in substantial delays during the licensing process that reduce MRED investor confidence and limit progress towards meeting climate change targets. In light of these targets and ambitions to manage the marine environment sustainably, reducing the uncertainty surrounding MRED effects and cumulative effects assessment are timely and vital. This review investigates the origins and evolution of cumulative effects assessment to identify why the multitude of approaches and pertinent research have emerged, and discusses key considerations and challenges relevant to assessing the cumulative effects of MREDs and other activities on ecosystems. The review recommends a shift away from the current reliance on disparate environmental impact assessments and limited strategic environmental assessments, and a move towards establishing a common system of coordinated data and research relative to ecologically meaningful areas, focussed on the needs of decision makers tasked with protecting and conserving marine ecosystems and services. Copyright © 2016. Published by Elsevier B.V.

  15. Iterative near-term ecological forecasting: Needs, opportunities, and challenges

    USGS Publications Warehouse

    Dietze, Michael C.; Fox, Andrew; Beck-Johnson, Lindsay; Betancourt, Julio L.; Hooten, Mevin B.; Jarnevich, Catherine S.; Keitt, Timothy H.; Kenney, Melissa A.; Laney, Christine M.; Larsen, Laurel G.; Loescher, Henry W.; Lunch, Claire K.; Pijanowski, Bryan; Randerson, James T.; Read, Emily; Tredennick, Andrew T.; Vargas, Rodrigo; Weathers, Kathleen C.; White, Ethan P.

    2018-01-01

    Two foundational questions about sustainability are “How are ecosystems and the services they provide going to change in the future?” and “How do human decisions affect these trajectories?” Answering these questions requires an ability to forecast ecological processes. Unfortunately, most ecological forecasts focus on centennial-scale climate responses, therefore neither meeting the needs of near-term (daily to decadal) environmental decision-making nor allowing comparison of specific, quantitative predictions to new observational data, one of the strongest tests of scientific theory. Near-term forecasts provide the opportunity to iteratively cycle between performing analyses and updating predictions in light of new evidence. This iterative process of gaining feedback, building experience, and correcting models and methods is critical for improving forecasts. Iterative, near-term forecasting will accelerate ecological research, make it more relevant to society, and inform sustainable decision-making under high uncertainty and adaptive management. Here, we identify the immediate scientific and societal needs, opportunities, and challenges for iterative near-term ecological forecasting. Over the past decade, data volume, variety, and accessibility have greatly increased, but challenges remain in interoperability, latency, and uncertainty quantification. Similarly, ecologists have made considerable advances in applying computational, informatic, and statistical methods, but opportunities exist for improving forecast-specific theory, methods, and cyberinfrastructure. Effective forecasting will also require changes in scientific training, culture, and institutions. The need to start forecasting is now; the time for making ecology more predictive is here, and learning by doing is the fastest route to drive the science forward.

  16. Iterative near-term ecological forecasting: Needs, opportunities, and challenges.

    PubMed

    Dietze, Michael C; Fox, Andrew; Beck-Johnson, Lindsay M; Betancourt, Julio L; Hooten, Mevin B; Jarnevich, Catherine S; Keitt, Timothy H; Kenney, Melissa A; Laney, Christine M; Larsen, Laurel G; Loescher, Henry W; Lunch, Claire K; Pijanowski, Bryan C; Randerson, James T; Read, Emily K; Tredennick, Andrew T; Vargas, Rodrigo; Weathers, Kathleen C; White, Ethan P

    2018-02-13

    Two foundational questions about sustainability are "How are ecosystems and the services they provide going to change in the future?" and "How do human decisions affect these trajectories?" Answering these questions requires an ability to forecast ecological processes. Unfortunately, most ecological forecasts focus on centennial-scale climate responses, therefore neither meeting the needs of near-term (daily to decadal) environmental decision-making nor allowing comparison of specific, quantitative predictions to new observational data, one of the strongest tests of scientific theory. Near-term forecasts provide the opportunity to iteratively cycle between performing analyses and updating predictions in light of new evidence. This iterative process of gaining feedback, building experience, and correcting models and methods is critical for improving forecasts. Iterative, near-term forecasting will accelerate ecological research, make it more relevant to society, and inform sustainable decision-making under high uncertainty and adaptive management. Here, we identify the immediate scientific and societal needs, opportunities, and challenges for iterative near-term ecological forecasting. Over the past decade, data volume, variety, and accessibility have greatly increased, but challenges remain in interoperability, latency, and uncertainty quantification. Similarly, ecologists have made considerable advances in applying computational, informatic, and statistical methods, but opportunities exist for improving forecast-specific theory, methods, and cyberinfrastructure. Effective forecasting will also require changes in scientific training, culture, and institutions. The need to start forecasting is now; the time for making ecology more predictive is here, and learning by doing is the fastest route to drive the science forward.

  17. Challenges for malaria elimination in Brazil.

    PubMed

    Ferreira, Marcelo U; Castro, Marcia C

    2016-05-20

    Brazil currently contributes 42 % of all malaria cases reported in the Latin America and the Caribbean, a region where major progress towards malaria elimination has been achieved in recent years. In 2014, malaria burden in Brazil (143,910 microscopically confirmed cases and 41 malaria-related deaths) has reached its lowest levels in 35 years, Plasmodium falciparum is highly focal, and the geographic boundary of transmission has considerably shrunk. Transmission in Brazil remains entrenched in the Amazon Basin, which accounts for 99.5 % of the country's malaria burden. This paper reviews major lessons learned from past and current malaria control policies in Brazil. A comprehensive discussion of the scientific and logistic challenges that may impact malaria elimination efforts in the country is presented in light of the launching of the Plan for Elimination of Malaria in Brazil in November 2015. Challenges for malaria elimination addressed include the high prevalence of symptomless and submicroscopic infections, emerging anti-malarial drug resistance in P. falciparum and Plasmodium vivax and the lack of safe anti-relapse drugs, the largely neglected burden of malaria in pregnancy, the need for better vector control strategies where Anopheles mosquitoes present a highly variable biting behaviour, human movement, the need for effective surveillance and tools to identify foci of infection in areas with low transmission, and the effects of environmental changes and climatic variability in transmission. Control actions launched in Brazil and results to come are likely to influence control programs in other countries in the Americas.

  18. Improving our legacy: Incorporation of adaptive management into state wildlife action plans

    USGS Publications Warehouse

    Fontaine, J.J.

    2011-01-01

    The loss of biodiversity is a mounting concern, but despite numerous attempts there are few large scale conservation efforts that have proven successful in reversing current declines. Given the challenge of biodiversity conservation, there is a need to develop strategic conservation plans that address species declines even with the inherent uncertainty in managing multiple species in complex environments. In 2002, the State Wildlife Grant program was initiated to fulfill this need, and while not explicitly outlined by Congress follows the fundamental premise of adaptive management, 'Learning by doing'. When action is necessary, but basic biological information and an understanding of appropriate management strategies are lacking, adaptive management enables managers to be proactive in spite of uncertainty. However, regardless of the strengths of adaptive management, the development of an effective adaptive management framework is challenging. In a review of 53 State Wildlife Action Plans, I found a keen awareness by planners that adaptive management was an effective method for addressing biodiversity conservation, but the development and incorporation of explicit adaptive management approaches within each plan remained elusive. Only ???25% of the plans included a framework for how adaptive management would be implemented at the project level within their state. There was, however, considerable support across plans for further development and implementation of adaptive management. By furthering the incorporation of adaptive management principles in conservation plans and explicitly outlining the decision making process, states will be poised to meet the pending challenges to biodiversity conservation. ?? 2010 .

  19. Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration.

    PubMed

    Mauck, Robert L; Baker, Brendon M; Nerurkar, Nandan L; Burdick, Jason A; Li, Wan-Ju; Tuan, Rocky S; Elliott, Dawn M

    2009-06-01

    Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures. Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix. When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury. To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies. These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues. This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation. This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function. Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs. We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation.

  20. Engineering on the Straight and Narrow: The Mechanics of Nanofibrous Assemblies for Fiber-Reinforced Tissue Regeneration

    PubMed Central

    Baker, Brendon M.; Nerurkar, Nandan L.; Burdick, Jason A.; Li, Wan-Ju; Tuan, Rocky S.; Elliott, Dawn M.

    2009-01-01

    Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures. Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix. When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury. To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies. These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues. This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation. This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function. Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs. We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation. PMID:19207040

  1. Improving our legacy: incorporation of adaptive management into state wildlife action plans.

    PubMed

    Fontaine, Joseph J

    2011-05-01

    The loss of biodiversity is a mounting concern, but despite numerous attempts there are few large scale conservation efforts that have proven successful in reversing current declines. Given the challenge of biodiversity conservation, there is a need to develop strategic conservation plans that address species declines even with the inherent uncertainty in managing multiple species in complex environments. In 2002, the State Wildlife Grant program was initiated to fulfill this need, and while not explicitly outlined by Congress follows the fundamental premise of adaptive management, 'Learning by doing'. When action is necessary, but basic biological information and an understanding of appropriate management strategies are lacking, adaptive management enables managers to be proactive in spite of uncertainty. However, regardless of the strengths of adaptive management, the development of an effective adaptive management framework is challenging. In a review of 53 State Wildlife Action Plans, I found a keen awareness by planners that adaptive management was an effective method for addressing biodiversity conservation, but the development and incorporation of explicit adaptive management approaches within each plan remained elusive. Only ~25% of the plans included a framework for how adaptive management would be implemented at the project level within their state. There was, however, considerable support across plans for further development and implementation of adaptive management. By furthering the incorporation of adaptive management principles in conservation plans and explicitly outlining the decision making process, states will be poised to meet the pending challenges to biodiversity conservation. Published by Elsevier Ltd.

  2. MO-E-BRC-00: Online Adaptive Radiotherapy - Considerations for Practical Clinical Implementation

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

    NONE

    Online adaptive radiation therapy has the potential to ensure delivery of optimal treatment to the patient by accounting for anatomical and potentially functional changes that occur from one fraction to the next and over the course of treatment. While on-line adaptive RT (ART) has been a topic of many publications, discussions, and research, it has until very recently remained largely a concept and not a practical implementation. However, recent advances in on-table imaging, use of deformable image registration for contour generation and dose tracking, faster and more efficient plan optimization, as well as fast quality assurance method has enabled themore » implementation of ART in the clinic in the past couple of years. The introduction of these tools into routine clinical use requires many considerations and progressive knowledge to understand how processes that have historically taken hours/days to complete can now be done in less than 30 minutes. This session will discuss considerations to perform real time contouring, planning and patient specific QA, as well as a practical workflow and the required resources. Learning Objectives: To understand the difficulties, challenges and available technologies for online adaptive RT. To understand how to implement online adaptive therapy in a clinical environment and to understand the workflow and resources required. To understand the limitations and sources of uncertainty in the online adaptive process I have research funding from ViewRay Inc. and Philips Medical Systems.; R. Kashani, I have research funding from ViewRay Inc. and Philips Medical Systems.; X. Li, Research supported by Elekta Inc.« less

  3. The natural course of anxiety disorders in the elderly: a systematic review of longitudinal trials.

    PubMed

    Sami, Musa Basseer; Nilforooshan, Ramin

    2015-07-01

    The anxiety disorders are a prevalent mental health problem in older age with a considerable impact on quality of life. Until recently there have been few longitudinal studies on anxiety in this age group, consequently most of the evidence to date has been cross-sectional in nature. We undertook a literature search of Medline, PsycINFO, the Cochrane trials database and the TRIP medical database to identify longitudinal studies which would help elucidate natural history and prognosis of anxiety disorders in the elderly. We identified 12 papers of 10 longitudinal studies in our Review. This represented 34,691 older age participants with 5,199 with anxiety disorders including anxious depression and 3,532 individuals with depression without anxiety. Relapse rates of anxiety disorders are high over 6 year follow-up with considerable migration to mixed anxiety-depression and pure depressive mood episodes. Mixed anxiety-depression appears to be a poorer prognostic state than pure anxiety or pure depression with higher relapse rates across studies. In community settings treatment rates are low with 7-44% of the anxious elderly treated on antidepressant medications. To our knowledge this is the first Systematic Review of longitudinal trials of anxiety disorders in older people. Major longitudinal studies of the anxious elderly are establishing the high risk of relapse and persistence alongside the progression to depression and anxiety depression states. There remains considerable under-treatment in community studies. Specialist assessment and treatment and major public health awareness of the challenges of anxiety disorders in the elderly are required.

  4. Regulatory perspective on remaining challenges for utilization of pharmacogenomics-guided drug developments.

    PubMed

    Otsubo, Yasuto; Ishiguro, Akihiro; Uyama, Yoshiaki

    2013-01-01

    Pharmacogenomics-guided drug development has been implemented in practice in the last decade, resulting in increased labeling of drugs with pharmacogenomic information. However, there are still many challenges remaining in utilizing this process. Here, we describe such remaining challenges from the regulatory perspective, specifically focusing on sample collection, biomarker qualification, ethnic factors, codevelopment of companion diagnostics and means to provide drugs for off-target patients. To improve the situation, it is important to strengthen international harmonization and collaboration among academia, industries and regulatory agencies, followed by the establishment of an international guideline on this topic. Communication with a regulatory agency from an early stage of drug development is also a key to success.

