Development of insect resistant sunflowers: Updates and challenges

USDA-ARS?s Scientific Manuscript database

Entomology research of the sunflower research unit, USDA-ARS, in Fargo, ND, was discussed in a presentation to a group of producers, industry representatives, and scientists. There are 4 major insect pests for which we have no genetic resistance currently, and the goal of our work is to find genetic...

Cold Plasmas for Biofilm Control: Opportunities and Challenges.

PubMed

Gilmore, Brendan F; Flynn, Padrig B; O'Brien, Séamus; Hickok, Noreen; Freeman, Theresa; Bourke, Paula

2018-06-01

Bacterial biofilm infections account for a major proportion of chronic and medical device associated infections in humans, yet our ability to control them is compromised by their inherent tolerance to antimicrobial agents. Cold atmospheric plasma (CAP) represents a promising therapeutic option. CAP treatment of microbial biofilms represents the convergence of two complex phenomena: the production of a chemically diverse mixture of reactive species and intermediates, and their interaction with a heterogeneous 3D interface created by the biofilm extracellular polymeric matrix. Therefore, understanding these interactions and physiological responses to CAP exposure are central to effective management of infectious biofilms. We review the unique opportunities and challenges for translating CAP to the management of biofilms. Copyright © 2018. Published by Elsevier Ltd.

Engineering biological systems using automated biofoundries

PubMed Central

Chao, Ran; Mishra, Shekhar; Si, Tong; Zhao, Huimin

2017-01-01

Engineered biological systems such as genetic circuits and microbial cell factories have promised to solve many challenges in the modern society. However, the artisanal processes of research and development are slow, expensive, and inconsistent, representing a major obstacle in biotechnology and bioengineering. In recent years, biological foundries or biofoundries have been developed to automate design-build-test engineering cycles in an effort to accelerate these processes. This review summarizes the enabling technologies for such biofoundries as well as their early successes and remaining challenges. PMID:28602523

Management experiences and trends for water reuse implementation in Northern California.

PubMed

Bischel, Heather N; Simon, Gregory L; Frisby, Tammy M; Luthy, Richard G

2012-01-03

In 2010, California fell nearly 300,000 acre-ft per year (AFY) short of its goal to recycle 1,000,000 AFY of municipal wastewater. Growth of recycled water in the 48 Northern California counties represented only 20% of the statewide increase in reuse between 2001 and 2009. To evaluate these trends and experiences, major drivers and challenges that influenced the implementation of recycled water programs in Northern California are presented based on a survey of 71 program managers conducted in 2010. Regulatory requirements limiting discharge, cited by 65% of respondents as a driver for program implementation, historically played an important role in motivating many water reuse programs in the region. More recently, pressures from limited water supplies and needs for system reliability are prevalent drivers. Almost half of respondents (49%) cited ecological protection or enhancement goals as drivers for implementation. However, water reuse for direct benefit of natural systems and wildlife habitat represents just 6-7% of total recycling in Northern California and few financial incentives exist for such projects. Economic challenges are the greatest barrier to successful project implementation. In particular, high costs of distribution systems (pipelines) are especially challenging, with $1 to 3 million/mile costs experienced. Negative perceptions of water reuse were cited by only 26% of respondents as major hindrances to implementation of surveyed programs.

The Ties that Bind Us: Kymlicka on Culture and Education

ERIC Educational Resources Information Center

Pena-Rangel, David

2013-01-01

Most societies today are culturally diverse. Increasingly, minority groups are demanding recognition and self-governing rights to protect their ways of life against that of the majority. These demands represent a serious challenge for the state: how is it to balance between the equally legitimate claims of the many cultures inhabiting its…

Devil in the Details: Making Sensible Modifications to No Child Left Behind

ERIC Educational Resources Information Center

Ritter, Gary W.; Lucas, Christopher J.

2006-01-01

Achieving full compliance with the accountability provisions of the No Child Left Behind (NCLB) federal legislation poses major challenges for most of the nation's states. Structured, open-ended interviews were conducted with ranking representatives from a number of so-called high-readiness states: California, Florida, New York, South Carolina,…

Effects of Newcastle disease virus vaccine antibodies on the shedding and transmission of challenge viruses

USDA-ARS?s Scientific Manuscript database

Different genotypes of avian paramyxovirus serotype-1 virus (APMV-1) circulate in many parts of the world. Traditionally, Newcastle disease virus (NDV) is recognized as having two major divisions represented by class I and class II, with class II being further divided into eighteen genotypes. Alth...

Effects of Newcastle disease virus vaccine antibodies on the shedding and transmission of challenge viruses

USDA-ARS?s Scientific Manuscript database

Different genotypes of avian paramyxovirus serotype-1 virus (APMV-1) circulate in many parts of the world. Traditionally, Newcastle disease virus (NDV) is recognized as having two major divisions represented by class I and class II, with class II being further divided into sixteen genotypes. Althoug...

Temperature-sensitive, Post-translational Regulation of Plant Omega-3 Fatty-acid Desaturases is Mediated by the Endoplasmic Reticulum-associated Degradation Pathway

USDA-ARS?s Scientific Manuscript database

Changes in ambient temperature represent a major physiological challenge to poikilothermic organisms that requires rapid adjustments in the composition of cellular membranes in order to preserve overall membrane dynamics and integrity. In plants, the endoplasmic reticulum-localized omega-3 fatty ac...

Fine Arts Standards of Learning for Virginia Public Schools

ERIC Educational Resources Information Center

Virginia Department of Education, 2006

2006-01-01

The Fine Arts Standards of Learning in this publication represent a major development in public education in Virginia, emphasizing the importance of instruction in the fine arts (dance arts, music, theatre arts, and visual arts) as an important part of Virginia's efforts to provide challenging educational programs in the public schools. Knowledge…

Efficacy of type 2 PRRSV vaccine against Chinese and Vietnamese HP-PRRSV challenge in pigs

USDA-ARS?s Scientific Manuscript database

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant reproductive losses in the sow herd and respiratory disease in growing pigs. It is a virus that belongs to the family Arteriviridae virus for which there are two major genotypes, Type 1 represented by Lelystad virus, the ...

When Do Infants Begin to Follow a Point?

ERIC Educational Resources Information Center

Bertenthal, Bennett I.; Boyer, Ty W.; Harding, Samuel

2014-01-01

Infants' understanding of a pointing gesture represents a major milestone in their communicative development. The current consensus is that infants are not capable of following a pointing gesture until 9-12 months of age. In this article, we present evidence from 4- and 6-month-old infants challenging this conclusion. Infants were tested with…

The Market-Driven Age of Education: Challenges of Urban School Leadership

ERIC Educational Resources Information Center

May, Judy J.

2007-01-01

The school choice movement has become a major focus for traditional public school leaders. Facing declining student population and millions of dollars in lost funding, superintendents are now focused on the creation of effective market competition strategies. This represents not only a shift in thinking but adds another dimension to their…

Developing Leaders: The Role of Competencies in Rural Community Colleges

ERIC Educational Resources Information Center

Eddy, Pamela L.

2013-01-01

Pending retirements underscore the need to develop community college campus leaders. Rural community colleges will be particularly hard-hit by changes in leadership as they represent the majority of 2-year colleges and face unique challenges given their location. To help address the anticipated leadership transition, the American Association of…

Connectivity inference from neural recording data: Challenges, mathematical bases and research directions.

PubMed

Magrans de Abril, Ildefons; Yoshimoto, Junichiro; Doya, Kenji

2018-06-01

This article presents a review of computational methods for connectivity inference from neural activity data derived from multi-electrode recordings or fluorescence imaging. We first identify biophysical and technical challenges in connectivity inference along the data processing pipeline. We then review connectivity inference methods based on two major mathematical foundations, namely, descriptive model-free approaches and generative model-based approaches. We investigate representative studies in both categories and clarify which challenges have been addressed by which method. We further identify critical open issues and possible research directions. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Vaccines for HIV | NCI Technology Transfer Center | TTC

Cancer.gov

The development of an effective HIV vaccine has been an ongoing area of research. The high variability in HIV-1 virus strains has represented a major challenge in successful development. Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV. Two major hurdles to overcome are immunodominance and sequence diversity. This vaccine utilizes a strategy for overcoming these two issues by identifying the conserved regions of the virus and exploiting them for use in a targeted therapy. NCI seeks licensees and/or research collaborators to commercialize this technology, which has been validated in macaque models.

Fate of Trace Metals in Anaerobic Digestion.

PubMed

Fermoso, F G; van Hullebusch, E D; Guibaud, G; Collins, G; Svensson, B H; Carliell-Marquet, C; Vink, J P M; Esposito, G; Frunzo, L

2015-01-01

A challenging, and largely uncharted, area of research in the field of anaerobic digestion science and technology is in understanding the roles of trace metals in enabling biogas production. This is a major knowledge gap and a multifaceted problem involving metal chemistry; physical interactions of metal and solids; microbiology; and technology optimization. Moreover, the fate of trace metals, and the chemical speciation and transport of trace metals in environments--often agricultural lands receiving discharge waters from anaerobic digestion processes--simultaneously represents challenges for environmental protection and opportunities to close process loops in anaerobic digestion.

Adaptive Design of Confirmatory Trials: Advances and Challenges

PubMed Central

Lai, Tze Leung; Lavori, Philip W.; Tsang, Ka Wai

2015-01-01

The past decade witnessed major developments in innovative designs of confirmatory clinical trials, and adaptive designs represent the most active area of these developments. We give an overview of the developments and associated statistical methods in several classes of adaptive designs of confirmatory trials. We also discuss their statistical difficulties and implementation challenges, and show how these problems are connected to other branches of mainstream Statistics, which we then apply to resolve the difficulties and bypass the bottlenecks in the development of adaptive designs for the next decade. PMID:26079372

Challenging the paradigms of deep-sea ecology.

PubMed

Danovaro, Roberto; Snelgrove, Paul V R; Tyler, Paul

2014-08-01

Deep-sea ecosystems represent Earth's major ecological research frontier. Focusing on seafloor ecosystems, we demonstrate how new technologies underpin discoveries that challenge major ecological hypotheses and paradigms, illuminating new deep-sea geosphere-biosphere interactions. We now recognize greater habitat complexity, new ecological interactions and the importance of 'dark energy', and chemosynthetic production in fuelling biodiversity. We also acknowledge functional hotspots that contradict a food-poor, metabolically inactive, and minor component of global carbon cycles. Symbioses appear widespread, revealing novel adaptations. Populations show complex spatial structure and evolutionary histories. These new findings redefine deep-sea ecology and the role of Earth's largest biome in global biosphere functioning. Indeed, deep-sea exploration can open new perspectives in ecological research to help mitigate exploitation impacts. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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

Impact and Challenge R&D in the FY 1983 Budget. Colloquium Proceedings (Washington, D.C. June 23-24, 1982).

ERIC Educational Resources Information Center

Teich, Albert H., Ed.; Weinberg, Jill P., Ed.

Provided are papers and speeches presented at the Seventh Annual American Association for the Advancement of Science (AAAS) Colloquium on Research and Development (R&D) Policy. Presenters included key representatives of Congress, the Reagan administration, government agencies, and those involved in industry and university R&D. Major areas…

Tribal wilderness research needs and issues in the United States and Canada

Treesearch

Dan McDonald; Tom McDonald; Leo H. McAvoy

2000-01-01

This paper represents a dialogue between tribal wilderness managers and researchers on the primary research needs of tribal wilderness in the United States and Canada. The authors identify a number of research priorities for tribal wildlands. The paper also discusses some major issues and challenges faced by researchers conducting research in areas that are culturally...

Schools for the Twenty-First Century: School Design and Educational Transformation

ERIC Educational Resources Information Center

Leiringer, Roine; Cardellino, Paula

2011-01-01

The Building Schools for the Future programme has been established to ensure that English secondary schools are designed or redesigned to allow for educational transformation. The programme represents the biggest single UK government investment in school buildings for over 50 years. For this reason, it poses a major challenge to those involved in…

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

Matthiesen, John; Hoff, Thomas; Liu, Chi

The production of chemicals from lignocellulosic biomass provides opportunities to synthesize chemicals with new functionalities and grow a more sustainable chemical industry. However, new challenges emerge as research transitions from petrochemistry to biorenewable chemistry. Compared to petrochemisty, the selective conversion of biomass-derived carbohydrates requires most catalytic reactions to take place at low temperatures (< 300°C) and in the condensed phase to prevent reactants and products from degrading. The stability of heterogeneous catalysts in liquid water above the normal boiling point represents one of the major challenges to overcome. Herein, we review some of the latest advances in the field withmore » an emphasis on the role of carbon materials and carbon nanohybrids in addressing this challenge.« less

Alarums false, alarums real: challenges and threats to the future of epidemiology.

PubMed

Bracken, M B

1998-02-01

A review of recent threats and challenges to epidemiology suggests that some represent an opportunity to advance the discipline while others are a major threat to conducting epidemiologic work. Two issues are identified which should advance the publication and conduct of epidemiologic research. Three are discussed that exemplify current threats. Epidemiologists have a role in helping journalists improve the communication of risk information in the media. Methodological advances for studies of rare exposure being related to rare disease should reduce the frequency of conflicting results in the epidemiologic literature. Three significant external forces that threaten epidemiologic research are identified. These are: unbridled discovery during litigation as exemplified by Bendectin, breast implants and cellular telephones; over zealous privacy laws; and the negative impact of managed care on epidemiologic research. The American College of Epidemiology has a major role to play in protecting the profession from some of the real threats that face it, and in helping meet the challenges.

Gendered Pathways: How Mathematics Ability Beliefs Shape Secondary and Postsecondary Course and Degree Field Choices

PubMed Central

Perez-Felkner, Lara; Nix, Samantha; Thomas, Kirby

2017-01-01

Do mathematics ability beliefs explain gender gaps in the physical science, engineering, mathematics, and computer science fields (PEMC) and other science fields? We leverage U.S. nationally representative longitudinal data to estimate gendered differences in girls' and boys' perceptions of mathematics ability with the most difficult or challenging material. Our analyses examine the potentially interacting effects of gender and these ability beliefs on students' pathways to scientific careers. Specifically, we study how beliefs about ability with challenging mathematics influence girls' and boys' choices to pursue PEMC degrees, evaluating educational milestones over a 6-year period: advanced science course completion in secondary school and postsecondary major retention and selection. Our findings indicate even at the same levels of observed ability, girls' mathematics ability beliefs under challenge are markedly lower than those of boys. These beliefs matter over time, potentially tripling girls' chances of majoring in PEMC sciences, over and above biological science fields, all else being equal. Implications and potential interventions are discussed. PMID:28428762

Gendered Pathways: How Mathematics Ability Beliefs Shape Secondary and Postsecondary Course and Degree Field Choices.