  5. 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

  6. Minnesota 4-H Science of Agriculture Challenge: Infusing Agricultural Science and Engineering Concepts into 4-H Youth Development

    ERIC Educational Resources Information Center

    Rice, Joshua E.; Rugg, Bradley; Davis, Sharon

    2016-01-01

    Youth involved in 4-H projects have been engaged in science-related endeavors for years. Since 2006, 4-H has invested considerable resources in the advancement of science learning. The new Minnesota 4-H Science of Agriculture Challenge program challenges 4-H youth to work together to identify agriculture-related issues in their communities and to…

  7. The Proposed MACRA/MIPS Threshold for Patient-Facing Encounters: What It Means for Radiologists.

    PubMed

    Rosenkrantz, Andrew B; Hirsch, Joshua A; Allen, Bibb; Wang, Wenyi; Hughes, Danny R; Nicola, Gregory N

    2017-03-01

    In implementing the Merit-Based Incentive Payment System (MIPS), CMS will provide special considerations to physicians with infrequent face-to-face patient encounters by reweighting MIPS performance categories to account for the unique circumstances facing these providers. The aim of this study was to determine the impact of varying criteria on the fraction of radiologists who are likely to receive special considerations for performance assessment under MIPS. Data from the 2014 Medicare Physician and Other Supplier file for 28,710 diagnostic radiologists were used to determine the fraction of radiologists meeting various proposed criteria for receiving special considerations. For each definition, the fraction of patient-facing encounters among all billed codes was determined for those radiologists not receiving special considerations. When using the criterion proposed by CMS that physicians will receive special considerations if billing ≤25 evaluation and management services or surgical codes, 72.0% of diagnostic radiologists would receive special considerations, though such encounters would represent only 2.1% of billed codes among remaining diagnostic radiologists without special considerations. If CMS were to apply an alternative criterion of billing ≤100 evaluation and management codes exclusively, 98.8% of diagnostic radiologists would receive special considerations. At this threshold, patient-facing encounters would represent approximately 10% of billed codes among remaining radiologists without special considerations. The current CMS proposed criterion for special considerations would result in a considerable fraction of radiologists being evaluated on the basis of measures that are not reflective of their practice and beyond their direct control. Alternative criteria could help ensure that radiologists are provided a fair opportunity for success in performance review under the MIPS. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  8. Bats on a Budget: Torpor-Assisted Migration Saves Time and Energy

    PubMed Central

    McGuire, Liam P.; Jonasson, Kristin A.; Guglielmo, Christopher G.

    2014-01-01

    Bats and birds must balance time and energy budgets during migration. Migrating bats face similar physiological challenges to birds, but nocturnality creates special challenges for bats, such as a conflict between travelling and refueling, which many birds avoid by feeding in daylight and flying at night. As endothermic animals, bats and birds alike must expend substantial amounts of energy to maintain high body temperatures. For migratory birds refueling at stopovers, remaining euthermic during inactive periods reduces the net refuelling rate, thereby prolonging stopover duration and delaying subsequent movement. We hypothesized that bats could mitigate similar ambient-temperature dependent costs by using a torpor-assisted migration strategy. We studied silver-haired bats Lasionycteris noctivagans during autumn migration using a combination of respirometry and temperature-sensitive radiotelemetry to estimate energy costs incurred under ambient temperature conditions, and the energy that bats saved by using torpor during daytime roosting periods. All bats, regardless of sex, age, or body condition used torpor at stopover and saved up to 91% of the energy they would have expended to remain euthermic. Furthermore, bats modulated use of torpor depending on ambient temperature. By adjusting the time spent torpid, bats achieved a rate of energy expenditure independent of the ambient temperature encountered at stopover. By lowering body temperature during inactive periods, fuel stores are spared, reducing the need for refuelling. Optimal migration models consider trade-offs between time and energy. Heterothermy provides a physiological strategy that allows bats to conserve energy without paying a time penalty as they migrate. Although uncommon, some avian lineages are known to use heterothermy, and current theoretical models of migration may not be appropriate for these groups. We propose that thermoregulatory strategies should be an important consideration of future migration studies of both bats and birds. PMID:25551615

  9. Role of the 85-Kilobase Plasmid and Plasmid-Encoded Virulence-Associated Protein A in Intracellular Survival and Virulence of Rhodococcus equi

    PubMed Central

    Giguère, Steeve; Hondalus, Mary K.; Yager, Julie A.; Darrah, Patricia; Mosser, David M.; Prescott, John F.

    1999-01-01

    Rhodococcus equi is a facultative intracellular pathogen of macrophages and a cause of pneumonia in young horses (foals) and immunocompromised people. Isolates of R. equi from pneumonic foals typically contain large, 85- or 90-kb plasmids encoding a highly immunogenic virulence-associated protein (VapA). The objective of this study was to determine the role of the 85-kb plasmid and VapA in the intracellular survival and virulence of R. equi. Clinical isolates containing the plasmid and expressing VapA efficiently replicated within mouse macrophages in vitro, while plasmid-cured derivatives of these organisms did not multiply intracellularly. An isolate harboring the large plasmid also replicated in the tissues of experimentally infected mice, whereas its plasmid-cured derivative was rapidly cleared. All foals experimentally infected with a plasmid-containing clinical isolate developed severe bronchopneumonia, whereas the foals infected with its plasmid-cured derivative remained asymptomatic and free of visible lung lesions. By day 14 postinfection, lung bacterial burdens had increased considerably in foals challenged with the plasmid-containing clinical isolate. In contrast, bacteria could no longer be cultured from the lungs of foals challenged with the isogenic plasmid-cured derivative. A recombinant, plasmid-cured derivative expressing wild-type levels of VapA failed to replicate in macrophages and remained avirulent for both mice and foals. These results show that the 85-kb plasmid of R. equi is essential for intracellular replication within macrophages and for development of disease in the native host, the foal. However, expression of VapA alone is not sufficient to restore the virulence phenotype. PMID:10377138

  10. A window into the future of the Earth, hidden in the jungles of Costa Rica's volcanoes

    NASA Astrophysics Data System (ADS)

    Fisher, J. B.; Schwandner, F. M.; Asner, G. P.; Schimel, D.; Norby, R. J.; Keller, M.; Pavlick, R.; Braverman, A. J.; Pieri, D. C.; Diaz, J. A.; Gutierrez, M.; Duarte, E. A.; Lewicki, J. L.; Manning, C. E.; Deering, C. D.; Seibt, U.; Miller, G. R.; Drewry, D.; Chambers, J.

    2017-12-01

    The CO2 fertilization response of the terrestrial biosphere contributes among the largest sensitivities and uncertainties across projections of the Earth's future. The source of that uncertainty can be pinpointed to the largest fluxes in the biosphere: the tropics. Free Air CO2 Enrichment (FACE) experiments have contributed immensely to our understanding of short-term CO2 fertilization, but, outside of a small pilot study in development, have been absent in the tropics. This is largely due to numerous hurdles of not only conducting such experiments in challenging environments, but also due to the need to expand their extent considerably to encompass the enormous diversity of species-level responses, in addition to the need for multi-decadal scale responses. As such, we have remained at a critical impasse in our ability to advance understanding of the response of the tropical biosphere to increasing CO2. Recent discoveries have found a cluster of volcanoes degassing CO2 into tropical ecosystems in Costa Rica at concentrations similar to future Earth atmosphere levels. The degassing has been occurring persistently from 10s to 100s of years over 10s to 100s of square kilometers, at different levels depending on the volcano. Fortuitously, this provides a natural "experiment" across a range of conditions needed to assess a widespread and long-lived tropical ecosystem response to elevated CO2: tree species will have had time to shift in composition, traits, structure, and function. Nonetheless, due both to the challenges with assessing these changes on the ground, and heterogeneity causing problems with coarse-scale satellite remote sensing observations, this "window" into the future of the Earth has remained veiled. Here, we describe an airborne-based plan designed to uncover this gem hidden in the jungles of Costa Rica's volcanoes.

  11. 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.

  12. Online Learner Engagement: Opportunities and Challenges with Using Data Analytics

    ERIC Educational Resources Information Center

    Bodily, Robert; Graham, Charles R.; Bush, Michael D.

    2017-01-01

    This article describes the crossroads between learning analytics and learner engagement. The authors do this by describing specific challenges of using analytics to support student engagement from three distinct perspectives: pedagogical considerations, technological issues, and interface design concerns. While engaging online learners presents a…

  13. The palm oil supply chain, deforestation and peat clearing

    NASA Astrophysics Data System (ADS)

    Boucher, D. H.

    2013-12-01

    The palm oil industry has expanded rapidly in the last two decades, particularly in Indonesia. A considerable amount of this expansion has been at the expense of forests and peatlands, resulting in considerable greenhouse gas emissions. Now the industry is faced with two new challenges. There is a possible oversupply on the global market due to recent expansion and the time lag between clearing and new production coming on line, which may depress prices considerably. Furthermore, there is increasing pressure to reduce the industry's impact on climate and biodiversity, exemplified by the commitment by the businesses of the Consumer Goods Forum to eliminate deforestation from their supply chains by 2020. This presentation will examine the interaction between these two challenges and its implications for the industry, in both southeast Asia and new regions of expansion, and how this interaction could transform the industry's mode of expansion in the coming decade.

  14. Institutional design and organizational practice for universal coverage in lesser-developed countries: challenges facing the Lao PDR.

    PubMed

    Ahmed, Shakil; Annear, Peter Leslie; Phonvisay, Bouaphat; Phommavong, Chansaly; Cruz, Valeria de Oliveira; Hammerich, Asmus; Jacobs, Bart

    2013-11-01

    There is now widespread acceptance of the universal coverage approach, presented in the 2010 World Health Report. There are more and more voices for the benefit of creating a single national risk pool. Now, a body of literature is emerging on institutional design and organizational practice for universal coverage, related to management of the three health-financing functions: collection, pooling and purchasing. While all countries can move towards universal coverage, lower-income countries face particular challenges, including scarce resources and limited capacity. Recently, the Lao PDR has been preparing options for moving to a single national health insurance scheme. The aim is to combine four different social health protection schemes into a national health insurance authority (NHIA) with a single national fund- and risk-pool. This paper investigates the main institutional and organizational challenges related to the creation of the NHIA. The paper uses a qualitative approach, drawing on the World Health Organization's institutional and Organizational Assessment for Improving and Strengthening health financing (OASIS) conceptual framework for data analysis. Data were collected from a review of key health financing policy documents and from 17 semi-structured key informant interviews. Policy makers and advisors are confronting issues related to institutional arrangements, funding sources for the authority and government support for subsidies to the demand-side health financing schemes. Compulsory membership is proposed, but the means for covering the informal sector have not been resolved. While unification of existing schemes may be the basis for creating a single risk pool, challenges related to administrative capacity and cross-subsidies remain. The example of Lao PDR illustrates the need to include consideration of national context, the sequencing of reforms and the time-scale appropriate for achieving universal coverage. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. The challenges and opportunities of translating best practice immunisation strategies among low performing general practices to reduce equity gaps in childhood immunisation coverage in New Zealand.

    PubMed

    Turner, Nikki M; Charania, Nadia A; Chong, Angela; Stewart, Joanna; Taylor, Lynn

    2017-01-01

    Immunisation coverage rates vary considerably at the local level across New Zealand and challenges remain with effectively translating best available research evidence into public health practice. This study aimed to translate best practices from high performing general practices into strategies to improve childhood immunisation coverage among low performing practices. An intervention study was undertaken of general practices with low immunisation coverage rates and a high percentage of the enrolled population being of Māori ethnicity. Intervention groups received customised action plans and support for a 12 month period while control groups received 'business as usual' support. Structured interviews were conducted with key informants from all participating practices to understand current aspects related to childhood immunisation delivery and surveys were conducted to understand how the intervention worked. Collected data were thematically analysed. Ten sites were randomised to either intervention ( n  = 6) or control group ( n  = 4). Positive aspects of childhood immunisation delivery included high prioritisation at the practice and staff being pro-immunisation and knowledgeable. Key challenges experienced included inaccurate family contact information and discrepancies with referral processes to other providers. Other challenges noted were building rapport with families and vaccine hesitancy. The action plans included various strategies aimed to improve processes at the practice, contact and engagement with parents, and partnership development with local service providers. Creating customised action plans and providing support to providers were considered as helpful approaches when attempting to improve childhood immunisation coverage rates. Our study supports the notion that one strategy will not solely by itself improve childhood immunisation rates and highlights the importance of having a toolkit of strategies from which to draw from.

  16. Introversion and medical student education: challenges for both students and educators.

    PubMed

    Davidson, Bernard; Gillies, Ralph A; Pelletier, Allen L

    2015-01-01

    Introversion is one of the personality factors that has been shown to be associated with performance in medical school. Prior cross-sectional studies highlight performance evaluation differences between introverted and extraverted medical students, though the mechanisms and implications of these differences remain relatively unexplained and understudied. This gap in the literature has become more salient as medical schools are employing more interactive learning strategies into their curricula which may disproportionately challenge introverted learners. In this article, we provide an overview and working definition of introversion as a valid construct occurring on a continuum. We apply a goodness of fit model to explore how various medical training contexts may be more or less challenging for introverted students and the potential consequences of a poor fit. As preliminary support for these hypothesized challenges, we share observations from students self-identified as introverts. Examples include introverted students feeling at times like misfits, questioning a need to change their identity to succeed in medical school, and being judged as underperformers. We offer pragmatic suggestions for improving the fit between introverted students and their training contexts, such as teachers and students pausing between a question being asked and the initial response being offered and teachers differentiating between anxious and introverted behaviors. We conclude with suggested areas for future qualitative and quantitative research to examine how medical school curricula and the teaching environment may be differentially impacting the learning and health of introverted and extraverted students. Extraverted behaviors will continue to be an important part of medical training and practice, but the merits of introverted behaviors warrant further consideration as both medical training and practice evolve. Educators who make manageable adjustments to current teaching practices can improve the learning for both introverted and extraverted styles of academic engagement.

  17. The Challenge of Timely, Responsive and Rigorous Ethics Review of Disaster Research: Views of Research Ethics Committee Members.