PubMed

Perez-Felkner, Lara; Nix, Samantha; Thomas, Kirby

2017-01-01

Do mathematics ability beliefs explain gender gaps in the physical science, engineering, mathematics, and computer science fields (PEMC) and other science fields? We leverage U.S. nationally representative longitudinal data to estimate gendered differences in girls' and boys' perceptions of mathematics ability with the most difficult or challenging material. Our analyses examine the potentially interacting effects of gender and these ability beliefs on students' pathways to scientific careers. Specifically, we study how beliefs about ability with challenging mathematics influence girls' and boys' choices to pursue PEMC degrees, evaluating educational milestones over a 6-year period: advanced science course completion in secondary school and postsecondary major retention and selection. Our findings indicate even at the same levels of observed ability, girls' mathematics ability beliefs under challenge are markedly lower than those of boys. These beliefs matter over time, potentially tripling girls' chances of majoring in PEMC sciences, over and above biological science fields, all else being equal. Implications and potential interventions are discussed.

Six Challenges for Ethical Conduct in Science.

PubMed

Niemi, Petteri

2016-08-01

The realities of human agency and decision making pose serious challenges for research ethics. This article explores six major challenges that require more attention in the ethics education of students and scientists and in the research on ethical conduct in science. The first of them is the routinization of action, which makes the detection of ethical issues difficult. The social governance of action creates ethical problems related to power. The heuristic nature of human decision making implies the risk of ethical bias. The moral disengagement mechanisms represent a human tendency to evade personal responsibility. The greatest challenge of all might be the situational variation in people's ethical behaviour. Even minor situational factors have a surprisingly strong influence on our actions. Furthermore, finally, the nature of ethics itself also causes problems: instead of clear answers, we receive a multitude of theories and intuitions that may sometimes be contradictory. All these features of action and ethics represent significant risks for ethical conduct in science. I claim that they have to be managed within the everyday practices of science and addressed explicitly in research ethics education. I analyse them and suggest some ways in which their risks can be alleviated.

Implementing quality initiatives in healthcare organizations: drivers and challenges.

PubMed

Abdallah, Abdallah

2014-01-01

Various quality initiatives seem to have successful implementation in some healthcare organizations yet fail in others. This paper sets out to study the literature trying to understand drivers and challenges facing quality initiatives implementation in healthcare organizations then compare findings from literature with those of a structured questionnaire answered by 60 representatives from 18 hospitals. Finally it proposes a framework that mitigates challenges and utilizes drivers to ensure best implementation results. Literature regarding implementing various quality initiatives in the healthcare sector was reviewed. Representatives from several healthcare organizations were surveyed. Results from both approaches are compared to highlight the key challenges and drivers facing implementers. This research reveals that internal factors related to leadership and employees greatly affect quality initiative success or failure. Design and relevance play a major role in successful implementation. PRACTICAL IMPLICATIONs: This research offers healthcare professionals greater success when implementing certain quality initiatives by taking success/failure factors into consideration. A general framework for successful implementation in the healthcare sector is provided. This article uncovers reasons behind success or failure in a comprehensive and practical way. It also explores how most popular quality initiatives are applied in hospitals.

Decellularized material as scaffolds for tissue engineering studies in long gap esophageal atresia.

PubMed

Lee, Esmond; Milan, Anna; Urbani, Luca; De Coppi, Paolo; Lowdell, Mark W

2017-05-01

Esophageal atresia refers to an anomaly in foetal development in which the esophagus terminates in a blind end. Whilst surgical correction is achievable in most patients, when a long gap is present it still represents a major challenge associated with higher morbidity and mortality. In this context, tissue engineering could represent a successful alternative to restore oesophageal function and structure. Naturally derived biomaterials made of decellularized tissues retain native extracellular matrix architecture and composition, providing a suitable bed for the anchorage and growth of relevant cell types. Areas covered: This review outlines the various strategies and challenges in esophageal tissue engineering, highlighting the evolution of ideas in the development of decellularized scaffolds for clinical use. It explores the interplay between clinical needs, ethical dilemmas, and manufacturing challenges in the development of a tissue engineered decellularized scaffold for oesophageal atresia. Expert opinion: Current progress on oesophageal tissue engineering has enabled effective repair of patch defects, whilst the development of a full circumferential construct remains a challenge. Despite the different approaches available and the improvements achieved, a gold standard for fully functional tissue engineered oesophageal constructs has not been defined yet.

Cross-border-assisted reproduction: a qualitative account of UK travellers' experiences.

PubMed

Hudson, Nicky; Culley, Lorraine; Blyth, Eric; Norton, Wendy; Pacey, Allan; Rapport, Frances

2016-06-01

Surveys on patients' experiences of cross-border fertility treatment have reported a range of positive and challenging features. However, the number of such studies is limited, and there is no detailed qualitative account of the experiences of UK patients who travel overseas for fertility treatment. The present study used a cross-sectional, qualitative design and in-depth interviews. Fifty-one participants (41 women and 10 men, representing 41 treatment 'cases') participated in semi-structured interviews. The experiences reported were broadly positive with a large proportion of participants (39 cases, 95%) citing a favourable overall experience with only two cases (5%) reporting a more negative experience. Thematic analysis revealed 6 major categories and 20 sub-categories, which described the positive and challenging aspects of cross-border fertility travel. The positive aspects were represented by the categories: 'access', 'control' and 'care and respect'. The more challenging aspects were categorized as 'logistics and coordination of care', 'uncertainty' and 'cultural dissonance'. The study confirms findings from others that despite some challenges, there is a relatively high level of patient satisfaction with cross-border treatment with participants able to extend the boundaries of their fertility-seeking trajectories and in some cases, regain a sense of control over their treatment.

Exploring bacterial lignin degradation.

PubMed

Brown, Margaret E; Chang, Michelle C Y

2014-04-01

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

Engineering biological systems using automated biofoundries.

PubMed

Chao, Ran; Mishra, Shekhar; Si, Tong; Zhao, Huimin

2017-07-01

Engineered biological systems such as genetic circuits and microbial cell factories have promised to solve many challenges in the modern society. However, the artisanal processes of research and development are slow, expensive, and inconsistent, representing a major obstacle in biotechnology and bioengineering. In recent years, biological foundries or biofoundries have been developed to automate design-build-test engineering cycles in an effort to accelerate these processes. This review summarizes the enabling technologies for such biofoundries as well as their early successes and remaining challenges. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

The significance of major and stable molecular responses in chronic myeloid leukemia in the tyrosine kinase inhibitor era

PubMed Central

Renault, Ilana Zalcberg; Scholl, Vanesa; Hassan, Rocio; Capelleti, Paola; de Lima, Marcos; Cortes, Jorge

2011-01-01

Tyrosine kinase inhibitors have changed the management and outcomes of chronic myeloid leukemia patients. Quantitative polymerase chain reaction is used to monitor molecular responses to tyrosine kinase inhibitors. Molecular monitoring represents the most sensitive tool to judge chronic myeloid leukemia disease course and allows early detection of relapse. Evidence of achieving molecular response is important for several reasons: 1. early molecular response is associated with major molecular response rates at 18-24 months; 2. patients achieving major molecular response are less likely to lose their complete cytogenetic response; 3. a durable, stable major molecular response is associated with increased progression-free survival. However, standardization of molecular techniques is still challenging. PMID:23049363

Neurodevelopmental surveillance in the first 2 years after extremely preterm birth: evidence, challenges, and guidelines.

PubMed

Msall, Michael E

2006-03-01

During the past decade, major advances in maternal-fetal medicine and neonatology have resulted in unprecedented survival of very preterm babies. These babies represent a small fraction of infants born preterm, but present significant challenges with respect to respiratory, nutritional, and developmental vulnerabilities. Several efforts involving the UK, US, Canada, Australia, and the Netherlands have provided information on regional trends over time with respect to neonatal morbidities and neurodevelopmental outcomes through the first two years of life. Historically gross and fine motor, cognitive and communicative skills, vision and hearing performance have been the focus of assessment. Indicators of major neurodevelopmental disabilities at 2 years have included presence of severe neurosensory impairment, i.e. cerebral palsy, sensorineural hearing loss requiring aides, and blindness. In addition cognitive developmental disability has been generally defined as a Bayley MDI or developmental quotient <70, i.e. lower than 2 standard deviations below the mean. However these outcomes cannot reliably capture trajectories of resiliency as well as more complex developmental challenges in the domains of coordination, perception, attention, communication, and learning. Recently tools have become available for assessing functional status in gross motor, communicative, adaptive and social-emotional behaviours of imitation, regulation, and play. This review will describe the major progress in assessing early neurodevelopmental status of vulnerable survivors receiving new biomedical technologies, highlight challenges, and propose guidelines based on current best evidence.

Radio frequency analog electronics based on carbon nanotube transistors

PubMed Central

Kocabas, Coskun; Kim, Hoon-sik; Banks, Tony; Rogers, John A.; Pesetski, Aaron A.; Baumgardner, James E.; Krishnaswamy, S. V.; Zhang, Hong

2008-01-01

The potential to exploit single-walled carbon nanotubes (SWNTs) in advanced electronics represents a continuing, major source of interest in these materials. However, scalable integration of SWNTs into circuits is challenging because of difficulties in controlling the geometries, spatial positions, and electronic properties of individual tubes. We have implemented solutions to some of these challenges to yield radio frequency (RF) SWNT analog electronic devices, such as narrow band amplifiers operating in the VHF frequency band with power gains as high as 14 dB. As a demonstration, we fabricated nanotube transistor radios, in which SWNT devices provide all of the key functions, including resonant antennas, fixed RF amplifiers, RF mixers, and audio amplifiers. These results represent important first steps to practical implementation of SWNTs in high-speed analog circuits. Comparison studies indicate certain performance advantages over silicon and capabilities that complement those in existing compound semiconductor technologies. PMID:18227509

Meeting current and future conservation challenges through the synthesis of long-term silviculture and range management research

Treesearch

Mary Beth Adams; Joe NcNeel

2010-01-01

The Experimental Forests and Ranges (EFRs) of the Forest Service, U.S. Department of Agriculture were established to represent major forest vegetation types of the United States, to provide guidelines for management of those forests and ranges, and to serve as "outdoor classrooms" for land managers to learn how to better manage their forests. Research data...

Prosthetic Joint Infections

PubMed Central

Aslam, Saima; Darouiche, Rabih O.

2012-01-01

Prosthetic joint infections represent a major therapeutic challenge for both healthcare providers and patients. This paper reviews the predisposing factors, pathogenesis, microbiology, diagnosis, treatment and prophylaxis of prosthetic joint infection. The most optimal management strategy should be identified based on a number of considerations including type and duration of infection, antimicrobial susceptibility of the infecting pathogen, condition of infected tissues and bone stock, patient wishes and functional status. PMID:22847032

Stocktype and grass suppression accelerate the restoration trajectory of Acacia koa in Hawaiian montane ecosystems

Treesearch

Jeremy Pinto; Anthony S. Davis; James J. K. Leary; Matthew M. Aghai

2015-01-01

Restoring degraded mesic-montane forests represents a major challenge in maintaining functioning ecosystems throughout the tropics. A key example of this lies in Hawai‘i, where restoring native koa (Acacia koa, A. Gray) forests are a top conservation and forestry priority because of the critical habitat and high-value timber products that they provide. Efforts...

Present capabilities and future requirements for computer-aided geometric modeling in the design and manufacture of gas turbine

NASA Technical Reports Server (NTRS)

Caille, E.; Propen, M.; Hoffman, A.

1984-01-01

Gas turbine engine design requires the ability to rapidly develop complex structures which are subject to severe thermal and mechanical operating loads. As in all facets of the aerospace industry, engine designs are constantly driving towards increased performance, higher temperatures, higher speeds, and lower weight. The ability to address such requirements in a relatively short time frame has resulted in a major thrust towards integrated design/analysis/manufacturing systems. These computer driven graphics systems represent a unique challenge, with major payback opportunities if properly conceived, implemented, and applied.

Collision Avoidance Short Course Part I: Theory

NASA Technical Reports Server (NTRS)

Hejduk, Matthew D.

2017-01-01

Satellite conjunction assessment is perhaps the fastest-growing area in space situational awareness and protection, with military, civil, and commercial satellite owner operators embracing more and more sophisticated processes to avoid the avoidable namely collisions between high-value space assets and orbital debris. NASA and CNES have collaborated to offer an introductory short course on all the major aspects of the conjunction assessment problem. This half-day course will cover satellite conjunction dynamics and theory, JSpOC conjunction data products, major risk assessment parameters and plots, conjunction remediation decision support, and present and future challenges. This briefing represents the NASA portion of the course.

Beam Stability R&D for the APS MBA Upgrade

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

Sereno, Nicholas S.; Arnold, Ned D.; Bui, Hanh D.

2015-01-01

Beam diagnostics required for the APS Multi-bend acromat (MBA) are driven by ambitious beam stability requirements. The major AC stability challenge is to correct rms beam motion to 10% the rms beam size at the insertion device source points from0.01 to 1000 Hz. The vertical plane represents the biggest challenge forAC stability, which is required to be 400 nm rms for a 4-micron vertical beam size. In addition to AC stability, long-term drift over a period of seven days is required to be 1 micron or less. Major diagnostics R&D components include improved rf beam position processing using commercially availablemore » FPGA-based BPM processors, new X-ray beam position monitors based on hard X-ray fluorescence from copper and Compton scattering off diamond, mechanical motion sensing to detect and correct long-term vacuum chamber drift, a new feedback system featuring a tenfold increase in sampling rate, and a several-fold increase in the number of fast correctors and BPMs in the feedback algorithm. Feedback system development represents a major effort, and we are pursuing development of a novel algorithm that integrates orbit correction for both slow and fast correctors down to DC simultaneously. Finally, a new data acquisition system (DAQ) is being developed to simultaneously acquire streaming data from all diagnostics as well as the feedback processors for commissioning and fault diagnosis. Results of studies and the design effort are reported.« less

D3R Grand Challenge 2: blind prediction of protein-ligand poses, affinity rankings, and relative binding free energies

NASA Astrophysics Data System (ADS)

Gaieb, Zied; Liu, Shuai; Gathiaka, Symon; Chiu, Michael; Yang, Huanwang; Shao, Chenghua; Feher, Victoria A.; Walters, W. Patrick; Kuhn, Bernd; Rudolph, Markus G.; Burley, Stephen K.; Gilson, Michael K.; Amaro, Rommie E.

2018-01-01

The Drug Design Data Resource (D3R) ran Grand Challenge 2 (GC2) from September 2016 through February 2017. This challenge was based on a dataset of structures and affinities for the nuclear receptor farnesoid X receptor (FXR), contributed by F. Hoffmann-La Roche. The dataset contained 102 IC50 values, spanning six orders of magnitude, and 36 high-resolution co-crystal structures with representatives of four major ligand classes. Strong global participation was evident, with 49 participants submitting 262 prediction submission packages in total. Procedurally, GC2 mimicked Grand Challenge 2015 (GC2015), with a Stage 1 subchallenge testing ligand pose prediction methods and ranking and scoring methods, and a Stage 2 subchallenge testing only ligand ranking and scoring methods after the release of all blinded co-crystal structures. Two smaller curated sets of 18 and 15 ligands were developed to test alchemical free energy methods. This overview summarizes all aspects of GC2, including the dataset details, challenge procedures, and participant results. We also consider implications for progress in the field, while highlighting methodological areas that merit continued development. Similar to GC2015, the outcome of GC2 underscores the pressing need for methods development in pose prediction, particularly for ligand scaffolds not currently represented in the Protein Data Bank (http://www.pdb.org), and in affinity ranking and scoring of bound ligands.

Dynamic Bayesian network modeling for longitudinal brain morphometry

PubMed Central

Chen, Rong; Resnick, Susan M; Davatzikos, Christos; Herskovits, Edward H

2011-01-01

Identifying interactions among brain regions from structural magnetic-resonance images presents one of the major challenges in computational neuroanatomy. We propose a Bayesian data-mining approach to the detection of longitudinal morphological changes in the human brain. Our method uses a dynamic Bayesian network to represent evolving inter-regional dependencies. The major advantage of dynamic Bayesian network modeling is that it can represent complicated interactions among temporal processes. We validated our approach by analyzing a simulated atrophy study, and found that this approach requires only a small number of samples to detect the ground-truth temporal model. We further applied dynamic Bayesian network modeling to a longitudinal study of normal aging and mild cognitive impairment — the Baltimore Longitudinal Study of Aging. We found that interactions among regional volume-change rates for the mild cognitive impairment group are different from those for the normal-aging group. PMID:21963916

Lignin conversion: Opportunities and challenges for the integrated biorefinery

DOE PAGES

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

2016-06-21

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

Lignin conversion: Opportunities and challenges for the integrated biorefinery

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

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

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

[Health care economic guidance in Germany from the example Morbi-RSA].

PubMed

Litmathe, Jens

2016-04-01

Increasing costs in health care represent still a major challenge in most industrial contries. A lot of attempts especially in Germany have been made to manage such problems and for a fair allocation oft he underlying resources. One of this ist the Morbi-RSA. The current review reflects all historical, medical and economical aspects of the Morbi-RSA and gives a perspective to possible future developments.

A Systems Analysis and Design Case Study for a Business Modeling Learning Experience for a Capstone CIS/IS Systems Development Class

ERIC Educational Resources Information Center

Russell, Jack; Russell, Barbara

2015-01-01

The goal is to provide a robust and challenging problem statement for a capstone, advanced systems analysis and design course for CIS/MIS/CS majors. In addition to the problem narrative, a representative solution for much of the business modeling deliverables is presented using the UML paradigm. A structured analysis deliverable will be the topic…

The role of EEPROM devices in upcoming ISDN applications

NASA Astrophysics Data System (ADS)

Nette, Herbert L.

1991-02-01

Integrated Services Digital Network (ISDN) equipments are rapidly becoming a major market for semiconductor chips. Although at first glance this growing market appears to be geared at logic chips, nonvolatile memories represent important support chips and will become a significant segment of this market. Challenges in these applications consist in operating EEPROMs at lower voltages and lower power and embedding them on ever more complex communications processor chips.

Harmonisation of Global Land-Use Scenarios for the Period 1500-2100 for IPCC-AR5

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

Hurtt, George; Chini, Louise Parsons; Frolking, Steve

2009-06-01

In preparation for the fifth Intergovernmental Panel on Climate Change climate change assessment (IPCC-AR5), the international community is developing new advanced computer models (CMs) to address the combined effects of human activities (e.g. land-use and fossil fuel emissions) on the carbon-climate system. In addition, four Representative Concentration Pathway (RCP) scenarios of the future (2005-2100) are being developed by four Integrated Assessment Modeling teams (IAMs) to be used as input to the CMs for future climate projections. The diversity of requirements and approaches among CMs and IAMs for tracking land-use changes (past, present, and future), presents major challenges for treating land-usemore » comprehensively and consistently between these communities. As part of an international working group, we have been working to meet these challenges by developing a "harmonized" set of land-use change scenarios that smoothly connects gridded historical reconstructions of land-use with future projections, in a format required by CMs. This approach to harmonizing the treatment of land-use between two key modeling communities, CMs and IAMs, represents a major advance that will facilitate more consistent and fuller treatments of land-use/land-use change effects including both CO2 emissions and corresponding land-surface changes.« less

Scaling uncertainties in estimating canopy foliar maintenance respiration for black spruce ecosystems in Alaska

USGS Publications Warehouse

Zhang, X.; McGuire, A.D.; Ruess, Roger W.

2006-01-01

A major challenge confronting the scientific community is to understand both patterns of and controls over spatial and temporal variability of carbon exchange between boreal forest ecosystems and the atmosphere. An understanding of the sources of variability of carbon processes at fine scales and how these contribute to uncertainties in estimating carbon fluxes is relevant to representing these processes at coarse scales. To explore some of the challenges and uncertainties in estimating carbon fluxes at fine to coarse scales, we conducted a modeling analysis of canopy foliar maintenance respiration for black spruce ecosystems of Alaska by scaling empirical hourly models of foliar maintenance respiration (Rm) to estimate canopy foliar Rm for individual stands. We used variation in foliar N concentration among stands to develop hourly stand-specific models and then developed an hourly pooled model. An uncertainty analysis identified that the most important parameter affecting estimates of canopy foliar Rm was one that describes R m at 0??C per g N, which explained more than 55% of variance in annual estimates of canopy foliar Rm. The comparison of simulated annual canopy foliar Rm identified significant differences between stand-specific and pooled models for each stand. This result indicates that control over foliar N concentration should be considered in models that estimate canopy foliar Rm of black spruce stands across the landscape. In this study, we also temporally scaled the hourly stand-level models to estimate canopy foliar Rm of black spruce stands using mean monthly temperature data. Comparisons of monthly Rm between the hourly and monthly versions of the models indicated that there was very little difference between the estimates of hourly and monthly models, suggesting that hourly models can be aggregated to use monthly input data with little loss of precision. We conclude that uncertainties in the use of a coarse-scale model for estimating canopy foliar Rm at regional scales depend on uncertainties in representing needle-level respiration and on uncertainties in representing the spatial variability of canopy foliar N across a region. The development of spatial data sets of canopy foliar N represents a major challenge in estimating canopy foliar maintenance respiration at regional scales. ?? Springer 2006.

Identification of Challenges to the Availability and Accessibility of Opioids in Twelve European Countries: Conclusions from Two ATOME Six-Country Workshops.

PubMed

Linge-Dahl, Lisa; Vranken, Marjolein; Juenger, Saskia; North, Kate; Scholten, Willem; Payne, Sheila; Radbruch, Lukas

2015-12-01

Access to many controlled medicines is inadequate in a number of European countries. This leads to deficits in the treatment of moderate to severe pain as well as in opioid agonist therapy. The study objective was to elaborate the reasons for this inadequacy. The work plan of the Access to Opioid Medication in Europe (ATOME) project included two six-country workshops. These workshops comprised a national situational analysis, drafting tailor-made recommendations for improvement and developing action plans for their implementation. In total, 84 representatives of the national Ministries of Health, national controlled substances authorities, experts representing regulatory and law enforcement authorities, leading health care professionals, and patient representatives from 13 European countries participated in either one of the workshops. The delegates used breakout sessions to identify key common challenges. Content analysis was used for the evaluation of protocols and field notes. A number of challenges to opioid accessibility in the countries was identified in the domains of knowledge and educational, regulatory, legislative, as well as public awareness and training barriers that limit opioid prescription. In addition, short validity of prescriptions and bureaucratic practices resulting in overregulation impeded availability of some essential medicines. Stigmatization and criminalisation of people who use drugs remained the major impediment to increasing opioid agonist program coverage. The challenges identified during outcomes of the workshops were used as the basis for subsequent dissemination and implementation activities in the ATOME project, and in some countries the workshop proceedings already served as a stepping-stone for the first changes in regulations and legislation.

RIVER CORRIDOR BUILDINGS 324 & 327 CLEANUP

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

BAZZELL, K.D.; SMITH, B.A.

2006-02-09

A major challenge in the recently awarded River Corridor Closure (RCC) Contract at the U.S. Department of Energy's (DOE) Hanford Site is decontaminating and demolishing (D&D) facilities in the 300 Area. Located along the banks of the Columbia River about one mile north of Richland, Washington, the 2.5 km{sup 2} (1 mi{sup 2})300 Area comprises only a small part of the 1517 km{sup 2} (586 mi{sup 2}) Hanford Site. However, with more than 300 facilities ranging from clean to highly contaminated, D&D of those facilities represents a major challenge for Washington Closure Hanford (WCH), which manages the new RCC Projectmore » for DOE's Richland Operations Office (RL). A complicating factor for this work is the continued use of nearly a dozen facilities by the DOE's Pacific Northwest National Laboratory (PNNL). Most of the buildings will not be released to WCH until at least 2009--four years into the seven-year, $1.9 billion RCC Contract. The challenge will be to deactivate, decommission, decontaminate and demolish (D4) highly contaminated buildings, such as 324 and 327, without interrupting PNNL's operations in adjacent facilities. This paper focuses on the challenges associated with the D4 of the 324 Building and the 327 Building.« less

Challenges in leveraging existing human performance data for quantifying the IDHEAS HRA method

DOE PAGES

Liao, Huafei N.; Groth, Katrina; Stevens-Adams, Susan

2015-07-29

Our article documents an exploratory study for collecting and using human performance data to inform human error probability (HEP) estimates for a new human reliability analysis (HRA) method, the IntegrateD Human Event Analysis System (IDHEAS). The method was based on cognitive models and mechanisms underlying human behaviour and employs a framework of 14 crew failure modes (CFMs) to represent human failures typical for human performance in nuclear power plant (NPP) internal, at-power events [1]. A decision tree (DT) was constructed for each CFM to assess the probability of the CFM occurring in different contexts. Data needs for IDHEAS quantification aremore » discussed. Then, the data collection framework and process is described and how the collected data were used to inform HEP estimation is illustrated with two examples. Next, five major technical challenges are identified for leveraging human performance data for IDHEAS quantification. Furthermore, these challenges reflect the data needs specific to IDHEAS. More importantly, they also represent the general issues with current human performance data and can provide insight for a path forward to support HRA data collection, use, and exchange for HRA method development, implementation, and validation.« less

Collision Avoidance "Short Course" Part III: CA Role in Changing Space Flight Environment

NASA Technical Reports Server (NTRS)

Newman, Lauri

2017-01-01

Satellite conjunction assessment is perhaps the fastest-growing area in space situational awareness and protection, with military, civil, and commercial satellite owner operators embracing more and more sophisticated processes to avoid the avoidable namely collisions between high-value space assets and orbital debris. NASA and CNES have collaborated to offer an introductory short course on all the major aspects of the conjunction assessment problem. This half-day course will cover satellite conjunction dynamics and theory, JSpOC conjunction data products, major risk assessment parameters and plots, conjunction remediation decision support, and present and future challenges. This briefing represents the NASA portion of the course.

Department of Labor. Challenges in Ensuring Workforce Development and Worker Protection. Testimony before the Subcommittee on Human Resources, Committee on Government Reform and Oversight, House of Representatives.

ERIC Educational Resources Information Center

Joyner, Carlotta C.

In Fiscal Year 1997, the U.S. Department of Labor (DOL) has an estimated budget of $34.4 billion and is authorized 16,614 full-time-equivalent staff-years. DOL's many programs fall into two major categories: enhancing workers' skills through job training and ensuring worker protection. The DOL's work force development mission is being challenged…

Tumor Heterogeneity, Single-Cell Sequencing, and Drug Resistance.

PubMed

Schmidt, Felix; Efferth, Thomas

2016-06-16

Tumor heterogeneity has been compared with Darwinian evolution and survival of the fittest. The evolutionary ecosystem of tumors consisting of heterogeneous tumor cell populations represents a considerable challenge to tumor therapy, since all genetically and phenotypically different subpopulations have to be efficiently killed by therapy. Otherwise, even small surviving subpopulations may cause repopulation and refractory tumors. Single-cell sequencing allows for a better understanding of the genomic principles of tumor heterogeneity and represents the basis for more successful tumor treatments. The isolation and sequencing of single tumor cells still represents a considerable technical challenge and consists of three major steps: (1) single cell isolation (e.g., by laser-capture microdissection), fluorescence-activated cell sorting, micromanipulation, whole genome amplification (e.g., with the help of Phi29 DNA polymerase), and transcriptome-wide next generation sequencing technologies (e.g., 454 pyrosequencing, Illumina sequencing, and other systems). Data demonstrating the feasibility of single-cell sequencing for monitoring the emergence of drug-resistant cell clones in patient samples are discussed herein. It is envisioned that single-cell sequencing will be a valuable asset to assist the design of regimens for personalized tumor therapies based on tumor subpopulation-specific genetic alterations in individual patients.

Developing a new syndromic surveillance system for the London 2012 Olympic and Paralympic Games.