    PubMed

    Hunt, Matthew; Tansey, Catherine M; Anderson, James; Boulanger, Renaud F; Eckenwiler, Lisa; Pringle, John; Schwartz, Lisa

    2016-01-01

    Research conducted following natural disasters such as earthquakes, floods or hurricanes is crucial for improving relief interventions. Such research, however, poses ethical, methodological and logistical challenges for researchers. Oversight of disaster research also poses challenges for research ethics committees (RECs), in part due to the rapid turnaround needed to initiate research after a disaster. Currently, there is limited knowledge available about how RECs respond to and appraise disaster research. To address this knowledge gap, we investigated the experiences of REC members who had reviewed disaster research conducted in low- or middle-income countries. We used interpretive description methodology and conducted in-depth interviews with 15 respondents. Respondents were chairs, members, advisors, or coordinators from 13 RECs, including RECs affiliated with universities, governments, international organizations, a for-profit REC, and an ad hoc committee established during a disaster. Interviews were analyzed inductively using constant comparative techniques. Through this process, three elements were identified as characterizing effective and high-quality review: timeliness, responsiveness and rigorousness. To ensure timeliness, many RECs rely on adaptations of review procedures for urgent protocols. Respondents emphasized that responsive review requires awareness of and sensitivity to the particularities of disaster settings and disaster research. Rigorous review was linked with providing careful assessment of ethical considerations related to the research, as well as ensuring independence of the review process. Both the frequency of disasters and the conduct of disaster research are on the rise. Ensuring effective and high quality review of disaster research is crucial, yet challenges, including time pressures for urgent protocols, exist for achieving this goal. Adapting standard REC procedures may be necessary. However, steps should be taken to ensure that ethics review of disaster research remains diligent and thorough.

  18. The Challenge of Timely, Responsive and Rigorous Ethics Review of Disaster Research: Views of Research Ethics Committee Members

    PubMed Central

    Hunt, Matthew; Tansey, Catherine M.

    2016-01-01

    Background Research conducted following natural disasters such as earthquakes, floods or hurricanes is crucial for improving relief interventions. Such research, however, poses ethical, methodological and logistical challenges for researchers. Oversight of disaster research also poses challenges for research ethics committees (RECs), in part due to the rapid turnaround needed to initiate research after a disaster. Currently, there is limited knowledge available about how RECs respond to and appraise disaster research. To address this knowledge gap, we investigated the experiences of REC members who had reviewed disaster research conducted in low- or middle-income countries. Methods We used interpretive description methodology and conducted in-depth interviews with 15 respondents. Respondents were chairs, members, advisors, or coordinators from 13 RECs, including RECs affiliated with universities, governments, international organizations, a for-profit REC, and an ad hoc committee established during a disaster. Interviews were analyzed inductively using constant comparative techniques. Results Through this process, three elements were identified as characterizing effective and high-quality review: timeliness, responsiveness and rigorousness. To ensure timeliness, many RECs rely on adaptations of review procedures for urgent protocols. Respondents emphasized that responsive review requires awareness of and sensitivity to the particularities of disaster settings and disaster research. Rigorous review was linked with providing careful assessment of ethical considerations related to the research, as well as ensuring independence of the review process. Conclusion Both the frequency of disasters and the conduct of disaster research are on the rise. Ensuring effective and high quality review of disaster research is crucial, yet challenges, including time pressures for urgent protocols, exist for achieving this goal. Adapting standard REC procedures may be necessary. However, steps should be taken to ensure that ethics review of disaster research remains diligent and thorough. PMID:27327165

  19. The ClearEarth Project: Preliminary Findings from Experiments in Applying the CLEARTK NLP Pipeline and Annotation Tools Developed for Biomedicine to the Earth Sciences

    NASA Astrophysics Data System (ADS)

    Duerr, R.; Thessen, A.; Jenkins, C. J.; Palmer, M.; Myers, S.; Ramdeen, S.

    2016-12-01

    The ability to quickly find, easily use and effortlessly integrate data from a variety of sources is a grand challenge in Earth sciences, one around which entire research programs have been built. A myriad of approaches to tackling components of this challenge have been demonstrated, often with some success. Yet finding, assessing, accessing, using and integrating data remains a major challenge for many researchers. A technology that has shown promise in nearly every aspect of the challenge is semantics. Semantics has been shown to improve data discovery, facilitate assessment of a data set, and through adoption of the W3C's Linked Data Platform to have improved data integration and use at least for data amenable to that paradigm. Yet the creation of semantic resources has been slow. Why? Amongst a plethora of other reasons, it is because semantic expertise is rare in the Earth and Space sciences; the creation of semantic resources for even a single discipline is labor intensive and requires agreement within the discipline; best practices, methods and tools for supporting the creation and maintenance of the resources generated are in flux; and the human and financial capital needed are rarely available in the Earth sciences. However, other fields, such as biomedicine, have made considerable progress in these areas. The NSF-funded ClearEarth project is adapting the methods and tools from these communities for the Earth sciences in the expectation that doing so will enhance progress and the rate at which the needed semantic resources are created. We discuss progress and results to date, lessons learned from this adaptation process, and describe our upcoming efforts to extend this knowledge to the next generation of Earth and data scientists.

  20. The ethics of research using electronic mail discussion groups.

    PubMed

    Kralik, Debbie; Warren, Jim; Price, Kay; Koch, Tina; Pignone, Gino

    2005-12-01

    The aim of this paper is to identify and discuss the ethical considerations that have confronted and challenged the research team when researchers facilitate conversations using private electronic mail discussion lists. The use of electronic mail group conversations, as a collaborative data generation method, remains underdeveloped in nursing. Ethical challenges associated with this approach to data generation have only begun to be considered. As receipt of ethics approval for a study titled; 'Describing transition with people who live with chronic illness' we have been challenged by many ethical dilemmas, hence we believe it is timely to share the issues that have confronted the research team. These discussions are essential so we can understand the possibilities for research interaction, communication, and collaboration made possible by advanced information technologies. Our experiences in this study have increased our awareness for ongoing ethical discussions about privacy, confidentiality, consent, accountability and openness underpinning research with human participants when generating data using an electronic mail discussion group. We describe how we work at upholding these ethical principles focusing on informed consent, participant confidentiality and privacy, the participants as threats to themselves and one another, public-private confusion, employees with access, hackers and threats from the researchers. A variety of complex issues arise during cyberspace research that can make the application of traditional ethical standards troublesome. Communication in cyberspace alters the temporal, spatial and sensory components of human interaction, thereby challenging traditional ethical definitions and calling to question some basic assumptions about identity and ones right to keep aspects of it confidential. Nurse researchers are bound by human research ethics protocols; however, the nature of research by electronic mail generates moral issues as well as ethical concerns. Vigilance by researchers is required to ensure that data are viewed within the scope of the enabling ethics approval.

  1. Scale considerations for ecosystem management

    Treesearch

    Jonathan B. Haufler; Thomas R. Crow; David Wilcove

    1999-01-01

    One of the difficult challenges facing ecosystem management is the determination of appropriate spatial and temporal scales to use. Scale in spatial sence includes considerations of both the size area or extent of an ecosystem management activity, as well as thedegree of resolution of mapped or measured data. In the temporal sense, scale concerns the duration of both...

  2. Integrating climate change considerations into forest management tools and training

    Treesearch

    Linda M. Nagel; Christopher W. Swanston; Maria K. Janowiak

    2010-01-01

    Silviculturists are currently facing the challenge of developing management strategies that meet broad ecological and social considerations in spite of a high degree of uncertainty in future climatic conditions. Forest managers need state-of-the-art knowledge about climate change and potential impacts to facilitate development of silvicultural objectives and...

  3. Decision Points and Considerations for Identifying Rural Districts That Have Closed Student Achievement Gaps. REL 2016-130

    ERIC Educational Resources Information Center

    Culbertson, Michael J.; Billig, Shelley H.

    2016-01-01

    Rural districts have long faced challenges in closing achievement gaps between subgroups of students. This brief report describes key decision points and considerations for decision-makers interested in identifying rural districts that have closed academic achievement gaps. Examining practices in these districts may suggest activities associated…

  4. A Visual Haptic System for Children with Learning Disabilities: Software and Hardware Design Considerations

    ERIC Educational Resources Information Center

    Subrahmaniyan, Neeraja; Krishnaswamy, Swetha; Chowriappa, Ashirwad; Srimathveeravalli, Govindarajan; Bisantz, Ann; Shriber, Linda; Kesavadas, Thenkurussi

    2012-01-01

    Research has shown that children with learning disabilities exhibit considerable challenges with visual motor integration. While there are specialized Occupational Therapy interventions aimed at visual motor integration, computer games and virtual toys have now become increasingly popular, forming an integral part of children's learning and play.…

  5. Managing Spaces: (Re)working Relations of Strategy and Spatiality in Vocational Education and Training

    ERIC Educational Resources Information Center

    Mulcahy, Dianne

    2007-01-01

    The adoption of a more "open" national training market in vocational education and training (VET) in Australia has led to considerable changes in VET organizations and considerable challenges for VET managers. Recent research has established the critical role that 'strategy' plays in leading and managing these organizations and the…

  6. Counseling Psychology Research on Sexual (Orientation) Minority Issues: Conceptual and Methodological Challenges and Opportunities

    ERIC Educational Resources Information Center

    Moradi, Bonnie; Mohr, Jonathan J.; Worthington, Roger L.; Fassinger, Ruth E.

    2009-01-01

    This lead article of the special issue discusses conceptual and methodological considerations in studying sexual minority issues, particularly in research conducted by counseling psychologists (including the work represented in this special issue). First, the overarching challenge of conceptualizing and defining sexual minority populations is…

  7. The cost of brain diseases: a burden or a challenge?

    PubMed

    DiLuca, Monica; Olesen, Jes

    2014-06-18

    Brain diseases represent a considerable social and economic burden in Europe. With yearly costs of about 800 billion euros and an estimated 179 million people afflicted in 2010, brain diseases are an unquestionable emergency and a grand challenge for neuroscientists. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. 4 CFR 21.5 - Protest issues not for consideration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... official to file a protest or not to file a protest in connection with a public-private competition. [61 FR... business size standards and North American Industry Classification System (NAICS) standards. Challenges of established size standards or the size status of particular firms, and challenges of the selected NAICS code...

  9. 77 FR 2556 - Ethical and Regulatory Challenges in the Development of Pediatric Medical Countermeasures; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-18

    ...] Ethical and Regulatory Challenges in the Development of Pediatric Medical Countermeasures; Public Workshop... Administration (FDA), Office of Pediatric Therapeutics, is announcing a public workshop entitled ``Ethical and... provide a forum for careful consideration of scientific, ethical, and regulatory issues confronting FDA...

  10. MALL: The Pedagogical Challenges

    ERIC Educational Resources Information Center

    Burston, Jack

    2014-01-01

    In this paper the development of mobile-assisted language learning (MALL) over the past 20 years is reviewed with a particular focus on the pedagogical challenges facing its exploitation. Following a consideration of the definition of mobile learning, the paper describes the dominant mobile technologies upon which MALL applications have been…

  11. A Different Way of Viewing History Teaching: Balancing Competing Intellectual Challenges

    ERIC Educational Resources Information Center

    Neumann, Dave

    2010-01-01

    With state content standards always looming in the background, history teachers express concern about "covering the curriculum." And, many history teachers say they have to abandon teaching the "fun stuff" in order to teach state-mandated content. While teaching challenges do entail practical considerations, this article argues…

  12. Counseling Gifted Students: School-Based Considerations and Strategies

    ERIC Educational Resources Information Center

    Kennedy, Kelly; Farley, Jessica

    2018-01-01

    Gifted students are a heterogeneous group, inclusive of those of all cultures, backgrounds, interests, and achievements. Gifted students may not display any more or worse psychological, social, or developmental challenges than their peers, but they also are not immune from these challenges. Moreover, the nature of their giftedness may impact both…

  13. A Consideration of the Challenges Involved in Supervising International Masters Students

    ERIC Educational Resources Information Center

    Brown, Lorraine

    2007-01-01

    This paper explores the challenges facing supervisors of international postgraduate students at the dissertation stage of the masters programme. The central problems of time pressure, language difficulties, a lack of critical analysis and a prevalence of personal problems among international students are discussed. This paper makes recommendations…

  14. Student Mobility: Changing Patterns Challenging Policymakers

    ERIC Educational Resources Information Center

    Pusser, Brian; Turner, Julie Kirsten

    2004-01-01

    Over the past decade, the understanding of student mobility patterns has increased considerably through research based in the analysis of longitudinal data sets. A significant challenge to crafting effective policies on student mobility emerges from most states focusing on full-time, 18-to-24-year-old students. While fewer than half of…

  15. The Big Picture and Specifics of College General Education

    ERIC Educational Resources Information Center

    Gan, Yang

    2018-01-01

    In recent years, general education has developed considerably in Chinese universities, but it still faces many challenges and problems. Among the various negative factors, four problems may be the greatest challenges currently faced by Chinese university general education and ordinary undergraduate education: (1) In the era of massified higher…

  16. Injectable foams for regenerative medicine.

    PubMed

    Prieto, Edna M; Page, Jonathan M; Harmata, Andrew J; Guelcher, Scott A

    2014-01-01

    The design of injectable biomaterials has attracted considerable attention in recent years. Many injectable biomaterials, such as hydrogels and calcium phosphate cements (CPCs), have nanoscale pores that limit the rate of cellular migration and proliferation. While introduction of macroporosity has been suggested to increase cellular infiltration and tissue healing, many conventional methods for generating macropores often require harsh processing conditions that preclude their use in injectable foams. In recent years, processes such as porogen leaching, gas foaming, and emulsion-templating have been adapted to generate macroporosity in injectable CPCs, hydrogels, and hydrophobic polymers. While some of the more mature injectable foam technologies have been evaluated in clinical trials, there are challenges remaining to be addressed, such as the biocompatibility and ultimate fate of the sacrificial phase used to generate pores within the foam after it sets in situ. Furthermore, while implantable scaffolds can be washed extensively to remove undesirable impurities, all of the components required to synthesize injectable foams must be injected into the defect. Thus, every compound in the foam must be biocompatible and noncytotoxic at the concentrations utilized. As future research addresses these critical challenges, injectable macroporous foams are anticipated to have an increasingly significant impact on improving patient outcomes for a number of clinical procedures. © 2013 Wiley Periodicals, Inc.

  17. BIG DATA ANALYTICS AND PRECISION ANIMAL AGRICULTURE SYMPOSIUM: Machine learning and data mining advance predictive big data analysis in precision animal agriculture.

    PubMed

    Morota, Gota; Ventura, Ricardo V; Silva, Fabyano F; Koyama, Masanori; Fernando, Samodha C

    2018-04-14

    Precision animal agriculture is poised to rise to prominence in the livestock enterprise in the domains of management, production, welfare, sustainability, health surveillance, and environmental footprint. Considerable progress has been made in the use of tools to routinely monitor and collect information from animals and farms in a less laborious manner than before. These efforts have enabled the animal sciences to embark on information technology-driven discoveries to improve animal agriculture. However, the growing amount and complexity of data generated by fully automated, high-throughput data recording or phenotyping platforms, including digital images, sensor and sound data, unmanned systems, and information obtained from real-time noninvasive computer vision, pose challenges to the successful implementation of precision animal agriculture. The emerging fields of machine learning and data mining are expected to be instrumental in helping meet the daunting challenges facing global agriculture. Yet, their impact and potential in "big data" analysis have not been adequately appreciated in the animal science community, where this recognition has remained only fragmentary. To address such knowledge gaps, this article outlines a framework for machine learning and data mining and offers a glimpse into how they can be applied to solve pressing problems in animal sciences.

  18. Immunisation registers in Canada: progress made, current situation, and challenges for the future.

    PubMed

    Laroche, J A; Diniz, A J

    2012-04-26

    Immunisation registers have the capacity to capture data on the administration of vaccine doses at the individual level within the population and represent an important tool in assessing immunisation coverage and vaccine uptake. In 1999, the National Advisory Committee on Immunization recommended that a network of immunisation registers be established in Canada. The Canadian Immunization Registry Network (CIRN) was established to coordinate the development of standards and facilitate the sharing of knowledge and experience to develop a national network of such registers. In 2003, the National Immunization Strategy identified immunisation registers as an important component in improving national immunisation surveillance. In addition, there has been consistent public and professional interest in a national immunisation register being available and considerable progress has been made in developing technologies to facilitate the capture of immunisation-related data. More specifically, the automated identification of vaccines, through the use of barcodes on vaccines, will facilitate collection of data related to administered vaccine doses. Nevertheless, challenges remain in the implementation of immunisation registers in all Canadian provinces and territories such that Canada still does not currently have a fully functional network of immunisation registers with the capacity to be interoperable between jurisdictions and to allow for data to be captured at the national level.

  19. The burden of proof: The current state of atrial fibrillation prevention and treatment trials

    PubMed Central

    Zakeri, Rosita; Van Wagoner, David R.; Calkins, Hugh; Wong, Tom; Ross, Heather M.; Heist, E. Kevin; Meyer, Timothy E.; Kowey, Peter R.; Mentz, Robert J.; Cleland, John G.; Pitt, Bertram; Zannad, Faiez; Linde, Cecilia

    2017-01-01

    Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015. PMID:28161513

  20. Technology-delivered adaptations of motivational interviewing for health-related behaviors: A systematic review of the current research

    PubMed Central

    Shingleton, Rebecca M.; Palfai, Tibor P.

    2015-01-01

    Objectives The aims of this paper were to describe and evaluate the methods and efficacy of technology-delivered motivational interviewing interventions (TAMIs), discuss the challenges and opportunities of TAMIs, and provide a framework for future research. Methods We reviewed studies that reported using motivational interviewing (MI) based components delivered via technology and conducted ratings on technology description, comprehensiveness of MI, and study methods. Results The majority of studies were fully-automated and included at least one form of media rich technology to deliver the TAMI. Few studies provided complete descriptions of how MI components were delivered via technology. Of the studies that isolated the TAMI effects, positive changes were reported. Conclusion Researchers have used a range of technologies to deliver TAMIs suggesting feasibility of these methods. However, there are limited data regarding their efficacy, and strategies to deliver relational components remain a challenge. Future research should better characterize the components of TAMIs, empirically test the efficacy of TAMIs with randomized controlled trials, and incorporate fidelity measures. Practice Implications TAMIs are feasible to implement and well accepted. These approaches offer considerable potential to reduce costs, minimize therapist and training burden, and expand the range of clients that may benefit from adaptations of MI. PMID:26298219

  1. Injectable Foams for Regenerative Medicine

    PubMed Central

    Prieto, Edna M.; Page, Jonathan M.; Harmata, Andrew J.

    2013-01-01

    The design of injectable biomaterials has attracted considerable attention in recent years. Many injectable biomaterials, such as hydrogels and calcium phosphate cements, have nanoscale pores that limit the rate of cellular migration and proliferation. While introduction of macroporosity has been suggested to increase cellular infiltration and tissue healing, many conventional methods for generating macropores often require harsh processing conditions that preclude their use in injectable foams. In recent years, processes such as porogen leaching, gas foaming, and emulsion-templating have been adapted to generate macroporosity in injectable calcium phosphate cements, hydrogels, and hydrophobic polymers. While some of the more mature injectable foam technologies have been evaluated in clinical trials, there are challenges remaining to be addressed, such as the biocompatibility and ultimate fate of the sacrificial phase used to generate pores within the foam after it sets in situ. Furthermore, while implantable scaffolds can be washed extensively to remove undesirable impurities, all of the components required to synthesize injectable foams must be injected into the defect. Thus, every compound in the foam must be biocompatible and non-cytotoxic at the concentrations utilized. As future research addresses these critical challenges, injectable macroporous foams are anticipated to have an increasingly significant impact on improving patient outcomes for a number of clinical procedures. PMID:24127230

  2. Predicting and detecting adverse drug reactions in old age: challenges and opportunities.

    PubMed

    Mangoni, Arduino A

    2012-05-01

    Increased, often inappropriate, drug exposure, pharmacokinetic and pharmacodynamic changes, reduced homeostatic reserve and frailty increase the risk of adverse drug reactions (ADRs) in the older population, thereby imposing a significant public health burden. Predicting and diagnosing ADRs in old age presents significant challenges for the clinician, even when specific risk scoring systems are available. The picture is further compounded by the potential adverse impact of several drugs on more 'global' health indicators, for example, physical function and independence, and the fragmentation of care (e.g., increased number of treating doctors and care transitions) experienced by older patients during their clinical journey. The current knowledge of drug safety in old age is also curtailed by the lack of efficacy and safety data from pre-marketing studies. Moreover, little consideration is given to individual patients' experiences and reporting of specific ADRs, particularly in the presence of cognitive impairment. Pending additional data on these issues, the close review and monitoring of individual patients' drug prescribing, clinical status and biochemical parameters remain essential to predict and detect ADRs in old age. Recently developed strategies, for example, medication reconciliation and trigger tool methodology, have the potential for ADRs risk mitigation in this population. However, more information is required on their efficacy and applicability in different healthcare settings.

  3. Therapeutic interventions to reduce the risk of progression from prediabetes to type 2 diabetes mellitus

    PubMed Central

    Portero McLellan, Katia Cristina; Wyne, Kathleen; Villagomez, Evangelina Trejo; Hsueh, Willa A

    2014-01-01

    Clinical trials have demonstrated that it is possible to prevent diabetes through lifestyle modification, pharmacological intervention, and surgery. This review aims to summarize the effectiveness of these various therapeutic interventions in reducing the risk of progression of prediabetes to diabetes, and address the challenges to implement a diabetes prevention program at a community level. Strategies focusing on intensive lifestyle changes are not only efficient but cost-effective and/or cost-saving. Indeed, lifestyle intervention in people at high risk for type 2 diabetes mellitus (T2DM) has been successful in achieving sustained behavioral changes and a reduction in diabetes incidence even after the counseling is stopped. Although prediabetes is associated with health and economic burdens, it has not been adequately addressed by interventions or regulatory agencies in terms of prevention or disease management. Lifestyle intervention strategies to prevent T2DM should be distinct for different populations around the globe and should emphasize sex, age, ethnicity, and cultural and geographical considerations to be feasible and to promote better compliance. The translation of diabetes prevention research at a population level, especially finding the most effective methods of preventing T2DM in various societies and cultural settings remains challenging, but must be accomplished to stop this worldwide epidemic. PMID:24672242

  4. The Rotator Cuff Organ: Integrating Developmental Biology, Tissue Engineering, and Surgical Considerations to Treat Chronic Massive Rotator Cuff Tears.

    PubMed

    Rothrauff, Benjamin B; Pauyo, Thierry; Debski, Richard E; Rodosky, Mark W; Tuan, Rocky S; Musahl, Volker

    2017-08-01

    The torn rotator cuff remains a persistent orthopedic challenge, with poor outcomes disproportionately associated with chronic, massive tears. Degenerative changes in the tissues that comprise the rotator cuff organ, including muscle, tendon, and bone, contribute to the poor healing capacity of chronic tears, resulting in poor function and an increased risk for repair failure. Tissue engineering strategies to augment rotator cuff repair have been developed in an effort to improve rotator cuff healing and have focused on three principal aims: (1) immediate mechanical augmentation of the surgical repair, (2) restoration of muscle quality and contractility, and (3) regeneration of native enthesis structure. Work in these areas will be reviewed in sequence, highlighting the relevant pathophysiology, developmental biology, and biomechanics, which must be considered when designing therapeutic applications. While the independent use of these strategies has shown promise, synergistic benefits may emerge from their combined application given the interdependence of the tissues that constitute the rotator cuff organ. Furthermore, controlled mobilization of augmented rotator cuff repairs during postoperative rehabilitation may provide mechanotransductive cues capable of guiding tissue regeneration and restoration of rotator cuff function. Present challenges and future possibilities will be identified, which if realized, may provide solutions to the vexing condition of chronic massive rotator cuff tears.

  5. Measles control and elimination in Somalia: the good, the bad, and the ugly.

    PubMed

    Kamadjeu, Raoul; Assegid, Kebede; Naouri, Boubker; Mirza, Imran Raza; Hirsi, Abdurazak; Mohammed, Abdurahman; Omer, Mohammed; Dualle, Abdi Hassan; Mulugeta, Abraham

    2011-07-01

    Despite enormous challenges, Somalia has been successfully implementing accelerated measles control activities since 2005. Through innovative strategies and with the support of local and international partners, the country has shown potentials of implementing measles mortality reduction activities in complex emergencies. Measles incidence has been reduced by >80% after the measles catch-up campaigns of 2005-2007, and national reported measles routine immunization coverage with first dose measles containing vaccine has reached 59% for the first time in 2009. However, the near collapse of the health care system and the ongoing insecurity continue to hamper the implementation of recommended measles control and elimination strategies in some parts of the country, making these achievements fragile. Somalia exemplifies the challenges in meeting measles elimination goals in the World Health Organization Eastern Mediterranean region. As the region is entering its 2010 measles elimination goals, it appears necessary to establish realistic and flexible interim goals for measles control in Somalia that will take into consideration the specificities of the country. Maintaining flexibility in conducting field operations, securing financial resources, multiplying opportunities for measles vaccination, and improving disease monitoring systems will remain vital to sustain and improve current achievements. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

  6. Hegemonic masculinity: combining theory and practice in gender interventions

    PubMed Central

    Jewkes, Rachel; Morrell, Robert; Hearn, Jeff; Lundqvist, Emma; Blackbeard, David; Lindegger, Graham; Quayle, Michael; Sikweyiya, Yandisa; Gottzén, Lucas

    2015-01-01

    The concept of hegemonic masculinity has been used in gender studies since the early-1980s to explain men’s power over women. Stressing the legitimating power of consent (rather than crude physical or political power to ensure submission), it has been used to explain men’s health behaviours and the use of violence. Gender activists and others seeking to change men’s relations with women have mobilised the concept of hegemonic masculinity in interventions, but the links between gender theory and activism have often not been explored. The translation of ‘hegemonic masculinity’ into interventions is little examined. We show how, in South Africa and Sweden, the concept has been used to inform theoretically-based gender interventions and to ensure that men are brought into broader social efforts to build gender equity. We discuss the practical translational challenges of using gender theory broadly, and hegemonic masculinity in particular, in a Swedish case study, of the intervention Machofabriken [The Macho Factory], and illustrate how the concept is brought to life in this activist work with men. The concept has considerable practical application in developing a sustainable praxis of theoretically grounded interventions that are more likely to have enduring effect, but evaluating broader societal change in hegemonic masculinity remains an enduring challenge. PMID:26680535

  7. Hegemonic masculinity: combining theory and practice in gender interventions.

    PubMed

    Jewkes, Rachel; Morrell, Robert; Hearn, Jeff; Lundqvist, Emma; Blackbeard, David; Lindegger, Graham; Quayle, Michael; Sikweyiya, Yandisa; Gottzén, Lucas

    2015-01-01

    The concept of hegemonic masculinity has been used in gender studies since the early-1980s to explain men's power over women. Stressing the legitimating power of consent (rather than crude physical or political power to ensure submission), it has been used to explain men's health behaviours and the use of violence. Gender activists and others seeking to change men's relations with women have mobilised the concept of hegemonic masculinity in interventions, but the links between gender theory and activism have often not been explored. The translation of 'hegemonic masculinity' into interventions is little examined. We show how, in South Africa and Sweden, the concept has been used to inform theoretically-based gender interventions and to ensure that men are brought into broader social efforts to build gender equity. We discuss the practical translational challenges of using gender theory broadly, and hegemonic masculinity in particular, in a Swedish case study, of the intervention Machofabriken [The Macho Factory], and illustrate how the concept is brought to life in this activist work with men. The concept has considerable practical application in developing a sustainable praxis of theoretically grounded interventions that are more likely to have enduring effect, but evaluating broader societal change in hegemonic masculinity remains an enduring challenge.