PubMed

Harcourt, S E; Fletcher, J; Loveridge, P; Bains, A; Morbey, R; Yeates, A; McCloskey, B; Smyth, B; Ibbotson, S; Smith, G E; Elliot, A J

2012-12-01

Syndromic surveillance is vital for monitoring public health during mass gatherings. The London 2012 Olympic and Paralympic Games represents a major challenge to health protection services and community surveillance. In response to this challenge the Health Protection Agency has developed a new syndromic surveillance system that monitors daily general practitioner out-of-hours and unscheduled care attendances. This new national system will fill a gap identified in the existing general practice-based syndromic surveillance systems by providing surveillance capability of general practice activity during evenings/nights, over weekends and public holidays. The system will complement and supplement the existing tele-health phone line, general practitioner and emergency department syndromic surveillance systems. This new national system will contribute to improving public health reassurance, especially to meet the challenges of the London 2012 Olympic and Paralympic Games.

Hydrogen storage and fuel cells

NASA Astrophysics Data System (ADS)

Liu, Di-Jia

2018-01-01

Global warming and future energy supply are two major challenges facing American public today. To overcome such challenges, it is imperative to maximize the existing fuel utilization with new conversion technologies while exploring alternative energy sources with minimal environmental impact. Hydrogen fuel cell represents a next-generation energy-efficient technology in transportation and stationary power productions. In this presentation, a brief overview of the current technology status of on-board hydrogen storage and polymer electrolyte membrane fuel cell in transportation will be provided. The directions of the future researches in these technological fields, including a recent "big idea" of "H2@Scale" currently developed at the U. S. Department of Energy, will also be discussed.

Giant fibrosarcoma prostuberans of abodominal wall: management problems in resources-constrained country.

PubMed

Chukwuanukwu, T O G; Anyanwu, S N C

2009-09-01

Abdominal wall sarcomas represent less than 1% of adult malignancies. Dermatofibrosarcoma protuberans can grow to very large sizes and the recommended resection 2-3 cm from the macroscopic tumour margin can produce very large full thickness defects of the abdominal wall. Reconstruction of such defects can be quite challenging in resource constrained areas where patients present late with giant lesions. To highlight the presentation and management challenges faced by the surgical oncologist and reconstructive surgeon in a resource constrained country when faced with giant Dermatofibrosarcoma protuberans of the abdominal wall. Prospective study of patients with abdominal wall soft tissue sarcoma presenting to the authors. Cases of giant dermatofibrosarcoma protuberns who underwent surgery were analysed. Seven cases managed over an eight year period (January 2000 to December 2007). Age ranged from 27-70 yrs with slight female preponderance 1.5:1 F:M. Three presented with recurrent fungating masses. Only one could be reconstructed with prolene mesh. One recurrence was noted during the period under study. Poverty, ignorance and lack of necessary working tools are major challenges faced by the surgical oncologist and reconstructive surgeon in resource constrained areas and pose a major obstacle to the control of cancer in these areas.

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

PubMed

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

2007-12-01

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

Characterization of the conformational equilibrium between the two major substates of RNase A using NMR chemical shifts.

PubMed

Camilloni, Carlo; Robustelli, Paul; De Simone, Alfonso; Cavalli, Andrea; Vendruscolo, Michele

2012-03-07

Following the recognition that NMR chemical shifts can be used for protein structure determination, rapid advances have recently been made in methods for extending this strategy for proteins and protein complexes of increasing size and complexity. A remaining major challenge is to develop approaches to exploit the information contained in the chemical shifts about conformational fluctuations in native states of proteins. In this work we show that it is possible to determine an ensemble of conformations representing the free energy surface of RNase A using chemical shifts as replica-averaged restraints in molecular dynamics simulations. Analysis of this surface indicates that chemical shifts can be used to characterize the conformational equilibrium between the two major substates of this protein. © 2012 American Chemical Society

Stress in crisis managers: evidence from self-report and psychophysiological assessments.

PubMed

Janka, A; Adler, C; Fischer, L; Perakakis, P; Guerra, P; Duschek, S

2015-12-01

Directing disaster operations represents a major professional challenge. Despite its importance to health and professional performance, research on stress in crisis management remains scarce. The present study aimed to investigate self-reported stress and psychophysiological stress responses in crisis managers. For this purpose, 30 crisis managers were compared with 30 managers from other disciplines, in terms of self-reported stress, health status and psychophysiological reactivity to crisis-related and non-specific visual and acoustic aversive stimuli and cognitive challenge. Crisis managers reported lower stress levels, a more positive strain-recuperation-balance, greater social resources, reduced physical symptoms, as well as more physical exercise and less alcohol consumption. They exhibited diminished electrodermal and heart rate responses to crisis-related and non-specific stressors. The results indicate reduced stress and physical complaints, diminished psychophysiological stress reactivity, and a healthier life-style in crisis managers. Improved stress resistance may limit vulnerability to stress-related performance decline and facilitate preparedness for major incidents.

Data warehousing in molecular biology.

PubMed

Schönbach, C; Kowalski-Saunders, P; Brusic, V

2000-05-01

In the business and healthcare sectors data warehousing has provided effective solutions for information usage and knowledge discovery from databases. However, data warehousing applications in the biological research and development (R&D) sector are lagging far behind. The fuzziness and complexity of biological data represent a major challenge in data warehousing for molecular biology. By combining experiences in other domains with our findings from building a model database, we have defined the requirements for data warehousing in molecular biology.

Catheter Ablation of Atrial Fibrillation in Patients with Hardware in the Heart - Septal Closure Devices, Mechanical Valves and More.

PubMed

Bartoletti, Stefano; Santangeli, Pasquale; DI Biase, Luigi; Natale, Andrea

2013-01-01

Patients with mechanical "hardware" in the heart, such as those with mechanical cardiac valves or atrial septal closure devices, represent a population at high risk of developing AF. Catheter ablation of AF in these subjects might represent a challenge, due to the perceived higher risk of complications associated with the presence of intracardiac mechanical devices. Accordingly, such patients were excluded or poorly represented in major trials proving the benefit of catheter ablation for the rhythm-control of AF. However, recent evidence supports the concept that catheter ablation procedures might be equally effective in these patients, without a significant increase in the risk of procedural complications. This review will summarize the current state-of-the-art on catheter ablation of AF in patients with mechanical "hardware" in the heart.

Challenges in Cost-Effectiveness Analysis Modelling of HPV Vaccines in Low- and Middle-Income Countries: A Systematic Review and Practice Recommendations.

PubMed

Ekwunife, Obinna I; O'Mahony, James F; Gerber Grote, Andreas; Mosch, Christoph; Paeck, Tatjana; Lhachimi, Stefan K

2017-01-01

Low- and middle-income countries (LMICs) face a number of challenges in implementing cervical cancer prevention programmes that do not apply in high-income countries. This review assessed how context-specific challenges of implementing cervical cancer prevention strategies in LMICs were accounted for in existing cost-effectiveness analysis (CEA) models of human papillomavirus (HPV) vaccination. The databases of MEDLINE, EMBASE, NHS Economic Evaluation Database, EconLit, Web of Science, and the Center for the Evaluation of Value and Risk in Health (CEA) Registry were searched for studies published from 2006 to 2015. A descriptive, narrative, and interpretative synthesis of data was undertaken. Of the 33 studies included in the review, the majority acknowledged cost per vaccinated girl (CVG) (26 studies) and vaccine coverage rate (21 studies) as particular challenges for LMICs, while nine studies identified screening coverage rate as a challenge. Most of the studies estimated CVG as a composite of different cost items. However, the basis for the items within this composite cost was unclear. The majority used an assumption rather than an observed rate to represent screening and vaccination coverage rates. CVG, vaccine coverage and screening coverage were shown by some studies through sensitivity analyses to reverse the conclusions regarding cost-effectiveness, thereby significantly affecting policy recommendations. While many studies recognized aspects of the particular challenges of HPV vaccination in LMICs, greater efforts need to be made in adapting models to account for these challenges. These include adapting costings of HPV vaccine delivery from other countries, learning from the outcomes of cervical cancer screening programmes in the same geographical region, and taking into account the country's previous experience with other vaccination programmes.

Economic benefits of supersonic overland operation

NASA Technical Reports Server (NTRS)

Metwally, Munir

1992-01-01

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

Collision Avoidance Short Course: Conjunction Assessment Risk Analysis - NASA Robotic CARA. Part I: ; Theory

NASA Technical Reports Server (NTRS)

Hejduk, M. D.; Frigm, Ryan C.

2015-01-01

Satellite conjunction assessment is perhaps the fastest growing area in space situational awareness and protection with military, civil and commercial satellite owner-operators embracing more and more sophisticated processes to avoid the avoidable - namely collisions between high value space assets and orbital debris. NASA and Centre National d'Etudes Spatiales (CNES) have collaborated to offer an introductory short course on all the major aspects of the conjunctions assessment problem. This half-day course will cover satellite conjunction dynamics and theory. Joint Space Operations Center (JsPOC) conjunction data products, major risk assessment parameters and plots, conjunction remediation decision support, and present and future challenges. This briefing represents the NASA portion of the course.

NATO AND TERRORISM Catastrophic Terrorism and First Responders: Threats and Mitigation

NASA Astrophysics Data System (ADS)

Steinhausler, Friedrich; Edwards, Frances

September 11, 2001 in the U.S., March 11, 2004 in Madrid -- just two examples of a series of major terror attacks against NATO member states on both sides of the Atlantic. We now know that international terrorism is capable of transboundary planning and military style execution of attacks, resulting in several thousand dead and wounded. In the future even larger terror attacks can no longer be ruled out, including the deployment of weapons of mass destruction. This new form of catastrophic terrorism poses a major challenge to the first responder community in their search and rescue operations, since these new threats represent an unprecedented risk for their health, possibly even questioning their own survival.

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

PubMed

Collins, Dave; MacNamara, Aine

2012-11-01

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

Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

PubMed

Moorthy, V S; Diggs, C; Ferro, S; Good, M F; Herrera, S; Hill, A V; Imoukhuede, E B; Kumar, S; Loucq, C; Marsh, K; Ockenhouse, C F; Richie, T L; Sauerwein, R W

2009-09-25

Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes.

The pain of chronic pancreatitis: a persistent clinical challenge

PubMed Central

2013-01-01

The pain of chronic pancreatitis represents a major challenge to those working in the field, including pain specialists, gastroenterologists and surgeons. This article describes the different aetiologies of chronic pancreatitis and lists the models for the pathogenesis of pain, including novel ideas such as the role of the immune system in the modulation of pain. The patient profile in chronic pancreatitis is discussed along with the social impact of the disease in relation to alcohol misuse. The range of treatment strategies including medical, endoscopic and surgical approaches are evaluated. Common analgesic regimes and their limitations are reviewed. The pain of chronic pancreatitis remains refractory to effective treatment in many cases and further study and understanding of the underlying pathophysiology are required. PMID:26516493

Under the sea: microbial life in volcanic oceanic crust.

PubMed

Edwards, Katrina J; Wheat, C Geoffrey; Sylvan, Jason B

2011-09-06

Exploration of the microbiology in igneous, 'hard rock' oceanic crust represents a major scientific frontier. The igneous crust harbours the largest aquifer system on Earth, most of which is hydrologically active, resulting in a substantial exchange of fluids, chemicals and microorganisms between oceanic basins and crustal reservoirs. Study of the deep-subsurface biosphere in the igneous crust is technically challenging. However, technologies have improved over the past decade, providing exciting new opportunities for the study of deep-seated marine life, including in situ and cross-disciplinary experimentation in microbiology, geochemistry and hydrogeology. In this Progress article, we describe the recent advances, available technology and remaining challenges in the study of the marine intraterrestrial microbial life that is harboured in igneous oceanic crust.

Musculoskeletal modelling in dogs: challenges and future perspectives.

PubMed

Dries, Billy; Jonkers, Ilse; Dingemanse, Walter; Vanwanseele, Benedicte; Vander Sloten, Jos; van Bree, Henri; Gielen, Ingrid

2016-05-18

Musculoskeletal models have proven to be a valuable tool in human orthopaedics research. Recently, veterinary research started taking an interest in the computer modelling approach to understand the forces acting upon the canine musculoskeletal system. While many of the methods employed in human musculoskeletal models can applied to canine musculoskeletal models, not all techniques are applicable. This review summarizes the important parameters necessary for modelling, as well as the techniques employed in human musculoskeletal models and the limitations in transferring techniques to canine modelling research. The major challenges in future canine modelling research are likely to centre around devising alternative techniques for obtaining maximal voluntary contractions, as well as finding scaling factors to adapt a generalized canine musculoskeletal model to represent specific breeds and subjects.

A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against Leishmania major

PubMed Central

Catharina, Larissa; Lima, Carlyle Ribeiro; Franca, Alexander; Guimarães, Ana Carolina Ramos; Alves-Ferreira, Marcelo; Tuffery, Pierre; Derreumaux, Philippe; Carels, Nicolas

2017-01-01

We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for L major compared with H sapiens, only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of L major and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with H sapiens. Among the 40 strictly specific enzymes, we identified sterol 24-C-methyltransferase, pyruvate phosphate dikinase, trypanothione synthetase, and RNA-editing ligase as 4 essential enzymes for L major that may serve as targets for drug development. PMID:28638238

A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against Leishmania major.

PubMed

Catharina, Larissa; Lima, Carlyle Ribeiro; Franca, Alexander; Guimarães, Ana Carolina Ramos; Alves-Ferreira, Marcelo; Tuffery, Pierre; Derreumaux, Philippe; Carels, Nicolas

2017-01-01

We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for L major compared with H sapiens , only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of L major and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with H sapiens . Among the 40 strictly specific enzymes, we identified sterol 24-C-methyltransferase, pyruvate phosphate dikinase, trypanothione synthetase, and RNA-editing ligase as 4 essential enzymes for L major that may serve as targets for drug development.

Full-mouth esthetic rehabilitation with acellular dermal matrix.

PubMed

Clozza, Emanuele; Suzuki, Takanori; Engebretson, Steven P

2014-01-01

Treatment of multiple recession defects with the adjunct use of a connective tissue graft (CTG) represents a challenge when diagnosed in several teeth of the mouth. The amount of CTG harvested from the palate may not be adequate to address this condition. In such scenarios, alternative sources such as acellular dermal matrix (ADM) are preferred due to the unlimited availability. A case report is presented, dealing with the treatment of multiple gingival recessions affecting the majority of dentition using ADM, with a 6-month follow-up.