  8. Editorial: 3rd Special Issue on behavior change, health, and health disparities.

    PubMed

    Higgins, Stephen T

    2016-11-01

    This Special Issue of Preventive Medicine (PM) is the 3rd that we have organized on behavior change, health, and health disparities. This is a topic of critical importance to improving U.S. population health. There is broad scientific consensus that personal behaviors such as cigarette smoking, other substance abuse, and physical inactivity/obesity are among the most important modifiable causes of chronic disease and its adverse impacts on population health. Hence, effectively promoting health-related behavior change needs to be a key component of health care research and policy. There is also broad recognition that while these problems extend throughout the population, they disproportionately impact economically disadvantaged populations and other vulnerable populations and represent a major contributor to health disparities. Thus, behavior change represents an essential step in curtailing health disparities, which receives special attention in this 3rd Special Issue. We also devote considerable space to the longstanding challenges of reducing cigarette smoking and use of other tobacco and nicotine delivery products in vulnerable populations, obesity, and for the first time food insecurity. Across each of these topics we include contributions from highly accomplished policymakers and scientists to acquaint readers with recent accomplishments as well as remaining knowledge gaps and challenges. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. A longitudinal study of smokers' exposure to cigarette smoke and the effects of spontaneous product switching.

    PubMed

    Cunningham, Anthony; Sommarström, Johan; Camacho, Oscar M; Sisodiya, Ajit S; Prasad, Krishna

    2015-06-01

    A challenge in investigating the effect of public health policies on cigarette consumption and exposure arises from variation in a smoker's exposure from cigarette to cigarette and the considerable differences between smokers. In addition, limited data are available on the effects of spontaneous product switching on a smoker's cigarette consumption and exposure to smoke constituents. Over 1000 adult smokers of the same commercial 10mg International Organization for Standardization (ISO) tar yield cigarette were recruited into the non-residential, longitudinal study across 10 cities in Germany. Cigarette consumption, mouth level exposure to tar and nicotine and biomarkers of exposure to nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone were measured every 6months over a 3 and a half year period. Cigarette consumption remained stable through the study period and did not vary significantly when smokers spontaneously switched products. Mouth level exposure decreased for smokers (n=111) who switched to cigarettes of 7mg ISO tar yield or lower. In addition, downward trends in mouth level exposure estimates were observed for smokers who did not switch cigarettes. Data from this study illustrate some of the challenges in measuring smokers' long-term exposure to smoke constituents in their everyday environment. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Lowering serum lipids via PCSK9-targeting drugs: current advances and future perspectives.

    PubMed

    He, Ni-Ya; Li, Qing; Wu, Chun-Yan; Ren, Zhong; Gao, Ya; Pan, Li-Hong; Wang, Mei-Mei; Wen, Hong-Yan; Jiang, Zhi-Sheng; Tang, Zhi-Han; Liu, Lu-Shan

    2017-03-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as neural apoptosis regulated convertase (NARC1), is a key modulator of cholesterol metabolism. PCSK9 increases the serum concentration of low-density lipoprotein cholesterol by escorting low-density lipoprotein receptors (LDLRs) from the membrane of hepatic cells into lysosomes, where the LDLRs are degraded. Owing to the importance of PCSK9 in lipid metabolism, considerable effort has been made over the past decade in developing drugs targeting PCSK9 to lower serum lipid levels. Nevertheless, some problems and challenges remain. In this review we first describes the structure and function of PCSK9 and its gene polymorphisms. We then discuss the various designs of pharmacological targets of PCSK9, including those that block the binding of PCSK9 to hepatic LDLRs (mimetic peptides, adnectins, and monoclonal antibodies), inhibit PCSK9 expression (the clustered regularly interspaced short palindromic repeats/Cas9 platform, small molecules, antisense oligonucleotides, and small interfering RNAs), and interfere with PCSK9 secretion. Finally, this review highlights future challenges in this field, including safety concerns associated with PCSK9 monoclonal antibodies, the limited utility of PCSK9 inhibitors in the central nervous system, and the cost-effectiveness of PCSK9 inhibitors.

  11. Reducing variation in decomposition odour profiling using comprehensive two-dimensional gas chromatography.

    PubMed

    Perrault, Katelynn A; Stefanuto, Pierre-Hugues; Stuart, Barbara H; Rai, Tapan; Focant, Jean-François; Forbes, Shari L

    2015-01-01

    Challenges in decomposition odour profiling have led to variation in the documented odour profile by different research groups worldwide. Background subtraction and use of controls are important considerations given the variation introduced by decomposition studies conducted in different geographical environments. The collection of volatile organic compounds (VOCs) from soil beneath decomposing remains is challenging due to the high levels of inherent soil VOCs, further confounded by the use of highly sensitive instrumentation. This study presents a method that provides suitable chromatographic resolution for profiling decomposition odour in soil by comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry using appropriate controls and field blanks. Logarithmic transformation and t-testing of compounds permitted the generation of a compound list of decomposition VOCs in soil. Principal component analysis demonstrated the improved discrimination between experimental and control soil, verifying the value of the data handling method. Data handling procedures have not been well documented in this field and standardisation would thereby reduce misidentification of VOCs present in the surrounding environment as decomposition byproducts. Uniformity of data handling and instrumental procedures will reduce analytical variation, increasing confidence in the future when investigating the effect of taphonomic variables on the decomposition VOC profile. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Medical Support for Aircraft Disaster Search and Recovery Operations at Sea: the RSN Experience.

    PubMed

    Teo, Kok Ann Colin; Chong, Tse Feng Gabriel; Liow, Min Han Lincoln; Tang, Kong Choong

    2016-06-01

    The maritime environment presents a unique set of challenges to search and recovery (SAR) operations. There is a paucity of information available to guide provision of medical support for SAR operations for aircraft disasters at sea. The Republic of Singapore Navy (RSN) took part in two such SAR operations in 2014 which showcased the value of a military organization in these operations. Key considerations in medical support for similar operations include the resultant casualty profile and challenges specific to the maritime environment, such as large distances of area of operations from land, variable sea states, and space limitations. Medical support planning can be approached using well-established disaster management life cycle phases of preparedness, mitigation, response, and recovery, which all are described in detail. This includes key areas of dedicated training and exercises, force protection, availability of air assets and chamber support, psychological care, and the forensic handling of human remains. Relevant lessons learned by RSN from the Air Asia QZ8501 search operation are also included in the description of these key areas. Teo KAC , Chong TFG , Liow MHL , Tang KC . Medical support for aircraft disaster search and recovery operations at sea: the RSN experience. Prehosp Disaster Med. 2016; 31(3):294-299.

  13. Electrical characterization of organic thin film transistors and alternative device architectures

    NASA Astrophysics Data System (ADS)

    Newman, Christopher R.

    In the last 10--15 years, organic semiconductors have evolved from experimental curiosities into viable alternatives for practical applications involving large-area and low-cost electronics such as display backplanes, electronic paper, radio frequency identification (RFID) tags, and solar cells. Many of the initially-stated goals in this field have been achieved; organic semconductors have demonstrated performance comparable to or greater than amorphous silicon (a-Si), the entrenched technology for most of the applications listed above. At present, the major obstacles remaining to commercialization of devices based on organic semiconductors involve material stability, processing considerations and optimization of the other device components (e.g. metal contacts and dielectric materials). Despite these technical achievements, significant gaps remain in our understanding of the underlying transport physics in these devices. This thesis summarizes experiments performed on organic field-effect transistors (OFETs) in an attempt to address some of these knowledge gaps. The FET, in addition to being a very useful device for practical applications (such as the driving elements in pixel backplanes), is also a very flexible architecture from an experimental standpoint. The presence of a capacitively-coupled gate electrode allows the investigation of transport physics as a function of carrier concentration. For devices in which non-idealities (i.e. carrier traps) largely dictate the observed characteristics, this is a very useful feature. Although practical OFETs are fabricated as conventional single-gate structures on an organic thin film (OTFTs), more exotic structures can often provide insights that standard OTFTs cannot. Specifically, single-crystal OFETs allow the investigation of carrier transport in the absence of grain boundaries, and double-gated OTFTs facilitate the investigation and comparison of properties across two discrete interfaces. One of the remaining challenges in terms of achieving stability inorganic semiconductors involves understanding, and hopefully minimizing, the bias stress effect of operating OTFTs. Largely ignored during the years in which research groups sought to optimize the standard device metrics of field-effect mobility, current on/off ratio, and threshold voltage, operational stability is emerging as a dominant consideration in these materials. Experiments performed with the goal of quantifying and understanding the bias-stress effect in organic semiconductors are described at the end of this thesis.

  14. An Empirical Investigation of Pre-Project Partnering Activities on Project Performance in the Software Industry

    ERIC Educational Resources Information Center

    Proffitt, Curtis K.

    2012-01-01

    Project failure remains a challenge within the software development field especially during the early stages of the IT project development. Despite the herculean efforts by project managers and organizations to identify and offset problems, projects remain plagued with issues. If these challenges are not mitigated, to a successful degree,…

  15. Some design considerations for solar-powered aircraft

    NASA Technical Reports Server (NTRS)

    Phillips, W. H.

    1980-01-01

    Performance and operating characteristics are presented for a solar powered aircraft intended to remain aloft for long periods. The critical technologies which limit the performance are identified. By using the techniques presented, the effects of variation in the system parameters are studied. Practical design consideration are discussed.

  16. Interfacial contributions in lignocellulosic firber-reinforced polyurethane composites

    Treesearch

    Timothy G. Rials; Michael P. Wolcott; John M. Nassar

    2001-01-01

    Whereas lignocellulosic fibers have received considerable attention as a reinforcing agent in thermoplastic composites, their applicability to reactive polymer systems remains of considerable interest. The hydroxyl-rich nature of natural lignocellulosic fibers suggests that they are particularly useful in thermsetting systems such as polyurethanes. To further this...

  17. Challenges Involved in the Development and Delivery of Abuse-deterrent Formulations of Opioid Analgesics.

    PubMed

    Cohen, Joshua P; Mendoza, Mario; Roland, Carl

    2018-02-01

    This commentary examines the development, regulatory, and reimbursement challenges facing abuse-deterrent formulation (ADF) products. In January 2017, the Tufts Center for the Study of Drug Development convened a roundtable to explore clinical development, regulatory, and reimbursement challenges with respect to ADFs of opioid analgesics. Roundtable participants, who included a range of pharmaceutical industry and other experts, discussed multiple challenges. First, several key clinical development challenges were identified and discussed. These challenges pertain to prodrug development and development of deterrents against oral abuse. Second, experts suggested that more clarity is needed from regulatory authorities regarding standards for proving ADF labeling claims and for being rewarded with 3-year data exclusivity. Similarly, given the substantial burdens associated with the development of postapproval evidence generation, experts raised the need for a consistent regulatory policy related to postapproval evidence generation for all ADFs (branded and generic). Third, despite the public health benefits of certain ADF products, current coverage and access policies impede patient access. Payer justification for restrictive policies appears to be based more on budget impact considerations than cost-effectiveness. Fourth, there remains a need to further expand the evidence base regarding clinical and cost-effectiveness as well as abuse deterrence in a real-world setting for all ADF products. Clinical development challenges need to be overcome with respect to novel ADF technologies, such as prodrugs and deterrents against oral abuse. More clarity is needed from regulatory authorities on labeling claims and data exclusivity eligibility with respect to ADFs. Ensuring prescriber training and awareness of various options for treating pain, including ADF products, is an important step, as is educating payers about the public health benefits of ADFs in appropriate subpopulations of pain patients. In addition, physicians may need to incorporate appropriate risk stratification methods. Finally, it is important to establish a level playing field between coverage of ADF and non-ADF products so that non-ADF products are not given preferred formulary placement. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  18. Impact of lower challenge doses of enterotoxigenic Escherichia coli on clinical outcome, intestinal colonization and immune responses in adult volunteers.

    PubMed

    Chakraborty, Subhra; Harro, Clayton; DeNearing, Barbara; Brubaker, Jessica; Connor, Sean; Maier, Nicole; Dally, Len; Flores, Jorge; Bourgeois, A Louis; Walker, Richard; Sack, David A

    2018-04-01

    A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60-70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used. Thirty subjects were randomized 1:1 to receive an oral administration of H10407 at doses of 106 or 105 CFU in bicarbonate buffer. After challenge, subjects were monitored for signs and symptoms of enteric illness and stool samples were collected to detect shedding of the challenge strain. Systemic and mucosal immune responses were measured using serum, antibody in lymphocyte supernatant and fecal samples. The attack rate was 13.3% (2/15) and 26.7% (4/15) for MSD in the 105 and 106 groups, respectively. Four MSD cases met criteria for early antibiotic treatment. All subjects but one shed the challenge strain in fecal samples. The frequency and magnitude of anti-LT toxin, CFA/I and LPS O78 immune responses were antigen, dose, severity of diarrhea and shedding levels dependent. Notably, although of lower magnitude, there were considerable immune responses in the subjects with no diarrhea. This may indicate that immune responses to asymptomatic infections of ETEC in children in the endemic countries may contribute to protection. Based on this and our prior studies, we conclude that a dose of 2x107 H10407 remains the lowest practical dose for use in future volunteer studies evaluating candidate vaccines and other preventive or therapeutic ETEC interventions. ClinicalTrials.gov NCT00844493.

  19. Impact of lower challenge doses of enterotoxigenic Escherichia coli on clinical outcome, intestinal colonization and immune responses in adult volunteers

    PubMed Central

    DeNearing, Barbara; Brubaker, Jessica; Connor, Sean; Maier, Nicole; Dally, Len; Flores, Jorge; Bourgeois, A. Louis; Walker, Richard; Sack, David A.