Human Plasma Enhances the Expression of Staphylococcal Microbial Surface Components Recognizing Adhesive Matrix Molecules Promoting Biofilm Formation and Increases Antimicrobial Tolerance In Vitro

DTIC Science & Technology

2014-07-17

infection and invasion in Staphylococcus aureus experimental endocarditis . J Exp Med 2005, 201:1627 1635. 23. Atshan SS, Shamsudin MN, Karunanidhi A, van... infections . The ability of S. aureus to colonize and establish biofilms, a surface- attached microbial community surrounded by a self- produced polymeric...human infections [2-4], and represent a major challenge to modern medicine given their recalcitrance to antimicrobials and host mechanisms of clearance

Space shuttle program solid rocket booster decelerator subsystem

NASA Technical Reports Server (NTRS)

Barnard, J. W.

1985-01-01

The recovery of the Solid Rocket Boosters presented a major challenge. The SRB represents the largest payload ever recovered and presents the added complication that it is continually emitting hot gases and burning particles of insulation and other debris. Some items, such as portions of the nozzle, are large enough to burn through the nylon parachute material. The SRB Decelerator Subsystem program was highly successful in that no SRB has been lost as a result of inadequate performance of the DSS.

Psychiatry and the 'Gay Holocaust' - the lessons of Jill Soloway's Transparent.

PubMed

Robertson, Michael D; Light, Edwina; Walter, Garry; Lipworth, Wendy

2016-12-01

We aim to consider issues relevant to psychiatry raised by the television series, Transparent. Psychiatry's disturbing history regarding the lesbian, gay, bisexual, transgender and intersex (LGBTI) community shares many aspects with the group's persecution by the National Socialist regime in Germany. The medicalised 'otherness' conferred on LGBTI patients, latent homophobia and transphobia, and lack of culturally sensitive clinical services for these people represent a major ethical challenge for modern Australasian psychiatry. © The Royal Australian and New Zealand College of Psychiatrists 2016.

Social Ontology Documentation for Knowledge Externalization

NASA Astrophysics Data System (ADS)

Aranda-Corral, Gonzalo A.; Borrego-Díaz, Joaquín; Jiménez-Mavillard, Antonio

Knowledge externalization and organization is a major challenge that companies must face. Also, they have to ask whether is possible to enhance its management. Mechanical processing of information represents a chance to carry out these tasks, as well as to turn intangible knowledge assets into real assets. Machine-readable knowledge provides a basis to enhance knowledge management. A promising approach is the empowering of Knowledge Externalization by the community (users, employees). In this paper, a social semantic tool (called OntoxicWiki) for enhancing the quality of knowledge is presented.

Single-Cell RNA-Seq Reveals Transcriptional Heterogeneity in Latent and Reactivated HIV-Infected Cells.

PubMed

Golumbeanu, Monica; Cristinelli, Sara; Rato, Sylvie; Munoz, Miguel; Cavassini, Matthias; Beerenwinkel, Niko; Ciuffi, Angela

2018-04-24

Despite effective treatment, HIV can persist in latent reservoirs, which represent a major obstacle toward HIV eradication. Targeting and reactivating latent cells is challenging due to the heterogeneous nature of HIV-infected cells. Here, we used a primary model of HIV latency and single-cell RNA sequencing to characterize transcriptional heterogeneity during HIV latency and reactivation. Our analysis identified transcriptional programs leading to successful reactivation of HIV expression. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Knowledge representation in metabolic pathway databases.

PubMed

Stobbe, Miranda D; Jansen, Gerbert A; Moerland, Perry D; van Kampen, Antoine H C

2014-05-01

The accurate representation of all aspects of a metabolic network in a structured format, such that it can be used for a wide variety of computational analyses, is a challenge faced by a growing number of researchers. Analysis of five major metabolic pathway databases reveals that each database has made widely different choices to address this challenge, including how to deal with knowledge that is uncertain or missing. In concise overviews, we show how concepts such as compartments, enzymatic complexes and the direction of reactions are represented in each database. Importantly, also concepts which a database does not represent are described. Which aspects of the metabolic network need to be available in a structured format and to what detail differs per application. For example, for in silico phenotype prediction, a detailed representation of gene-protein-reaction relations and the compartmentalization of the network is essential. Our analysis also shows that current databases are still limited in capturing all details of the biology of the metabolic network, further illustrated with a detailed analysis of three metabolic processes. Finally, we conclude that the conceptual differences between the databases, which make knowledge exchange and integration a challenge, have not been resolved, so far, by the exchange formats in which knowledge representation is standardized.

Unraveling the Tissue-Specific Gene Signatures of Gilthead Sea Bream (Sparus aurata L.) after Hyper- and Hypo-Osmotic Challenges

PubMed Central

Martos-Sitcha, Juan Antonio; Mancera, Juan Miguel; Calduch-Giner, Josep Alvar; Yúfera, Manuel; Martínez-Rodríguez, Gonzalo; Pérez-Sánchez, Jaume

2016-01-01

A custom microarray was used for the transcriptomic profiling of liver, gills and hypothalamus in response to hypo- (38‰ → 5‰) or hyper- (38‰ → 55‰) osmotic challenges (7 days after salinity transfer) in gilthead sea bream (Sparus aurata) juveniles. The total number of differentially expressed genes was 777. Among them, 341 and 310 were differentially expressed in liver after hypo- and hyper-osmotic challenges, respectively. The magnitude of changes was lower in gills and hypothalamus with around 131 and 160 responsive genes in at least one osmotic stress condition, respectively. Regardless of tissue, a number of genes were equally regulated in either hypo- and hyper-osmotic challenges: 127 out of 524 in liver, 11 out of 131 in gills and 19 out of 160 in hypothalamus. In liver and gills, functional analysis of differentially expressed genes recognized two major clusters of overlapping canonical pathways that were mostly related to “Energy Metabolism” and “Oxidative Stress”. The later cluster was represented in all the analyzed tissues, including the hypothalamus, where differentially expressed genes related to “Cell and tissue architecture” were also over-represented. Overall the response for “Energy Metabolism” was the up-regulation, whereas for oxidative stress-related genes the type of response was highly dependent of tissue. These results support common and different osmoregulatory responses in the three analyzed tissues, helping to load new allostatic conditions or even to return to basal levels after hypo- or hyper-osmotic challenges according to the different physiological role of each tissue. PMID:26828928

Bacterial signaling ecology and potential applications during aquatic biofilm construction.

PubMed

Vega, Leticia M; Alvarez, Pedro J; McLean, Robert J C

2014-07-01

In their natural environment, bacteria and other microorganisms typically grow as surface-adherent biofilm communities. Cell signal processes, including quorum signaling, are now recognized as being intimately involved in the development and function of biofilms. In contrast to their planktonic (unattached) counterparts, bacteria within biofilms are notoriously resistant to many traditional antimicrobial agents and so represent a major challenge in industry and medicine. Although biofilms impact many human activities, they actually represent an ancient mode of bacterial growth as shown in the fossil record. Consequently, many aquatic organisms have evolved strategies involving signal manipulation to control or co-exist with biofilms. Here, we review the chemical ecology of biofilms and propose mechanisms whereby signal manipulation can be used to promote or control biofilms.

The role of community and population ecology in applying mycorrhizal fungi for improved food security

PubMed Central

Rodriguez, Alia; Sanders, Ian R

2015-01-01

The global human population is expected to reach ∼9 billion by 2050. Feeding this many people represents a major challenge requiring global crop yield increases of up to 100%. Microbial symbionts of plants such as arbuscular mycorrhizal fungi (AMF) represent a huge, but unrealized resource for improving yields of globally important crops, especially in the tropics. We argue that the application of AMF in agriculture is too simplistic and ignores basic ecological principals. To achieve this challenge, a community and population ecology approach can contribute greatly. First, ecologists could significantly improve our understanding of the determinants of the survival of introduced AMF, the role of adaptability and intraspecific diversity of AMF and whether inoculation has a direct or indirect effect on plant production. Second, we call for extensive metagenomics as well as population genomics studies that are crucial to assess the environmental impact that introduction of non-local AMF may have on native AMF communities and populations. Finally, we plead for an ecologically sound use of AMF in efforts to increase food security at a global scale in a sustainable manner. PMID:25350159

The role of community and population ecology in applying mycorrhizal fungi for improved food security.

PubMed

Rodriguez, Alia; Sanders, Ian R

2015-05-01

The global human population is expected to reach ∼9 billion by 2050. Feeding this many people represents a major challenge requiring global crop yield increases of up to 100%. Microbial symbionts of plants such as arbuscular mycorrhizal fungi (AMF) represent a huge, but unrealized resource for improving yields of globally important crops, especially in the tropics. We argue that the application of AMF in agriculture is too simplistic and ignores basic ecological principals. To achieve this challenge, a community and population ecology approach can contribute greatly. First, ecologists could significantly improve our understanding of the determinants of the survival of introduced AMF, the role of adaptability and intraspecific diversity of AMF and whether inoculation has a direct or indirect effect on plant production. Second, we call for extensive metagenomics as well as population genomics studies that are crucial to assess the environmental impact that introduction of non-local AMF may have on native AMF communities and populations. Finally, we plead for an ecologically sound use of AMF in efforts to increase food security at a global scale in a sustainable manner.

Using Grand Challenges to Teach Science: A Biology-Geology Collaboration

NASA Astrophysics Data System (ADS)

Lyford, M.; Myers, J. D.

2012-12-01

Three science courses at the University of Wyoming explore the inextricable connections between science and society by centering on grand challenges. Two of these courses are introductory integrated science courses for non-majors while the third is an upper level course for majors and non-majors. Through collaboration, the authors have developed these courses to explore the grand challenges of energy, water and climate. Each course focuses on the fundamental STEM principles required for a citizen to understand each grand challenge. However, the courses also emphasize the non-STEM perspectives (e.g., economics, politics, human well-being, externalities) that underlie each grand challenge and argue that creating equitable, sustainable and just solutions to the grand challenges hinges on an understanding of STEM and non-STEM perspectives. Moreover, the authors also consider the multitude of personal perspectives individuals bring to the classroom (e.g., values, beliefs, empathy misconceptions) that influence any stakeholder's ability to engage in fruitful discussions about grand challenge solutions. Discovering Science (LIFE 1002) focuses on the grand challenges of energy and climate. Students attend three one-hour lectures, one two-hour lab and a one-hour discussion each week. Lectures emphasize the STEM and non-STEM principles underlying each grand challenge. Laboratory activities are designed to be interdisciplinary and engage students in inquiry-driven activities to reinforce concepts from lecture and to model how science is conducted. Labs also expose students to the difficulties often associated with scientific studies, the limits of science, and the inherent uncertainties associated with scientific findings. Discussion sessions provide an opportunity for students to explore the complexity of the grand challenges from STEM and non-STEM perspectives, and expose the multitude of personal perspectives an individual might harbor related to each grand challenge. Global Sustainability: Managing Earth's Resources (GEOL 1600) focuses on the energy-water climate nexus with a similar emphasis on STEM and non-STEM perspectives as LIFE 1002. Each week, there are three one hour lectures and a two hour lab. To set the stage for global and systems thinking, the concept of the Anthropocene and planetary boundaries are introduced early in the semester. Lectures focus on a variety of energy-water-climate topics and provide the content background for the labs. Labs are mini-case studies that address a variety of issues set in different global contexts, e.g. groundwater in Bangladesh, coal in China and petroleum in Saudi Arabia. Often the labs cover two weeks with one part covering science and the other economics. Unlike the other two courses, Energy: A Geological Perspective (GEOL 3650), is enrolled with half geology majors and half non-majors, representing almost every college on campus. Its organizational structure is similar to 1600. Labs focus on case studies, each lasting from 3 to 5 weeks, with each week addressing a different aspect of the same issue and social context, e.g. geology, economics, engineering, regulatory and political/social. Students, working in groups, present oral and written reports. Topics range from nuclear power and weapons in Iran to atmospheric emissions and global climate treaties.

Boosting innate immunity to sustainably control diseases in crops.

PubMed

Nicaise, Valerie

2017-10-01

Viruses cause epidemics in all major crops, threatening global food security. The development of efficient and durable resistance able to withstand viral attacks represents a major challenge for agronomy, and relies greatly on the understanding of the molecular dialogue between viral pathogens and their hosts. Research over the last decades provided substantial advances in the field of plant-virus interactions. Remarkably, the advent of studies of plant innate immunity has recently offered new strategies exploitable in the field. This review summarizes the recent breakthroughs that define the mechanisms underlying antiviral innate immunity in plants, and emphasizes the importance of integrating that knowledge into crop improvement actions, particularly by exploiting the insights related to immune receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

Sidestepping questions of legitimacy: how community representatives manoeuvre to effect change in a health service.

PubMed

Nathan, Sally; Stephenson, Niamh; Braithwaite, Jeffrey

2014-01-01

Empirical studies of community participation in health services commonly tie effectiveness to the perceived legitimacy of community representatives among health staff. This article examines the underlying assumption that legitimacy is the major pathway to influence for community representatives. It takes a different vantage point from previous research in its examination of data (primarily through 34 in-depth interviews, observation and recording of 26 meetings and other interactions documented in field notes) from a 3-year study of community representatives' action in a large health region in Australia. The analysis primarily deploys Michel de Certeau's ideas of Strategy and Tactic to understand the action and effects of the generally 'weaker players' in the spaces and places dominated by powerful institutions. Through this lens, we can see the points where community representatives are active participants following their own agenda, tactically capitalising on cracks in the armour of the health service to seize opportunities that present themselves in time to effect change. Being able to see community representatives as active producers of change, not simply passengers following the path of the health service, challenges how we view the success of community participation in health.

Opportunities and challenges for HIV care in overlapping HIV and TB epidemics.

PubMed

Havlir, Diane V; Getahun, Haileyesus; Sanne, Ian; Nunn, Paul

2008-07-23

Tuberculosis (TB) and the emerging multidrug-resistant TB epidemic represent major challenges to human immunodeficiency virus (HIV) care and treatment programs in resource-limited settings. Tuberculosis is a major cause of mortality among patients with HIV and poses a risk throughout the course of HIV disease, even after successful initiation of antiretroviral therapy (ART). Progress in the implementation of activities directed at reducing TB burden in the HIV population lags far behind global targets. HIV programs designed for longitudinal care are ideally suited to implement TB control measures and have no option but to address TB vigorously to save patient lives, to safeguard the massive investment in HIV treatment, and to curb the global TB burden. We propose a framework of strategic actions for HIV care programs to optimally integrate TB into their services. The core activities of this framework include intensified TB case finding, treatment of TB, isoniazid preventive treatment, infection control, administration of ART, TB recording and reporting, and joint efforts of HIV and TB programs at the national and local levels.