    2018-01-01

    A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60–70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used. Thirty subjects were randomized 1:1 to receive an oral administration of H10407 at doses of 106 or 105 CFU in bicarbonate buffer. After challenge, subjects were monitored for signs and symptoms of enteric illness and stool samples were collected to detect shedding of the challenge strain. Systemic and mucosal immune responses were measured using serum, antibody in lymphocyte supernatant and fecal samples. The attack rate was 13.3% (2/15) and 26.7% (4/15) for MSD in the 105 and 106 groups, respectively. Four MSD cases met criteria for early antibiotic treatment. All subjects but one shed the challenge strain in fecal samples. The frequency and magnitude of anti-LT toxin, CFA/I and LPS O78 immune responses were antigen, dose, severity of diarrhea and shedding levels dependent. Notably, although of lower magnitude, there were considerable immune responses in the subjects with no diarrhea. This may indicate that immune responses to asymptomatic infections of ETEC in children in the endemic countries may contribute to protection. Based on this and our prior studies, we conclude that a dose of 2x107 H10407 remains the lowest practical dose for use in future volunteer studies evaluating candidate vaccines and other preventive or therapeutic ETEC interventions. Trial registration: ClinicalTrials.gov NCT00844493. PMID:29702652

  20. Applying a framework for assessing the health system challenges to scaling up mHealth in South Africa

    PubMed Central

    2012-01-01

    Background Mobile phone technology has demonstrated the potential to improve health service delivery, but there is little guidance to inform decisions about acquiring and implementing mHealth technology at scale in health systems. Using the case of community-based health services (CBS) in South Africa, we apply a framework to appraise the opportunities and challenges to effective implementation of mHealth at scale in health systems. Methods A qualitative study reviewed the benefits and challenges of mHealth in community-based services in South Africa, through a combination of key informant interviews, site visits to local projects and document reviews. Using a framework adapted from three approaches to reviewing sustainable information and communication technology (ICT), the lessons from local experience and elsewhere formed the basis of a wider consideration of scale up challenges in South Africa. Results Four key system dimensions were identified and assessed: government stewardship and the organisational, technological and financial systems. In South Africa, the opportunities for successful implementation of mHealth include the high prevalence of mobile phones, a supportive policy environment for eHealth, successful use of mHealth for CBS in a number of projects and a well-developed ICT industry. However there are weaknesses in other key health systems areas such as organisational culture and capacity for using health information for management, and the poor availability and use of ICT in primary health care. The technological challenges include the complexity of ensuring interoperability and integration of information systems and securing privacy of information. Finally, there are the challenges of sustainable financing required for large scale use of mobile phone technology in resource limited settings. Conclusion Against a background of a health system with a weak ICT environment and limited implementation capacity, it remains uncertain that the potential benefits of mHealth for CBS would be retained with immediate large-scale implementation. Applying a health systems framework facilitated a systematic appraisal of potential challenges to scaling up mHealth for CBS in South Africa and may be useful for policy and practice decision-making in other low- and middle-income settings. PMID:23126370

  1. Hydrogel scaffolds for tissue engineering: Progress and challenges

    PubMed Central

    El-Sherbiny, Ibrahim M.; Yacoub, Magdi H.

    2013-01-01

    Designing of biologically active scaffolds with optimal characteristics is one of the key factors for successful tissue engineering. Recently, hydrogels have received a considerable interest as leading candidates for engineered tissue scaffolds due to their unique compositional and structural similarities to the natural extracellular matrix, in addition to their desirable framework for cellular proliferation and survival. More recently, the ability to control the shape, porosity, surface morphology, and size of hydrogel scaffolds has created new opportunities to overcome various challenges in tissue engineering such as vascularization, tissue architecture and simultaneous seeding of multiple cells. This review provides an overview of the different types of hydrogels, the approaches that can be used to fabricate hydrogel matrices with specific features and the recent applications of hydrogels in tissue engineering. Special attention was given to the various design considerations for an efficient hydrogel scaffold in tissue engineering. Also, the challenges associated with the use of hydrogel scaffolds were described. PMID:24689032

  2. Challenges and Considerations Related to Studying Dementia in Blacks/African Americans.

    PubMed

    Ighodaro, Eseosa T; Nelson, Peter T; Kukull, Walter A; Schmitt, Frederick A; Abner, Erin L; Caban-Holt, Allison; Bardach, Shoshana H; Hord, Derrick C; Glover, Crystal M; Jicha, Gregory A; Van Eldik, Linda J; Byrd, Alexander X; Fernander, Anita

    2017-01-01

    Blacks/African Americans have been reported to be ∼2-4 times more likely to develop clinical Alzheimer's disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses. Here we provide a selected historical background, discuss challenges, present opportunities, and suggest considerations for studying health outcomes among racial/ethnic groups. We encourage neuroscientists to consider shifting away from using biologic determination to interpret data, and work instead toward a paradigm of incorporating both biological and socio-environmental factors known to affect health outcomes with the goal of understanding and improving dementia treatments for Blacks/African Americans and other underserved populations.

  3. Considerations of Alloy 617 Application in the Gen IV Nuclear Reactor Systems - Part I: Mechanical Property Challenges

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

    Ren, Weiju

    2010-01-01

    Alloy 617 is currently considered as a leading candidate material for high temperature components in the Gen IV Nuclear Reactor Systems. Because of the unprecedented severe working conditions beyond its commercial service experience required by the Gen IV systems, the alloy faces various challenges in both mechanical and metallurgical properties. This paper, as Part I of the discussion, is focused on the challenges and issues in the mechanical properties of Alloy 617 for the intended nuclear application. Considerations are given in details in its mechanical property data scatter, low creep strength in the desired high temperature range, lack of longtermmore » creep curves, high loading rate dependency, and preponderant tertiary creep. Some research and development activities are suggested with discussions on their viability to satisfy the Gen IV Nuclear Reactor System needs in near future and in the long run.« less

  4. Endodontic and Clinical Considerations in the Management of Variable Anatomy in Mandibular Premolars: A Literature Review

    PubMed Central

    Hammo, Mohammad

    2014-01-01

    Mandibular premolars are known to have numerous anatomic variations of their roots and root canals, which are a challenge to treat endodontically. The paper reviews literature to detail the various clinically relevant anatomic considerations with detailed techniques and methods to successfully manage these anomalies. An emphasis and detailed description of every step of treatment including preoperative diagnosis, intraoperative identification and management, and surgical endodontic considerations for the successful management of these complex cases have been included. PMID:24895584

  5. Staff experiences of closing out a clinical trial involving withdrawal of treatment: qualitative study.

    PubMed

    Lawton, Julia; White, David; Rankin, David; Elliott, Jackie; Taylor, Carolin; Cooper, Cindy; Heller, Simon; Hallowell, Nina

    2017-02-07

    The ending of a clinical trial may be challenging, particularly if staff are required to withdraw the investigated treatment(s); however, this aspect of trial work is surprisingly under-researched. To address this gap, we explored the experiences of staff involved in closing out a trial that entailed withdrawal of treatment (insulin pumps) from some patients. Interviews were conducted with n = 22 staff, recruited from seven trial sites. Data were analysed thematically. Staff described a myriad of ethical and emotional challenges at closeout, many of which had been unforeseen when the trial began. A key challenge for staff was that, while patients gave their agreement to participate on the understanding that pump treatment could be withdrawn, they often found themselves benefitting from this regimen in ways they could not have foreseen. Hence, as the trial progressed, patients became increasingly anxious about withdrawal of treatment. This situation forced staff to consider whether the consent patients had given at the outset remained valid; it also presented them with a dilemma at closeout because many of those who had wanted to remain on a pump did not meet the clinical criteria required for post-trial funding. When deciding whether to withdraw treatment, staff not only had to take funding pressures and patient distress into account, but they also found themselves caught between an ethic of Hippocratic individualism and one of utilitarianism. These conflicting pressures and ethical considerations resulted in staff decision-making varying across the sites, an issue that some described as a further source of ethical unease. Staff concluded that, had there been more advanced planning and discussion, and greater accountability to an ethics committee, some of the challenges they had confronted at closeout could have been lessened or even prevented. The same kinds of ethical issues that may vex staff at the beginning of a trial (e.g. patients having unrealistic expectations of trial participation; staff experiencing conflicts between research and clinical roles) may re-present themselves at the end. To safeguard the wellbeing of staff and patients, greater planning, coordination and ethical oversight should go into the closeout of trials involving withdrawal of treatment(s). International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ISRCTN61215213 . Registered on 11 May 2011.

  6. Functional Basis for Efficient Physical Layer Classical Control in Quantum Processors

    NASA Astrophysics Data System (ADS)

    Ball, Harrison; Nguyen, Trung; Leong, Philip H. W.; Biercuk, Michael J.

    2016-12-01

    The rapid progress seen in the development of quantum-coherent devices for information processing has motivated serious consideration of quantum computer architecture and organization. One topic which remains open for investigation and optimization relates to the design of the classical-quantum interface, where control operations on individual qubits are applied according to higher-level algorithms; accommodating competing demands on performance and scalability remains a major outstanding challenge. In this work, we present a resource-efficient, scalable framework for the implementation of embedded physical layer classical controllers for quantum-information systems. Design drivers and key functionalities are introduced, leading to the selection of Walsh functions as an effective functional basis for both programing and controller hardware implementation. This approach leverages the simplicity of real-time Walsh-function generation in classical digital hardware, and the fact that a wide variety of physical layer controls, such as dynamic error suppression, are known to fall within the Walsh family. We experimentally implement a real-time field-programmable-gate-array-based Walsh controller producing Walsh timing signals and Walsh-synthesized analog waveforms appropriate for critical tasks in error-resistant quantum control and noise characterization. These demonstrations represent the first step towards a unified framework for the realization of physical layer controls compatible with large-scale quantum-information processing.

  7. Health Surveys Using Mobile Phones in Developing Countries: Automated Active Strata Monitoring and Other Statistical Considerations for Improving Precision and Reducing Biases.

    PubMed

    Labrique, Alain; Blynn, Emily; Ahmed, Saifuddin; Gibson, Dustin; Pariyo, George; Hyder, Adnan A

    2017-05-05

    In low- and middle-income countries (LMICs), historically, household surveys have been carried out by face-to-face interviews to collect survey data related to risk factors for noncommunicable diseases. The proliferation of mobile phone ownership and the access it provides in these countries offers a new opportunity to remotely conduct surveys with increased efficiency and reduced cost. However, the near-ubiquitous ownership of phones, high population mobility, and low cost require a re-examination of statistical recommendations for mobile phone surveys (MPS), especially when surveys are automated. As with landline surveys, random digit dialing remains the most appropriate approach to develop an ideal survey-sampling frame. Once the survey is complete, poststratification weights are generally applied to reduce estimate bias and to adjust for selectivity due to mobile ownership. Since weights increase design effects and reduce sampling efficiency, we introduce the concept of automated active strata monitoring to improve representativeness of the sample distribution to that of the source population. Although some statistical challenges remain, MPS represent a promising emerging means for population-level data collection in LMICs. ©Alain Labrique, Emily Blynn, Saifuddin Ahmed, Dustin Gibson, George Pariyo, Adnan A Hyder. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.05.2017.

  8. Genetic polymorphisms and their association with brain and behavioural measures in heterogeneous stock mice

    PubMed Central

    Janecka, Magdalena; Marzi, Sarah J.; Parsons, Michael J.; Liu, Lin; Paya-Cano, Jose L.; Smith, Rebecca G.; Fernandes, Cathy; Schalkwyk, Leonard C.

    2017-01-01

    Although the search for quantitative trait loci for behaviour remains a considerable challenge, the complicated genetic architecture of quantitative traits is beginning to be understood. The current project utilised heterogeneous stock (HS) male mice (n = 580) to investigate the genetic basis for brain weights, activity, anxiety and cognitive phenotypes. We identified 126 single nucleotide polymorphisms (SNPs) in genes involved in regulation of neurotransmitter systems, nerve growth/death and gene expression, and subsequently investigated their associations with changes in behaviour and/or brain weights in our sample. We found significant associations between four SNP-phenotype pairs, after controlling for multiple testing. Specificity protein 2 (Sp2, rs3708840), tryptophan hydroxylase 1 (Tph1, rs262731280) and serotonin receptor 3A (Htr3a, rs50670893) were associated with activity/anxiety behaviours, and microtubule-associated protein 2 (Map2, rs13475902) was associated with cognitive performance. All these genes except for Tph1 were expressed in the brain above the array median, and remained significantly associated with relevant behaviours after controlling for the family structure. Additionally, we found evidence for a correlation between Htr3a expression and activity. We discuss our findings in the light of the advantages and limitations of currently available mouse genetic tools, suggesting further directions for association studies in rodents. PMID:28145470

  9. Convection-enhanced delivery for the treatment of glioblastoma.

    PubMed

    Vogelbaum, Michael A; Aghi, Manish K

    2015-03-01

    Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low-positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Next generation metronomic chemotherapy-report from the Fifth Biennial International Metronomic and Anti-angiogenic Therapy Meeting, 6-8 May 2016, Mumbai.

    PubMed

    Pantziarka, Pan; Hutchinson, Lisa; André, Nicolas; Benzekry, Sébastien; Bertolini, Francesco; Bhattacharjee, Atanu; Chiplunkar, Shubhada; Duda, Dan G; Gota, Vikram; Gupta, Sudeep; Joshi, Amit; Kannan, Sadhana; Kerbel, Robert; Kieran, Mark; Palazzo, Antonella; Parikh, Aparna; Pasquier, Eddy; Patil, Vijay; Prabhash, Kumar; Shaked, Yuval; Sholler, Giselle Saulnier; Sterba, Jaroslav; Waxman, David J; Banavali, Shripad

    2016-01-01

    The 5 th Biennial Metronomic and Anti-angiogenic Therapy Meeting was held on 6 th - 8 th May in the Indian city of Mumbai. The meeting brought together a wide range of clinicians and researchers interested in metronomic chemotherapy, anti-angiogenics, drug repurposing and combinations thereof. Clinical experiences, including many from India, were reported and discussed in three symposia covering breast cancer, head and neck cancers and paediatrics. On the pre-clinical side research into putative mechanisms of action, and the interactions between low dose metronomic chemotherapy and angiogenesis and immune responses, were discussed in a number of presentations. Drug repurposing was discussed both in terms of clinical results, particularly with respect to angiosarcoma and high-risk neuroblastoma, and in pre-clinical settings, particularly the potential for peri-operative interventions. However, it was clear that there remain a number of key areas of challenge, particularly in terms of definitions, perceptions in the wider oncological community, mechanisms of action and predictive biomarkers. While the potential for metronomics and drug repurposing in low and middle income countries remains a key theme, it is clear that there is also considerable potential for clinically relevant improvements in patient outcomes even in high income economies.

  11. Towards international consensus on patient harm: perspectives on pressure injury policy.

    PubMed

    Jackson, Debra; Hutchinson, Marie; Barnason, Susan; Li, William; Mannix, Judy; Neville, Stephen; Piper, Donella; Power, Tamara; Smith, Graeme D; Usher, Kim

    2016-10-01

    To analyse influential policies that inform practice related to pressure injury management in Australia, England, Hong Kong, New Zealand, Scotland and the United States of America. Pressure injuries are associated with significant harm to patients, and carry economic consequences for the health sector. Internationally, preventing and managing pressure injuries is a key nursing activity and quality indicator. Comparative review and synthesis of pressure injury policies that inform practice. The predominant focus of policy is on patient risk assessment, compliance with documentation and pressure relief. Financial penalty for institutions is emerging as a strategy where pressure injuries occur. Comparisons of prevalence rates are hampered by the lack of consensus on data collection and reporting. To date there has been little evaluation of policy implementation and implemented policy strategies, associated guidelines remain founded upon expert opinion and low-level evidence. The pressure injury policy agenda has fostered a discourse of attention to incidents, compliance and penalty (sanctions). Prevention and intervention strategies are informed by technical and biomedical interpretations of patient risk and harm, with little attention given to the nature or design of nursing work. Considerable challenges remain if this policy agenda is successfully to eliminate pressure injury as a source of patient harm. © 2016 John Wiley & Sons Ltd.

  12. Building a mechanistic understanding of predation with GPS-based movement data.

    PubMed

    Merrill, Evelyn; Sand, Håkan; Zimmermann, Barbara; McPhee, Heather; Webb, Nathan; Hebblewhite, Mark; Wabakken, Petter; Frair, Jacqueline L

    2010-07-27

    Quantifying kill rates and sources of variation in kill rates remains an important challenge in linking predators to their prey. We address current approaches to using global positioning system (GPS)-based movement data for quantifying key predation components of large carnivores. We review approaches to identify kill sites from GPS movement data as a means to estimate kill rates and address advantages of using GPS-based data over past approaches. Despite considerable progress, modelling the probability that a cluster of GPS points is a kill site is no substitute for field visits, but can guide our field efforts. Once kill sites are identified, time spent at a kill site (handling time) and time between kills (killing time) can be determined. We show how statistical models can be used to investigate the influence of factors such as animal characteristics (e.g. age, sex, group size) and landscape features on either handling time or killing efficiency. If we know the prey densities along paths to a kill, we can quantify the 'attack success' parameter in functional response models directly. Problems remain in incorporating the behavioural complexity derived from GPS movement paths into functional response models, particularly in multi-prey systems, but we believe that exploring the details of GPS movement data has put us on the right path.

  13. Effects of a dual-pump crude-oil recovery system, Bemidji, Minnesota, USA

    USGS Publications Warehouse

    Delin, Geoffrey N.; Herkelrath, William N.

    2014-01-01

    A crude-oil spill occurred in 1979 when a pipeline burst near Bemidji, MN. In 1998, the pipeline company installed a dual-pump recovery system designed to remove crude oil remaining in the subsurface at the site. The remediation from 1999 to 2003 resulted in removal of about 115,000 L of crude oil, representing between 36% and 41% of the volume of oil (280,000 to 316,000 L) estimated to be present in 1998. Effects of the 1999 to 2003 remediation on the dissolved plume were evaluated using measurements of oil thicknesses in wells plus measurements of dissolved oxygen in groundwater. Although the recovery system decreased oil thicknesses in the immediate vicinity of the remediation wells, average oil thicknesses measured in wells were largely unaffected. Dissolved-oxygen measurements indicate that a secondary plume was caused by disposal of the pumped water in an upgradient infiltration gallery; this plume expanded rapidly immediately following the start of the remediation in 1999. The result was expansion of the anoxic zone of groundwater upgradient and beneath the existing natural attenuation plume. Oil-phase recovery at this site was shown to be challenging, and considerable volumes of mobile and entrapped oil remain in the subsurface despite remediation efforts.

  14. Reliability Considerations for Ultra- Low Power Space Applications

    NASA Technical Reports Server (NTRS)

    White, Mark; Johnston, Allan

    2012-01-01

    NASA, the aerospace community, and other high reliability (hi-rel) users of advanced microelectronic products face many challenges as technology continues to scale into the deep sub- micron region and ULP devices are sought after. Technology trends, ULP microelectronics, scaling and performance tradeoffs, reliability considerations, and spacecraft environments will be presented from a ULP perspective for space applications.

  15. Methodological developments in searching for studies for systematic reviews: past, present and future?

    PubMed

    Lefebvre, Carol; Glanville, Julie; Wieland, L Susan; Coles, Bernadette; Weightman, Alison L

    2013-09-25

    The Cochrane Collaboration was established in 1993, following the opening of the UK Cochrane Centre in 1992, at a time when searching for studies for inclusion in systematic reviews was not well-developed. Review authors largely conducted their own searches or depended on medical librarians, who often possessed limited awareness and experience of systematic reviews. Guidance on the conduct and reporting of searches was limited. When work began to identify reports of randomized controlled trials (RCTs) for inclusion in Cochrane Reviews in 1992, there were only approximately 20,000 reports indexed as RCTs in MEDLINE and none indexed as RCTs in Embase. No search filters had been developed with the aim of identifying all RCTs in MEDLINE or other major databases. This presented The Cochrane Collaboration with a considerable challenge in identifying relevant studies.Over time, the number of studies indexed as RCTs in the major databases has grown considerably and the Cochrane Central Register of Controlled Trials (CENTRAL) has become the best single source of published controlled trials, with approximately 700,000 records, including records identified by the Collaboration from Embase and MEDLINE. Search filters for various study types, including systematic reviews and the Cochrane Highly Sensitive Search Strategies for RCTs, have been developed. There have been considerable advances in the evidence base for methodological aspects of information retrieval. The Cochrane Handbook for Systematic Reviews of Interventions now provides detailed guidance on the conduct and reporting of searches. Initiatives across The Cochrane Collaboration to improve the quality inter alia of information retrieval include: the recently introduced Methodological Expectations for Cochrane Intervention Reviews (MECIR) programme, which stipulates 'mandatory' and 'highly desirable' standards for various aspects of review conduct and reporting including searching, the development of Standard Training Materials for Cochrane Reviews and work on peer review of electronic search strategies. Almost all Cochrane Review Groups and some Cochrane Centres and Fields now have a Trials Search Co-ordinator responsible for study identification and medical librarians and other information specialists are increasingly experienced in searching for studies for systematic reviews.Prospective registration of clinical trials is increasing and searching trials registers is now mandatory for Cochrane Reviews, where relevant. Portals such as the WHO International Clinical Trials Registry Platform (ICTRP) are likely to become increasingly attractive, given concerns about the number of trials which may not be registered and/or published. The importance of access to information from regulatory and reimbursement agencies is likely to increase. Cross-database searching, gateways or portals and improved access to full-text databases will impact on how searches are conducted and reported, as will services such as Google Scholar, Scopus and Web of Science. Technologies such as textual analysis, semantic analysis, text mining and data linkage will have a major impact on the search process but efficient and effective updating of reviews may remain a challenge.In twenty years' time, we envisage that the impact of universal social networking, as well as national and international legislation, will mean that all trials involving humans will be registered at inception and detailed trial results will be routinely available to all. Challenges will remain, however, to ensure the discoverability of relevant information in diverse and often complex sources and the availability of metadata to provide the most efficient access to information. We envisage an ongoing role for information professionals as experts in identifying new resources, researching efficient ways to link or mine them for relevant data and managing their content for the efficient production of systematic reviews.

  16. Methodological developments in searching for studies for systematic reviews: past, present and future?

    PubMed Central

    2013-01-01

    The Cochrane Collaboration was established in 1993, following the opening of the UK Cochrane Centre in 1992, at a time when searching for studies for inclusion in systematic reviews was not well-developed. Review authors largely conducted their own searches or depended on medical librarians, who often possessed limited awareness and experience of systematic reviews. Guidance on the conduct and reporting of searches was limited. When work began to identify reports of randomized controlled trials (RCTs) for inclusion in Cochrane Reviews in 1992, there were only approximately 20,000 reports indexed as RCTs in MEDLINE and none indexed as RCTs in Embase. No search filters had been developed with the aim of identifying all RCTs in MEDLINE or other major databases. This presented The Cochrane Collaboration with a considerable challenge in identifying relevant studies. Over time, the number of studies indexed as RCTs in the major databases has grown considerably and the Cochrane Central Register of Controlled Trials (CENTRAL) has become the best single source of published controlled trials, with approximately 700,000 records, including records identified by the Collaboration from Embase and MEDLINE. Search filters for various study types, including systematic reviews and the Cochrane Highly Sensitive Search Strategies for RCTs, have been developed. There have been considerable advances in the evidence base for methodological aspects of information retrieval. The Cochrane Handbook for Systematic Reviews of Interventions now provides detailed guidance on the conduct and reporting of searches. Initiatives across The Cochrane Collaboration to improve the quality inter alia of information retrieval include: the recently introduced Methodological Expectations for Cochrane Intervention Reviews (MECIR) programme, which stipulates 'mandatory’ and 'highly desirable’ standards for various aspects of review conduct and reporting including searching, the development of Standard Training Materials for Cochrane Reviews and work on peer review of electronic search strategies. Almost all Cochrane Review Groups and some Cochrane Centres and Fields now have a Trials Search Co-ordinator responsible for study identification and medical librarians and other information specialists are increasingly experienced in searching for studies for systematic reviews. Prospective registration of clinical trials is increasing and searching trials registers is now mandatory for Cochrane Reviews, where relevant. Portals such as the WHO International Clinical Trials Registry Platform (ICTRP) are likely to become increasingly attractive, given concerns about the number of trials which may not be registered and/or published. The importance of access to information from regulatory and reimbursement agencies is likely to increase. Cross-database searching, gateways or portals and improved access to full-text databases will impact on how searches are conducted and reported, as will services such as Google Scholar, Scopus and Web of Science. Technologies such as textual analysis, semantic analysis, text mining and data linkage will have a major impact on the search process but efficient and effective updating of reviews may remain a challenge. In twenty years’ time, we envisage that the impact of universal social networking, as well as national and international legislation, will mean that all trials involving humans will be registered at inception and detailed trial results will be routinely available to all. Challenges will remain, however, to ensure the discoverability of relevant information in diverse and often complex sources and the availability of metadata to provide the most efficient access to information. We envisage an ongoing role for information professionals as experts in identifying new resources, researching efficient ways to link or mine them for relevant data and managing their content for the efficient production of systematic reviews. PMID:24066664

  17. Interfacial contributions in lignocellulosic fiber-reinforced polyurethane composites

    Treesearch

    Timothy G. Rials; Michael P. Wolcott; John M. Nassar

    2001-01-01

    Whereas lignocellulosic fibers have received considerable attention as a rein- forcing agent in thermoplastic composites, their applicability to reactive polymer systems remains of considerable interest. The hydroxyl-rich nature of natural lignocellulosic fibers suggests that they are particularly useful in thermosetting systems such as polyurethanes. To further this...

  18. Navy DDG-51 and DDG-1000 Destroyer Programs: Background and Issues for Congress

    DTIC Science & Technology

    2012-03-02

    challenging ship redesign as well as a new power and cooling architecture coupled with the challenges to construct such a dense ship, will make...costs. Our prior work has shown that construction of lead ships is challenging , the risk of cost growth is high, and having sufficient construction...not include a thorough trade-off analysis that would compare the relative costs and benefits of different solutions under consideration or provide

  19. Strategies for Improving Indigenous Financial Literacy in Schools

    ERIC Educational Resources Information Center

    Bin-Sallik, MaryAnn; Adams, Isabella; Vemuri, Siva Ram

    2004-01-01

    The Indigenous Australian population is not only considerably younger than the non-Indigenous population but is also on the rise. The challenge for many is to provide the kind of education that equips young Indigenous Australians with the necessary skills for managing their money. This challenge is further compounded, as the adult Indigenous…

  20. Taking over Someone Else's E-Learning Design: Challenges Trigger Change in E-Learning Beliefs and Practices

    ERIC Educational Resources Information Center

    Scott, Karen M.