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

PubMed

Rosenbaum, Sara

2015-02-01

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

Plant biomass degrading ability of the coprophilic ascomycete fungus Podospora anserina.

PubMed

Couturier, Marie; Tangthirasunun, Narumon; Ning, Xie; Brun, Sylvain; Gautier, Valérie; Bennati-Granier, Chloé; Silar, Philippe; Berrin, Jean-Guy

2016-01-01

The degradation of plant biomass is a major challenge towards the production of bio-based compounds and materials. As key lignocellulolytic enzyme producers, filamentous fungi represent a promising reservoir to tackle this challenge. Among them, the coprophilous ascomycete Podospora anserina has been used as a model organism to study various biological mechanisms because its genetics are well understood and controlled. In 2008, the sequencing of its genome revealed a great diversity of enzymes targeting plant carbohydrates and lignin. Since then, a large array of lignocellulose-acting enzymes has been characterized and genetic analyses have enabled the understanding of P. anserina metabolism and development on plant biomass. Overall, these research efforts shed light on P. anserina strategy to unlock recalcitrant lignocellulose deconstruction. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

Gellert, G A

1996-01-01

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

[Genetic mutation databases: stakes and perspectives for orphan genetic diseases].

PubMed

Humbertclaude, V; Tuffery-Giraud, S; Bareil, C; Thèze, C; Paulet, D; Desmet, F-O; Hamroun, D; Baux, D; Girardet, A; Collod-Béroud, G; Khau Van Kien, P; Roux, A-F; des Georges, M; Béroud, C; Claustres, M

2010-10-01

New technologies, which constantly become available for mutation detection and gene analysis, have contributed to an exponential rate of discovery of disease genes and variation in the human genome. The task of collecting and documenting this enormous amount of data in genetic databases represents a major challenge for the future of biological and medical science. The Locus Specific Databases (LSDBs) are so far the most efficient mutation databases. This review presents the main types of databases available for the analysis of mutations responsible for genetic disorders, as well as open perspectives for new therapeutic research or challenges for future medicine. Accurate and exhaustive collection of variations in human genomes will be crucial for research and personalized delivery of healthcare. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

Challenges in Drug Discovery for Neurofibromatosis Type 1-Associated Low-Grade Glioma

PubMed Central

Ricker, Cora A.; Pan, Yuan; Gutmann, David H.; Keller, Charles

2016-01-01

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that results from germline mutations of the NF1 gene, creating a predisposition to low-grade gliomas (LGGs; pilocytic astrocytoma) in young children. Insufficient data and resources represent major challenges to identifying the best possible drug therapies for children with this tumor. Herein, we summarize the currently available cell lines, genetically engineered mouse models, and therapeutic targets for these LGGs. Conspicuously absent are human tumor-derived cell lines or patient-derived xenograft models for NF1-LGG. New collaborative initiatives between patients and their families, research groups, and pharmaceutical companies are needed to create transformative resources and broaden the knowledge base relevant to identifying cooperating genetic drivers and possible drug therapeutics for this common pediatric brain tumor. PMID:28066715

The Y.E.S. Network: An IYPE legacy for engaging future generations of early-career geoscientists

NASA Astrophysics Data System (ADS)

Gonzales, L. M.; Govoni, D.; Micucci, L.; Gaines, S. M.; Venus, J.; Meng, W.

2009-12-01

The Y.E.S. Network, an association of early-career geoscientists who represent professional societies, geoscience companies, and geoscience departments from across the world, was formed as a direct result of the International Year of Planet Earth (IYPE). Currently the Y.E.S. Network has representatives in thirty-five countries from six continents. The goal of the network is to engage early-career representatives from geological associations and institutions, policy-makers, and delegates from administrative bodies to establish a worldwide network of future leaders, policy-makers and geoscientists who will work collaboratively to address the scientific challenges future generations will face. To this end, the Y.E.S. Network, in collaboration with IYPE and with the patronage of UNESCO, organized the first international Y.E.S. Congress which was hosted by the China University of Geosciences in Beijing. The conference focused on scientific and career challenges faced by early-career geoscientists, with a particular emphasis on how the Y.E.S. Network can work collaborative and internationally towards solving these challenges and furthering the IYPE motto of “Earth Sciences for Society”. The conference focused on the ten major themes of the IYPE (e.g. health, climate, groundwater, ocean, soils, deep earth, megacities, hazards, resources, and life) at its poster and oral sessions. Roundtable symposia engaged senior and early-career geoscientists via presentations, panel discussions, and working group sessions where strategies related to scientific challenges (i.e. climate change in the polar regions, natural hazards, natural resource sustainability) and academic and career pathway challenges (i.e. academic-industry linkages, gender parity in the geosciences, geoscience education sustainability, and international licensure issues) were developed. These strategies were then tasked to the Y.E.S. Network for further development and implementation. Future Y.E.S. Network activities include the development of an interactive Y.E.S. Network website that will enable Y.E.S. country representative to post relevant events and activities, and will facilitate continued collaboration between Y.E.S. Network members on the strategies developed at the Y.E.S. Congress roundtable symposia. The next international Y.E.S. Congress will be held in conjunction with the 34th IGC in Brisbane, Australia in August 2012.

Phytochemicals as Prototypes for Pharmaceutical Leads Towards Drug Development Against Diabetic Cardiomyopathy.

PubMed

Ojha, Shreesh; Kurdi, Amani; Sadek, Bassem; Kaleem, M; Cai, Lu; Kamal, M A; Rajesh, Mohanraj

2016-01-01

Globally diabetes mellitus (DM) is swiftly reaching epidemic proportions and impose major health care and socio-economic challenges that are associated with its complications. DM is considered as the major risk factor for the development of debilitating micro & macro vascular complications. Clinical studies have revealed that development of diabetic cardiomyopathy (DCM) in subjects with diabetes can occur both- dependent and independent of pre-existing increased risk factors such as poor glycemic control, hyperlipidemia, and or hypertension. Therefore, DCM represents as a major challenge for the clinical community for the prompt diagnosis and devising the treatment paradigm to combat the diabetes induced cardiac dysfunction. In Chinese traditional medical practice, heart ailments have been coped with herbal extracts. Phytochemicals bioavailability and pharmacokinetic properties are to yet be established completely in human subjects. However, tremendous progress has been made to isolate, purify the phytochemicals and characterize their effects on mitigating the development of DCM in pre-clinical models. Currently there are no approved drugs available for the treatment of DCM. In this review, we have discussed the progress made in understanding the mechanisms for the phytochemicals cardio-protective actions in the diabetic milieu and their caveats and provide future perspectives for proposing these agents to serve as prototypes in the development of drugs for the management of DCM.

Major Management Challenges and Program Risks. Department of Education

DTIC Science & Technology

2001-01-01

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

Book Analysis: Challenger: A Major Malfunction.

DTIC Science & Technology

1988-04-01

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

Identification and Characterization of Psychrotolerant Sporeformers Associated with Fluid Milk Production and Processing

PubMed Central

Ivy, Reid A.; Ranieri, Matthew L.; Martin, Nicole H.; den Bakker, Henk C.; Xavier, Bruno M.; Wiedmann, Martin

2012-01-01

Psychrotolerant spore-forming bacteria represent a major challenge to the goal of extending the shelf life of pasteurized dairy products. The objective of this study was to identify prominent phylogenetic groups of dairy-associated aerobic sporeformers and to characterize representative isolates for phenotypes relevant to growth in milk. Analysis of sequence data for a 632-nucleotide fragment of rpoB showed that 1,288 dairy-associated isolates (obtained from raw and pasteurized milk and from dairy farm environments) clustered into two major divisions representing (i) the genus Paenibacillus (737 isolates, including the species Paenibacillus odorifer, Paenibacillus graminis, and Paenibacillus amylolyticus sensu lato) and (ii) Bacillus (n = 467) (e.g., Bacillus licheniformis sensu lato, Bacillus pumilus, Bacillus weihenstephanensis) and genera formerly classified as Bacillus (n = 84) (e.g., Viridibacillus spp.). When isolates representing the most common rpoB allelic types (ATs) were tested for growth in skim milk broth at 6°C, 6/9 Paenibacillus isolates, but only 2/8 isolates representing Bacillus subtypes, grew >5 log CFU/ml over 21 days. In addition, 38/40 Paenibacillus isolates but only 3/47 Bacillus isolates tested were positive for β-galactosidase activity (including some isolates representing Bacillus licheniformis sensu lato, a common dairy-associated clade). Our study confirms that Paenibacillus spp. are the predominant psychrotolerant sporeformers in fluid milk and provides 16S rRNA gene and rpoB subtype data and phenotypic characteristics facilitating the identification of aerobic spore-forming spoilage organisms of concern. These data will be critical for the development of detection methods and control strategies that will reduce the introduction of psychrotolerant sporeformers and extend the shelf life of dairy products. PMID:22247129

Late post-treatment radiographic changes 3 years following chemoradiation for glioma: the importance of histopathology.

PubMed

Galante, Joao R; Rodriguez, Fausto; Grossman, Stuart A; Strowd, Roy E

2017-07-18

Treatment-related changes can mimic brain tumor progression both clinically and radiographically. Distinguishing these two entities represents a major challenge in neuro-oncology. No single imaging modality is capable of reliably achieving such distinction. While histopathology remains the gold standard, definitive pathological criteria are also lacking which can further complicate such cases. We report a patient with high-grade glioma who, after initially presenting with histopathologically confirmed pseudoprogression 10 months following treatment, re-presented 3 years following concurrent chemoradiation with clinical and radiographic changes that were most consistent with progressive disease but for which histopathology revealed treatment effects without active glioma. This case highlights the potential late onset of treatment-related changes and underscores the importance of histopathologic assessment even years following initial therapy.

Malaria films: Motion pictures as a public health tool.

PubMed

Fedunkiw, Marianne

2003-07-01

I offer a historical examination of a group of malaria motion pictures, a subset of a larger genre of public health films. The majority of these more than 100 films were produced or coproduced by American and British agencies or production companies since 1940. The material is divided into 5 chronological periods, which include World War II, the postcolonial or DDT era (1946-1961), and the past 2 decades. The films themselves, I argue, represent a unique record of preventive measures, clinical techniques, and sociocultural biases, all within the context of a history of one of the greatest continuing challenges in public health. The malaria films, as a group, represent a large body of work that has not yet been brought together or analyzed as historical sources.

Malaria Films: Motion Pictures as a Public Health Tool

PubMed Central

Fedunkiw, Marianne

2003-01-01

I offer a historical examination of a group of malaria motion pictures, a subset of a larger genre of public health films. The majority of these more than 100 films were produced or coproduced by American and British agencies or production companies since 1940. The material is divided into 5 chronological periods, which include World War II, the postcolonial or DDT era (1946–1961), and the past 2 decades. The films themselves, I argue, represent a unique record of preventive measures, clinical techniques, and sociocultural biases, all within the context of a history of one of the greatest continuing challenges in public health. The malaria films, as a group, represent a large body of work that has not yet been brought together or analyzed as historical sources. PMID:12835178

The Role of Femoroacetabular Impingement in Core Muscle Injury/Athletic Pubalgia: Diagnosis and Management.

PubMed

Strosberg, David S; Ellis, Thomas J; Renton, David B

2016-01-01

Chronic groin pain in athletes represents a major diagnostic and therapeutic challenge in sports medicine. Two recognized causes of inguinal pain in the young adult athlete are core muscle injury/athletic pubalgia (CMI/AP) and femoroacetabular impingement (FAI). CMI/AP and FAI were previously considered to be two distinct entities; however, recent studies have suggested both entities to frequently coincide in the athlete with groin pain. This article briefly discusses the role of FAI in CMI/AP and the diagnosis and management of this complex disease.

The Role of Femoroacetabular Impingement in Core Muscle Injury/Athletic Pubalgia: Diagnosis and Management

PubMed Central

Strosberg, David S.; Ellis, Thomas J.; Renton, David B.

2016-01-01

Chronic groin pain in athletes represents a major diagnostic and therapeutic challenge in sports medicine. Two recognized causes of inguinal pain in the young adult athlete are core muscle injury/athletic pubalgia (CMI/AP) and femoroacetabular impingement (FAI). CMI/AP and FAI were previously considered to be two distinct entities; however, recent studies have suggested both entities to frequently coincide in the athlete with groin pain. This article briefly discusses the role of FAI in CMI/AP and the diagnosis and management of this complex disease. PMID:26904546

Bone-Immune Cell Crosstalk: Bone Diseases

PubMed Central

Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta

2015-01-01

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma. PMID:26000310

Bone-immune cell crosstalk: bone diseases.

PubMed

Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta; Brunetti, Giacomina

2015-01-01

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma.

Lignin carbon fiber: The path for quality

DOE PAGES

Yuan, Joshua S.; Li, Qiang; Ragauskas, Arthur J.

2017-03-01

Lignin represents an abundant biopolymer and a major waste from lignocellulosic processing plants, yet the utilization of lignin for fungible products remains one of the most challenging technical barriers for pulp mills and the modern biorefinery industry. In recent decades, lignin has been sought after as a precursor polymer for carbon fiber due to the high carbon content (up to 60%). Furthermore lignin carbon fiber is expected to be compatible with the market size of the pulp and paper industry and may have transformative impact on petroleum-based carbon fiber.

Bottomland Hardwood Forests along the Upper Mississippi River

USGS Publications Warehouse

Yin, Y.; Nelson, J.C.; Lubinski, S.J.

1997-01-01

Bottomland hardwood forests along the United States' Upper Mississippi River have been drastically reduced in acreage and repeatedly logged during the nineteenth and twentieth centuries. Conversion to agricultural land, timber harvesting, and river modifications for flood prevention and for navigation were the primary factors that caused the changes. Navigation structures and flood-prevention levees have altered the fluvial geomorphic dynamics of the river and floodplain system. Restoration and maintenance of the diversity, productivity, and natural regeneration dynamics of the bottomland hardwood forests under the modified river environment represent a major management challenge.