    2014-01-01

    As universities invest in the development of e-learning resources, e-learning sustainability has come under consideration. This has largely focused on the challenges and facilitators of organisational and technological sustainability and scalability, and professional development. Little research has examined the experience of a teacher dealing…

  1. Challenges for an Interdisciplinary Consideration of Cognitive Training

    ERIC Educational Resources Information Center

    Birney, Damian Patrick

    2015-01-01

    Whether fluid cognitive functions are malleable has been a topic of ongoing debate for at least the past 100 years. Ever-evolving technology has led to new and diverse fields of investigation entering this debate. There are significant advantages to be gained by integrating different scientific paradigms, but there are also significant challenges.…

  2. Cooperative Learning in Middle Schools: Interrelationship of Relationships and Achievement

    ERIC Educational Resources Information Center

    Johnson, David W.; Johnson, Roger T.; Roseth, Cary

    2010-01-01

    When students enter middle school, they face 2 major challenges, one involving the biological, cognitive, and socioemotional changes they are going through, and another involving the transition from elementary to middle school. Peer learning has considerable influence on how well they manage these challenges. The research that exists on peer…

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

    ERIC Educational Resources Information Center

    Heywood, David; Parker, Joan; Rowlands, Mark

    2013-01-01

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

  4. The Challenge of Content Creation to Facilitate Personalized E-Learning Experiences

    ERIC Educational Resources Information Center

    Turker, Ali; Gorgun, Ilhami; Conlan, Owen

    2006-01-01

    The runtime creation of pedagogically coherent learning content for an individual learner's needs and preferences is a considerable challenge. By selecting and combining appropriate learning assets into a new learning object such needs and preferences may be accounted for. However, to assure coherence, these objects should be consumed within…

  5. Individual Characteristics and Service Expenditure on Challenging Behaviour for Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Hassiotis, Angela; Parkes, Charles; Jones, Lee; Fitzgerald, Brian; Romeo, Renee

    2008-01-01

    Background: English policy argues that people with intellectual disabilities should be supported in their local communities. There is considerable evidence that this aspiration is not being achieved. This paper seeks to look at the subsection of people with intellectual disabilities who have expensive care needs because of challenging behaviour,…

  6. Domestic Violence and Sexual Assault Services: Historical Concerns and Contemporary Challenges

    ERIC Educational Resources Information Center

    Macy, Rebecca J.; Giattina, Mary C.; Parish, Susan L.; Crosby, Carmen

    2010-01-01

    More than 20 years ago, concerns were raised about whether domestic violence and sexual assault agencies need for stable funding would conflict with the values that initiated these respective movements. Since then, the movements have evolved considerably. Therefore, it is timely to investigate the challenges domestic violence and sexual assault…

  7. Reading Comprehension Is Embodied: Theoretical and Practical Considerations

    ERIC Educational Resources Information Center

    Sadoski, Mark

    2018-01-01

    In this review, I advance the embodied cognition movement in cognitive psychology as both a challenge and an invitation for the study of reading comprehension. Embodied cognition challenges theories which assume that mental operations are based in a common, abstract, amodal code of propositions and schemata. Based on growing research in behavioral…

  8. Post-Adoption Issues Related to Cloud-Based IT Solutions: A Multi-Method Investigation

    ERIC Educational Resources Information Center

    Xiao, Xiao

    2013-01-01

    Due to their low cost of implementation and considerable elasticity, cloud-based IT solutions are being widely adopted or considered in organizations across various industries. However, such IT solutions bring forth several unique challenges--challenges that make it difficult for organizations to achieve successful utilization of cloud-based…

  9. Challenges Faced by Teachers Implementing Socio-Scientific Issues as Core Elements in Their Classroom Practices

    ERIC Educational Resources Information Center

    Bossér, Ulrika; Lundin, Mattias; Lindahl, Mats; Linder, Cedric

    2015-01-01

    Teachers may face considerable challenges when implementing socio-scientific issues (SSI) in their classroom practices, such as incorporating student-centred teaching practices and exploring knowledge and values in the context of socioscientific issues. This year-long study explores teachers' reflections on the process of developing their…

  10. Riparian fuel treatments in the western USA: Challenges and considerations

    Treesearch

    Kathleen A. Dwire; Kristen E. Meyer; Gregg Riegel; Timothy Burton

    2016-01-01

    Fuel reduction treatments are being conducted throughout watersheds of the western United States to reduce hazardous fuels in efforts to decrease the risk of high-severity fire. The number of fuel reduction projects that include near-stream environments is increasing, bringing new challenges to riparian management. Riparian areas are protected by administrative...

  11. Developmental Changes in the Consideration of Sample Diversity in Inductive Reasoning

    ERIC Educational Resources Information Center

    Rhodes, Marjorie; Gelman, Susan A.; Brickman, Daniel

    2008-01-01

    Determining whether a sample provides a good basis for broader generalizations is a basic challenge of inductive reasoning. Adults apply a diversity-based strategy to this challenge, expecting diverse samples to be a better basis for generalization than homogeneous samples. For example, adults expect that a property shared by two diverse mammals…

  12. ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests.

    PubMed

    Coates, Allan L; Wanger, Jack; Cockcroft, Donald W; Culver, Bruce H; Diamant, Zuzana; Gauvreau, Gail; Hall, Graham L; Hallstrand, Teal S; Horvath, Ildiko; de Jongh, Frans H C; Joos, Guy; Kaminsky, David A; Laube, Beth L; Leuppi, Joerg D; Sterk, Peter J

    2017-05-01

    This international task force report updates general considerations for bronchial challenge testing and the performance of the methacholine challenge test. There are notable changes from prior recommendations in order to accommodate newer delivery devices. Rather than basing the test result upon a methacholine concentration (provocative concentration (PC 20 ) causing a 20% fall in forced expiratory volume in 1 s (FEV 1 )), the new recommendations base the result upon the delivered dose of methacholine causing a 20% fall in FEV 1 (provocative dose (PD 20 )). This end-point allows comparable results from different devices or protocols, thus any suitable nebuliser or dosimeter may be used, so long as the delivery characteristics are known. Inhalation may be by tidal breathing using a breath-actuated or continuous nebuliser for 1 min (or more), or by a dosimeter with a suitable breath count. Tests requiring maximal inhalations to total lung capacity are not recommended because the bronchoprotective effect of a deep breath reduces the sensitivity of the test. Copyright ©ERS 2017.

  13. Geohazards in the IYPE: An Example of a Holistic Approach to Achieving a Vision (Invited)

    NASA Astrophysics Data System (ADS)

    Woodfork, L. D.; Eder, W.; Janoschek, W.

    2009-12-01

    The International Year of Planet Earth (IYPE), a triennium (2007 - 2009), is a joint initiative between UNESCO and the IUGS. The central year, 2008, was proclaimed by the UN General Assembly to be The International Year of Planet Earth (for complete details, visit www.yearofplanetearth.org). Two major foci comprise the IYPE: a science/research initiative on 10 broad, multidisciplinary, socially relevant programs, one of which was Hazards. The second was outreach/public education to make the science/research relevant to a broader audience, including the general public, and in particular, decision makers at all levels of government through the local, state/province, national, and international levels. The vision of IYPE was to make its subtitle, "Earth Sciences for Society," not just a slogan but an influential global reality. Geohazards, however defined, are pervasive global phenomena ranging from small nuisance situations, to those with significant financial considerations, to huge, catastrophic events involving enormous loss of life and tremendous financial loss. Clearly, to attempt to effectively deal with geohazards in modern society, we must (1) Maximize public awareness of the appreciation of the danger involved in various situations (2) Minimize the risk through appropriate public policy and personal responsibility (3) Mitigate the danger and damage that might occur despite our best efforts to accomplish (1) and (2). Over the past three years, the IYPE has pursued a holistic approach to dealing with geohazards, involving science/research and outreach/education through the activities of national committees for the IYPE in 80 countries around the globe. Now as the IYPE draws rapidly to a close at the end of this calendar year, we have accomplished much using this holistic approach toward our noble vision of making "Earth Sciences for Society" a reality. Although a significant record of accomplishment and a legacy of the IYPE remain, in my view, much still remains to be done. A global framework linking 400,000 geoscientists has been established, but the fulfillment of making "Earth Sciences for Society" remains a continuing challenge. I personally believe that follow-on opportunities provided by IYPE are obvious and should be pursued. We should not and cannot simply rest on our laurels. The IYPE has been a good start toward meeting challenges and opening future opportunities, so stay involved and remain a part of it.

  14. Radiation Shielding for Nuclear Thermal Propulsion

    NASA Technical Reports Server (NTRS)

    Caffrey, Jarvis A.

    2016-01-01

    Design and analysis of radiation shielding for nuclear thermal propulsion has continued at Marshall Space Flight Center. A set of optimization tools are in development, and strategies for shielding optimization will be discussed. Considerations for the concurrent design of internal and external shielding are likely required for a mass optimal shield design. The task of reducing radiation dose to crew from a nuclear engine is considered to be less challenging than the task of thermal mitigation for cryogenic propellant, especially considering the likely implementation of additional crew shielding for protection from solar particles and cosmic rays. Further consideration is thus made for the thermal effects of radiation absorption in cryogenic propellant. Materials challenges and possible methods of manufacturing are also discussed.

  15. HSR Aerodynamic Performance Status and Challenges

    NASA Technical Reports Server (NTRS)

    Gilbert, William P.; Antani, Tony; Ball, Doug; Calloway, Robert L.; Snyder, Phil

    1999-01-01

    This paper describes HSR (High Speed Research) Aerodynamic Performance Status and Challenges. The topics include: 1) Aero impact on HSR; 2) Goals and Targets; 3) Progress and Status; and 4) Remaining Challenges. This paper is presented in viewgraph form.

  16. [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.

  17. Remaining Useful Life Estimation in Prognosis: An Uncertainty Propagation Problem

    NASA Technical Reports Server (NTRS)

    Sankararaman, Shankar; Goebel, Kai

    2013-01-01

    The estimation of remaining useful life is significant in the context of prognostics and health monitoring, and the prediction of remaining useful life is essential for online operations and decision-making. However, it is challenging to accurately predict the remaining useful life in practical aerospace applications due to the presence of various uncertainties that affect prognostic calculations, and in turn, render the remaining useful life prediction uncertain. It is challenging to identify and characterize the various sources of uncertainty in prognosis, understand how each of these sources of uncertainty affect the uncertainty in the remaining useful life prediction, and thereby compute the overall uncertainty in the remaining useful life prediction. In order to achieve these goals, this paper proposes that the task of estimating the remaining useful life must be approached as an uncertainty propagation problem. In this context, uncertainty propagation methods which are available in the literature are reviewed, and their applicability to prognostics and health monitoring are discussed.

  18. A Comprehensive Tool for Exploring the Availability, Scalability and Growth Potential of Conventional and Renewable Energy Sources and Technologies

    NASA Astrophysics Data System (ADS)

    Jack-Scott, E.; Arnott, J. C.; Katzenberger, J.; Davis, S. J.; Delman, E.

    2015-12-01

    It has been a generational challenge to simultaneously meet the world's energy requirements, while remaining within the bounds of acceptable cost and environmental impact. To this end, substantial research has explored various energy futures on a global scale, leaving decision-makers and the public overwhelmed by information on energy options. In response, this interactive energy table was developed as a comprehensive resource through which users can explore the availability, scalability, and growth potentials of all energy technologies currently in use or development. Extensive research from peer-reviewed papers and reports was compiled and summarized, detailing technology costs, technical considerations, imminent breakthroughs, and obstacles to integration, as well as political, social, and environmental considerations. Energy technologies fall within categories of coal, oil, natural gas, nuclear, solar, wind, hydropower, ocean, geothermal and biomass. In addition to 360 expandable cells of cited data, the interactive table also features educational windows with background information on each energy technology. The table seeks not to advocate for specific energy futures, but to succinctly and accurately centralize peer-reviewed research and information in an interactive, accessible resource. With this tool, decision-makers, researchers and the public alike can explore various combinations of energy technologies and their quantitative and qualitative attributes that can satisfy the world's total primary energy supply (TPES) while making progress towards a near zero carbon future.

  19. Wolffian duct derivative anomalies: technical considerations when encountered during robot-assisted radical prostatectomy.

    PubMed

    Acharya, Sujeet S; Gundeti, Mohan S; Zagaja, Gregory P; Shalhav, Arieh L; Zorn, Kevin C

    2009-04-01

    Although malformations of the genitourinary tract are typically identified during childhood, they can remain silent until incidental detection in evaluation and treatment of other pathologies during adulthood. The advent of the minimally invasive era in urologic surgery has given rise to unique challenges in the surgical management of anomalies of the genitourinary tract. This article reviews the embryology of anomalies of Wolffian duct (WD) derivatives with specific attention to the seminal vesicles, vas deferens, ureter, and kidneys. This is followed by a discussion of the history of the laparoscopic approach to WD derivative anomalies. Finally, we present two cases to describe technical considerations when managing these anomalies when encountered during robotic-assisted radical prostatectomy. The University of Chicago Robotic Laparoscopic Radical Prostatectomy (RLRP) database was reviewed for cases where anomalies of WD derivatives were encountered. We describe how modifications in technique allowed for completion of the procedure without difficulty. None Of the 1230 RLRP procedures performed at our institution by three surgeons, only two cases (0.16%) have been noted to have a WD anomaly. These cases were able to be completed without difficulty by making simple modifications in technique. Although uncommon, it is important for the urologist to be familiar with the origin and surgical management of WD anomalies, particularly when detected incidentally during surgery. Simple modifications in technique allow for completion of RLRP without difficulty.

  20. Multivariate analyses applied to fetal, neonatal and pediatric MRI of neurodevelopmental disorders

    PubMed Central

    Levman, Jacob; Takahashi, Emi

    2015-01-01

    Multivariate analysis (MVA) is a class of statistical and pattern recognition methods that involve the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of medical neuroimaging-related challenges including identifying variables associated with a measure of clinical importance (i.e. patient outcome), creating diagnostic tests, assisting in characterizing developmental disorders, understanding disease etiology, development and progression, assisting in treatment monitoring and much more. Compared to adults, imaging of developing immature brains has attracted less attention from MVA researchers. However, remarkable MVA research growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to neurodevelopmental disorders in fetal, neonatal and pediatric magnetic resonance imaging (MRI) of the brain. The goal of this manuscript is to provide a concise review of the state of the scientific literature on studies employing brain MRI and MVA in a pre-adult population. Neurological developmental disorders addressed in the MVA research contained in this review include autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, schizophrenia and more. While the results of this review demonstrate considerable interest from the scientific community in applications of MVA technologies in pediatric/neonatal/fetal brain MRI, the field is still young and considerable research growth remains ahead of us. PMID:26640765

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