Meta-control of combustion performance with a data mining approach

NASA Astrophysics Data System (ADS)

Song, Zhe

Large scale combustion process is complex and proposes challenges of optimizing its performance. Traditional approaches based on thermal dynamics have limitations on finding optimal operational regions due to time-shift nature of the process. Recent advances in information technology enable people collect large volumes of process data easily and continuously. The collected process data contains rich information about the process and, to some extent, represents a digital copy of the process over time. Although large volumes of data exist in industrial combustion processes, they are not fully utilized to the level where the process can be optimized. Data mining is an emerging science which finds patterns or models from large data sets. It has found many successful applications in business marketing, medical and manufacturing domains The focus of this dissertation is on applying data mining to industrial combustion processes, and ultimately optimizing the combustion performance. However the philosophy, methods and frameworks discussed in this research can also be applied to other industrial processes. Optimizing an industrial combustion process has two major challenges. One is the underlying process model changes over time and obtaining an accurate process model is nontrivial. The other is that a process model with high fidelity is usually highly nonlinear, solving the optimization problem needs efficient heuristics. This dissertation is set to solve these two major challenges. The major contribution of this 4-year research is the data-driven solution to optimize the combustion process, where process model or knowledge is identified based on the process data, then optimization is executed by evolutionary algorithms to search for optimal operating regions.

Weather forecasting based on hybrid neural model

NASA Astrophysics Data System (ADS)

Saba, Tanzila; Rehman, Amjad; AlGhamdi, Jarallah S.

2017-11-01

Making deductions and expectations about climate has been a challenge all through mankind's history. Challenges with exact meteorological directions assist to foresee and handle problems well in time. Different strategies have been investigated using various machine learning techniques in reported forecasting systems. Current research investigates climate as a major challenge for machine information mining and deduction. Accordingly, this paper presents a hybrid neural model (MLP and RBF) to enhance the accuracy of weather forecasting. Proposed hybrid model ensure precise forecasting due to the specialty of climate anticipating frameworks. The study concentrates on the data representing Saudi Arabia weather forecasting. The main input features employed to train individual and hybrid neural networks that include average dew point, minimum temperature, maximum temperature, mean temperature, average relative moistness, precipitation, normal wind speed, high wind speed and average cloudiness. The output layer composed of two neurons to represent rainy and dry weathers. Moreover, trial and error approach is adopted to select an appropriate number of inputs to the hybrid neural network. Correlation coefficient, RMSE and scatter index are the standard yard sticks adopted for forecast accuracy measurement. On individual standing MLP forecasting results are better than RBF, however, the proposed simplified hybrid neural model comes out with better forecasting accuracy as compared to both individual networks. Additionally, results are better than reported in the state of art, using a simple neural structure that reduces training time and complexity.

Functional modules, mutational load and human genetic disease.

PubMed

Zaghloul, Norann A; Katsanis, Nicholas

2010-04-01

The ability to generate a massive amount of sequencing and genotyping data is transforming the study of human genetic disorders. Driven by such innovation, it is likely that whole exome and whole-genome resequencing will replace regionally focused approaches for gene discovery and clinical testing in the next few years. However, this opportunity brings a significant interpretative challenge to assigning function and phenotypic variance to common and rare alleles. Understanding the effect of individual mutations in the context of the remaining genomic variation represents a major challenge to our interpretation of disease. Here, we discuss the challenges of assigning mutation functionality and, drawing from the examples of ciliopathies as well as cohesinopathies and channelopathies, discuss possibilities for the functional modularization of the human genome. Functional modularization in addition to the development of physiologically relevant assays to test allele functionality will accelerate our understanding of disease architecture and enable the use of genome-wide sequence data for disease diagnosis and phenotypic prediction in individuals. Copyright 2010 Elsevier Ltd. All rights reserved.

Functional modules, mutational load and human genetic disease

PubMed Central

Zaghloul, Norann A.; Katsanis, Nicholas

2013-01-01

The ability to generate a massive amount of sequencing and genotyping data is transforming the study of human genetic disorders. Driven by such innovation, it is likely that whole exome and whole-genome resequencing will replace regionally focused approaches for gene discovery and clinical testing in the next few years. However, this opportunity brings a significant interpretative challenge to assigning function and phenotypic variance to common and rare alleles. Understanding the effect of individual mutations in the context of the remaining genomic variation represents a major challenge to our interpretation of disease. Here, we discuss the challenges of assigning mutation functionality and, drawing from the examples of ciliopathies as well as cohesinopathies and channelopathies, discuss possibilities for the functional modularization of the human genome. Functional modularization in addition to the development of physiologically-relevant assays to test allele functionality will accelerate our understanding of disease architecture and enable the use of genome-wide sequence data for disease diagnosis and phenotypic prediction in individuals. PMID:20226561

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

PubMed

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

2014-01-01

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

Strengthening malaria prevention and control: integrating West African militaries' malaria control efforts. The inaugural meeting of the West African Malaria Task Force, April 24-26, 2013, Accra, Ghana.

PubMed

McCollum, Jeffrey T; Hanna, Refaat; Halbach, Alaina C; Cummings, James F

2015-01-01

From April 24 to 26, 2013, the Armed Forces Health Surveillance Center and the U.S. Africa Command cosponsored the inaugural meeting of the West Africa Malaria Task Force in Accra, Ghana. The meeting's purpose was to identify common challenges, explore regional and transcontinental collaborations, and to share knowledge about best practices in the fight against malaria in West Africa. Military representatives from Benin, Burkina Faso, Ghana, Liberia, Niger, Nigeria, Senegal, and Togo participated in the Task Force; various U.S. Government agencies were also represented, including the Department of Defense, the Centers for Disease Control and Prevention, and the Agency for International Development. African nation participants presented brief overviews of their military's malaria prevention and control measures, surveillance programs, diagnostic capabilities, and treatment regimens emphasizing gaps within existing programs. Representatives from U.S. agencies discussed activities and capabilities relevant for the region, challenges and lessons learned regarding malaria, and highlighted opportunities for enhanced partnerships to counter malaria in West Africa. This article summarizes the major conclusions of the Task Force meeting, identifies relevant focus areas for future Task Force activities, and outlines opportunities for further inclusion of West African militaries to improve regional malaria surveillance and control efforts. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Thinking Beyond the Silos: Emerging Priorities in Workforce Development for State and Local Government Public Health Agencies

PubMed Central

Kaufman, Nancy J.; Castrucci, Brian C.; Pearsol, Jim; Leider, Jonathon P.; Sellers, Katie; Kaufman, Ira R.; Fehrenbach, Lacy M.; Liss-Levinson, Rivka; Lewis, Melissa; Jarris, Paul E.; Sprague, James B.

2014-01-01

Context: Discipline-specific workforce development initiatives have been a focus in recent years. This is due, in part, to competency-based training standards and funding sources that reinforce programmatic silos within state and local health departments. Objective: National leadership groups representing the specific disciplines within public health were asked to look beyond their discipline-specific priorities and collectively assess the priorities, needs, and characteristics of the governmental public health workforce. Design: The challenges and opportunities facing the public health workforce and crosscutting priority training needs of the public health workforce as a whole were evaluated. Key informant interviews were conducted with 31 representatives from public health member organizations and federal agencies. Interviews were coded and analyzed for major themes. Next, 10 content briefs were created on the basis of priority areas within workforce development. Finally, an in-person priority setting meeting was held to identify top workforce development needs and priorities across all disciplines within public health. Participants: Representatives from 31 of 37 invited public health organizations participated, including representatives from discipline-specific member organizations, from national organizations and from federal agencies. Results: Systems thinking, communicating persuasively, change management, information and analytics, problem solving, and working with diverse populations were the major crosscutting areas prioritized. Conclusions: Decades of categorical funding created a highly specialized and knowledgeable workforce that lacks many of the foundational skills now most in demand. The balance between core and specialty training should be reconsidered. PMID:24667228

Thinking beyond the silos: emerging priorities in workforce development for state and local government public health agencies.

PubMed

Kaufman, Nancy J; Castrucci, Brian C; Pearsol, Jim; Leider, Jonathon P; Sellers, Katie; Kaufman, Ira R; Fehrenbach, Lacy M; Liss-Levinson, Rivka; Lewis, Melissa; Jarris, Paul E; Sprague, James B

2014-01-01

Discipline-specific workforce development initiatives have been a focus in recent years. This is due, in part, to competency-based training standards and funding sources that reinforce programmatic silos within state and local health departments. National leadership groups representing the specific disciplines within public health were asked to look beyond their discipline-specific priorities and collectively assess the priorities, needs, and characteristics of the governmental public health workforce. The challenges and opportunities facing the public health workforce and crosscutting priority training needs of the public health workforce as a whole were evaluated. Key informant interviews were conducted with 31 representatives from public health member organizations and federal agencies. Interviews were coded and analyzed for major themes. Next, 10 content briefs were created on the basis of priority areas within workforce development. Finally, an in-person priority setting meeting was held to identify top workforce development needs and priorities across all disciplines within public health. Representatives from 31 of 37 invited public health organizations participated, including representatives from discipline-specific member organizations, from national organizations and from federal agencies. Systems thinking, communicating persuasively, change management, information and analytics, problem solving, and working with diverse populations were the major crosscutting areas prioritized. Decades of categorical funding created a highly specialized and knowledgeable workforce that lacks many of the foundational skills now most in demand. The balance between core and specialty training should be reconsidered.

Major Management Challenges and Program Risks: Department of Transportation

DOT National Transportation Integrated Search

2001-01-01

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

Current Challenges in Geothermal Reservoir Simulation

NASA Astrophysics Data System (ADS)

Driesner, T.

2016-12-01

Geothermal reservoir simulation has long been introduced as a valuable tool for geothermal reservoir management and research. Yet, the current generation of simulation tools faces a number of severe challenges, in particular in the application for novel types of geothermal resources such as supercritical reservoirs or hydraulic stimulation. This contribution reviews a number of key problems: Representing the magmatic heat source of high enthalpy resources in simulations. Current practice is representing the deeper parts of a high enthalpy reservoir by a heat flux or temperature boundary condition. While this is sufficient for many reservoir management purposes it precludes exploring the chances of very high enthalpy resources in the deepest parts of such systems as well as the development of reliable conceptual models. Recent 2D simulations with the CSMP++ simulation platform demonstrate the potential of explicitly including the heat source, namely for understanding supercritical resources. Geometrically realistic incorporation of discrete fracture networks in simulation. A growing number of simulation tools can, in principle, handle flow and heat transport in discrete fracture networks. However, solving the governing equations and representing the physical properties are often biased by introducing strongly simplifying assumptions. Including proper fracture mechanics in complex fracture network simulations remains an open challenge. Improvements of the simulating chemical fluid-rock interaction in geothermal reservoirs. Major improvements have been made towards more stable and faster numerical solvers for multicomponent chemical fluid rock interaction. However, the underlying thermodynamic models and databases are unable to correctly address a number of important regions in temperature-pressure-composition parameter space. Namely, there is currently no thermodynamic formalism to describe relevant chemical reactions in supercritical reservoirs. Overcoming this unsatisfactory situation requires fundamental research in high temperature physical chemistry rather than further numerical development.

Major Management Challenges and Program Risks. Department of State

DTIC Science & Technology

2001-01-01

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

Major Management Challenges and Program Risks. Department of the Interior

DTIC Science & Technology

2001-01-01

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

Retention of Underrepresented Minority Faculty: Strategic Initiatives for Institutional Value Proposition Based on Perspectives from a Range of Academic Institutions

PubMed Central

Whittaker, Joseph A.; Montgomery, Beronda L.; Martinez Acosta, Veronica G.

2015-01-01

The student and faculty make-up of academic institutions does not represent national demographics. Racial and ethnic minorities are disproportionately underrepresented nationally, and particularly at predominantly white institutions (PWIs). Although significant efforts and funding have been committed to increasing points of access or recruitment of under-represented minority (URM) students and faculty at PWIs, these individuals have not been recruited and retained at rates that reflect their national proportions. Underrepresentation of URMs is particularly prevalent in Science, Technology, Engineering, and Mathematics (STEM) disciplines. This reality represents a national crisis given a predicted shortage of workers in STEM disciplines based on current rates of training of all individuals, majority and URM, and the intersection of this limitation with persistent challenges in the recruitment, training, retention and advancement of URMs who will soon represent the largest pool of future trainees. An additional compounding factor is the increasingly disproportionate underrepresentation of minorities at higher professorial and administrative ranks, thus limiting the pool of potential mentors who are correlated with successful shepherding of URM students through STEM training and development. We address issues related to improving recruitment and retention of URM faculty that are applicable across a range of academic institutions. We describe challenges with recruitment and retention of URM faculty and their advancement through promotion in the faculty ranks and into leadership positions. We offer specific recommendations, including identifying environmental barriers to diversity and implementing strategies for their amelioration, promoting effective and innovative mentoring, and addressing leadership issues related to constructive change for promoting diversity. PMID:26240521

Retention of Underrepresented Minority Faculty: Strategic Initiatives for Institutional Value Proposition Based on Perspectives from a Range of Academic Institutions.

PubMed

Whittaker, Joseph A; Montgomery, Beronda L; Martinez Acosta, Veronica G

2015-01-01

The student and faculty make-up of academic institutions does not represent national demographics. Racial and ethnic minorities are disproportionately underrepresented nationally, and particularly at predominantly white institutions (PWIs). Although significant efforts and funding have been committed to increasing points of access or recruitment of under-represented minority (URM) students and faculty at PWIs, these individuals have not been recruited and retained at rates that reflect their national proportions. Underrepresentation of URMs is particularly prevalent in Science, Technology, Engineering, and Mathematics (STEM) disciplines. This reality represents a national crisis given a predicted shortage of workers in STEM disciplines based on current rates of training of all individuals, majority and URM, and the intersection of this limitation with persistent challenges in the recruitment, training, retention and advancement of URMs who will soon represent the largest pool of future trainees. An additional compounding factor is the increasingly disproportionate underrepresentation of minorities at higher professorial and administrative ranks, thus limiting the pool of potential mentors who are correlated with successful shepherding of URM students through STEM training and development. We address issues related to improving recruitment and retention of URM faculty that are applicable across a range of academic institutions. We describe challenges with recruitment and retention of URM faculty and their advancement through promotion in the faculty ranks and into leadership positions. We offer specific recommendations, including identifying environmental barriers to diversity and implementing strategies for their amelioration, promoting effective and innovative mentoring, and addressing leadership issues related to constructive change for promoting diversity.

Current Challenges and Future of Lipid nanoparticles formulations for topical drug application to oral mucosa, skin, and eye.

PubMed

Guilherme, Viviane A; Ribeiro, Ligia N M; Tofoli, Giovana Radomille; Franz-Montan, Michelle; de Paula, Eneida; de Jesus, Marcelo Bispo

2017-11-21

Topical drug administration offers an attractive route with minimal invasiveness. It also avoids limitations of intravenous administration such as the first pass metabolism and presystemic elimination within the gastrointestinal tract. Furthermore, topical drug administration is safe, have few side effects, is easy to apply, and offers a fast onset of action. However, the development of effective topical formulations still represents a challenge for the desired effect to be reached, locally or systemically. Solid lipid nanoparticles and nanostructured lipid carriers are particular candidates to overcome the problem of topical drug administration. The nanometric particle size of lipid nanoparticles favors the physical adhesion to the skin or mucosal, what can also be attained with the formation of hybrid (nanoparticles/polymer) systems. In this review, we discuss the major challenges for lipid nanoparticles formulations for topical application to oral mucosa, skin, and eye, highlighting the strategies to improve the performance of lipid nanoparticles for topical applications. Next, we critically analyzed the in vitro and in vivo approaches used to evaluate lipid nanoparticles performance and toxicity. We addressed some major drawbacks related to lipid nanoparticle topical formulations and concluded the key points that have to be overcome to help them to reach the market in topical formulations to oral mucosa, skin and eye. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Back to the basics: Identifying and addressing underlying challenges in achieving high quality and relevant health statistics for indigenous populations in Canada

PubMed Central

Smylie, Janet; Firestone, Michelle

2015-01-01

Canada is known internationally for excellence in both the quality and public policy relevance of its health and social statistics. There is a double standard however with respect to the relevance and quality of statistics for Indigenous populations in Canada. Indigenous specific health and social statistics gathering is informed by unique ethical, rights-based, policy and practice imperatives regarding the need for Indigenous participation and leadership in Indigenous data processes throughout the spectrum of indicator development, data collection, management, analysis and use. We demonstrate how current Indigenous data quality challenges including misclassification errors and non-response bias systematically contribute to a significant underestimate of inequities in health determinants, health status, and health care access between Indigenous and non-Indigenous people in Canada. The major quality challenge underlying these errors and biases is the lack of Indigenous specific identifiers that are consistent and relevant in major health and social data sources. The recent removal of an Indigenous identity question from the Canadian census has resulted in further deterioration of an already suboptimal system. A revision of core health data sources to include relevant, consistent, and inclusive Indigenous self-identification is urgently required. These changes need to be carried out in partnership with Indigenous peoples and their representative and governing organizations. PMID:26793283

Responding to a significant recruitment challenge within three nationwide psychoeducational trials for cancer patients.

PubMed

Stanton, Annette L; Morra, Marion E; Diefenbach, Michael A; Miller, Suzanne M; Slevin Perocchia, Rosemarie; Raich, Peter C; Fleisher, Linda; Wen, Kuang-Yi; Tran, Zung Vu; Mohamed, Nihal E; George, Roshini; Bright, Mary Anne; Marcus, Alfred C

2013-09-01

When faced with a significant recruitment challenge for three nationwide psychoeducational trials targeting prostate and breast cancer patients, the Cancer Information Service Research Consortium initiated outreach efforts to increase accrual. Recruitment is reported by major outreach strategy to inform the use of similar campaigns, either as primary recruitment efforts or to supplement "in-reach" recruitment within oncology settings. During a 33-month period, recruitment was tracked from the National Cancer Institute's Cancer Information Service (CIS), the American Cancer Society (ACS), Dr. Susan Love Research Foundation's Love/Avon Army of Women (AOW), Internet advertising, press releases, radio/television interviews, recruitment materials in community venues, and outreach to churches and cancer support organizations. Across projects, the majority (89 %) of recruited participants (N = 2,134) was obtained from the CIS (n = 901, 19 months of recruitment), AOW (n = 869, 18 months), and ACS (n = 123, 12 months). Other efforts showed minimal gain in recruitment. Cancer information programs (e.g., CIS and ACS) and registries of individuals willing to participate in cancer-related research (e.g., AOW) can represent exceptional resources for outreach recruitment of cancer patients, especially when the eligibility criteria are highly restrictive. However, these resources do not yield samples representative of the larger population of adults diagnosed with cancer, and conclusions from such trials must be tempered accordingly. Inadequate recruitment to randomized controlled trials limits the creation of useful interventions for cancer survivors. By enrolling in cancer registries and taking part in research, cancer survivors can contribute to the development of effective resources for the survivor population.

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

PubMed

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

2017-09-12

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

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

PubMed

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

2017-01-01

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

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

PubMed

Reubi, Jean Claude

2017-12-01

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

Challenges in Timeseries Analysis from Microlensing

NASA Astrophysics Data System (ADS)

Street, R. A.

2017-06-01

Despite a flood of discoveries over the last ~ 20 years, our knowledge of the exoplanet population is incomplete owing to a gap between the sensitivities of different detection techniques. However, a census of exoplanets at all separations from their host stars is essential to fully understand planet formation mechanisms. Microlensing offers an effective way to bridge the gap around 1-10 AU and is therefore one of the major science goals of the Wide Field Infrared Survey Telescope (WFIRST) mission. WFIRST's survey of the Galactic Bulge is expected to discover ~ 20,000 microlensing events, including ~ 3000 planets, which represents a substantial data analysis challenge with the modeling software currently available. This paper highlights areas where further work is needed. The community is encouraged to join new software development efforts aimed at making the modeling of microlensing events both more accessible and rigorous.

A Control Chart Approach for Representing and Mining Data Streams with Shape Based Similarity

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

Omitaomu, Olufemi A

The mining of data streams for online condition monitoring is a challenging task in several domains including (electric) power grid system, intelligent manufacturing, and consumer science. Considering a power grid application in which thousands of sensors, called the phasor measurement units, are deployed on the power grid network to continuously collect streams of digital data for real-time situational awareness and system management. Depending on design, each sensor could stream between ten and sixty data samples per second. The myriad of sensory data captured could convey deeper insights about sequence of events in real-time and before major damages are done. However,more » the timely processing and analysis of these high-velocity and high-volume data streams is a challenge. Hence, a new data processing and transformation approach, based on the concept of control charts, for representing sequence of data streams from sensors is proposed. In addition, an application of the proposed approach for enhancing data mining tasks such as clustering using real-world power grid data streams is presented. The results indicate that the proposed approach is very efficient for data streams storage and manipulation.« less

Training yourself while training students: the constant challenge of vocational training teachers.

PubMed

Chatigny, Céline; Lévesque, Sophie; Riel, Jessica

2012-01-01

This study characterized teachers' work at a vocational training (VT) center and the conditions under which the activity is learned. We interviewed administrators and 12 teachers (4 males, 8 females) representing three study programs, selected as representative (age, seniority, and employment status). What emerged was a portrait of an evolving profession within an organization that was highly structured in terms of the assignment of tasks and schedules, but unstructured in terms of support for job adaptation and job retention. The major challenges for the teachers were to integrate their trade-specific knowledge with the new skills required to teach the trade, and to find time for class preparation. The lack of resources and support caused dissatisfaction, stress, problematic work-study-family balance, and health problems, particularly among new teachers. A passion for teaching seems to compensate partly for these difficulties but it is uncertain for how long. Further research is necessary in order to understand the coping strategies employed by vocational training teachers. The findings of this study offer guidance for the development of resources that can assist with learning and performing the work of a VT teacher, and for a better recognition of the work of VT teachers.

The development of partnership after hypertensive diseases in pregnancy.

PubMed

Leeners, Brigitte; Rath, Werner; Kuse, Sabine; Tschudin, Sibil

2015-04-01

Hypertensive diseases in pregnancy (HDP) occur in 5-8% of all pregnancies and represent one of the most important causes of maternal and fetal morbidity. Even after a normal pregnancy/delivery adaptation to parenthood is a major challenge. However, a successful adjustment is important for future family health. As pregnancy complications may put additional strain on early parenthood, the current study investigated satisfaction with partnership including factors which determine (dis)satisfaction as well as separation rates after pregnancies complicated by HDP. A total of 737 women after HDP and 624 matched-control women completed a self-administered questionnaire on psycho-social factors in the development of HDP. Free-text answers on satisfaction with partnership were analyzed by conceptual analysis. Women with HDP were significantly less often satisfied with their partnership than control women (76%/81.1%; p < 0.05). Women with preeclampsia were at higher risk for an unsatisfactory relationship than those with other manifestations of HDP. Common interests and aims could be identified as the most important reasons for a satisfying marital relationship in women with and without a diagnosis of HDP. HDP represent an additional challenge in family adjustment. Adapted perinatal psycho-social support may help to facilitate the start into family life.

Automated analysis of non-mass-enhancing lesions in breast MRI based on morphological, kinetic, and spatio-temporal moments and joint segmentation-motion compensation technique

NASA Astrophysics Data System (ADS)

Hoffmann, Sebastian; Shutler, Jamie D.; Lobbes, Marc; Burgeth, Bernhard; Meyer-Bäse, Anke

2013-12-01

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) represents an established method for the detection and diagnosis of breast lesions. While mass-like enhancing lesions can be easily categorized according to the Breast Imaging Reporting and Data System (BI-RADS) MRI lexicon, a majority of diagnostically challenging lesions, the so called non-mass-like enhancing lesions, remain both qualitatively as well as quantitatively difficult to analyze. Thus, the evaluation of kinetic and/or morphological characteristics of non-masses represents a challenging task for an automated analysis and is of crucial importance for advancing current computer-aided diagnosis (CAD) systems. Compared to the well-characterized mass-enhancing lesions, non-masses have no well-defined and blurred tumor borders and a kinetic behavior that is not easily generalizable and thus discriminative for malignant and benign non-masses. To overcome these difficulties and pave the way for novel CAD systems for non-masses, we will evaluate several kinetic and morphological descriptors separately and a novel technique, the Zernike velocity moments, to capture the joint spatio-temporal behavior of these lesions, and additionally consider the impact of non-rigid motion compensation on a correct diagnosis.

The Global Phylogeography of Lyssaviruses - Challenging the 'Out of Africa' Hypothesis

PubMed Central

Fooks, Anthony R.; Marston, Denise A.; Garcia-R, Juan C.

2016-01-01

Rabies virus kills tens of thousands of people globally each year, especially in resource-limited countries. Yet, there are genetically- and antigenically-related lyssaviruses, all capable of causing the disease rabies, circulating globally among bats without causing conspicuous disease outbreaks. The species richness and greater genetic diversity of African lyssaviruses, along with the lack of antibody cross-reactivity among them, has led to the hypothesis that Africa is the origin of lyssaviruses. This hypothesis was tested using a probabilistic phylogeographical approach. The nucleoprotein gene sequences from 153 representatives of 16 lyssavirus species, collected between 1956 and 2015, were used to develop a phylogenetic tree which incorporated relevant geographic and temporal data relating to the viruses. In addition, complete genome sequences from all 16 (putative) species were analysed. The most probable ancestral distribution for the internal nodes was inferred using three different approaches and was confirmed by analysis of complete genomes. These results support a Palearctic origin for lyssaviruses (posterior probability = 0.85), challenging the ‘out of Africa’ hypothesis, and suggest three independent transmission events to the Afrotropical region, representing the three phylogroups that form the three major lyssavirus clades. PMID:28036390

Instrumentation development for In Situ 40Ar/39Ar planetary geochronology

USGS Publications Warehouse

Morgan, Leah; Munk, Madicken; Davidheiser-Kroll, Brett; Warner, Nicholas H.; Gupta, Sanjeev; Slaybaugh, Rachel; Harkness, Patrick; Mark, Darren

2017-01-01

The chronology of the Solar System, particularly the timing of formation of extra-terrestrial bodies and their features, is an outstanding problem in planetary science. Although various chronological methods for in situ geochronology have been proposed (e.g., Rb-Sr, K-Ar), and even applied (K-Ar), the reliability, accuracy, and applicability of the 40Ar/39Ar method makes it by far the most desirable chronometer for dating extra-terrestrial bodies. The method however relies on the neutron irradiation of samples, and thus a neutron source. Herein, we discuss the challenges and feasibility of deploying a passive neutron source to planetary surfaces for the in situ application of the 40Ar/39Ar chronometer. Requirements in generating and shielding neutrons, as well as analysing samples are described, along with an exploration of limitations such as mass, power and cost. Two potential solutions for the in situ extra-terrestrial deployment of the 40Ar/39Ar method are presented. Although this represents a challenging task, developing the technology to apply the 40Ar/39Ar method on planetary surfaces would represent a major advance towards constraining the timescale of solar system formation and evolution.

Major Management Challenges and Program Risks. Department of the Treasury

DTIC Science & Technology

2001-01-01

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

Refractory Depressed and Anxious States in Hyperthymic Women: A Case Series Generated by a Speaking Engagement

PubMed Central

Manning, J. Sloan

2000-01-01

The author discusses 4 referrals that were the direct result of a case description from his own practice that he presented during a lecture on the treatment of mixed anxious and depressive illness in primary care. The cases depict energetic, productive women who suffer fatigue and episodic depressions. These cases suggest that hyperthymic temperaments complicated by depressive episodes represent a form of mood disorder presentation that is highly recognizable and responsive to pharmacologic intervention. Such premorbid temperamental hypomanic tendencies may represent a soft form of bipolar illness that requires somatic strategies in line with those of classic manic depressive illness. The cases underscore the challenge of treating mood disorders and the need for treatment research to reach primary care practitioners, who see the majority of depressed and anxious patients. PMID:15014663

Ceritinib for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer.

PubMed

Landi, Lorenza; Cappuzzo, Federico

2016-01-01

Non-small cell lung cancer (NSCLC) represents the paradigm of personalized treatment of human cancer. Several oncogenic druggable alterations have been so far identified, with anaplastic lymphoma kinase (ALK) gene rearrangements representing one of the newest and most appealing. Crizotinib is now recognized as the standard of care in ALK-positive NSCLC due to the positive results of recently published trials. Unfortunately, resistance inevitably occurs within the first year of treatment. Overcoming resistance is the major challenge in clinical oncology, and novel potent ALK inhibitors are currently under evaluation, including ceritinib. Ceritinib is an oral, potent, second-generation ALK inhibitor demonstrating activity in patients who develop resistance to crizotinib. Recent data also suggested efficacy in ALK-inhibitor-naive population, thus supporting investigation of the drug in front-line setting.

The current management of carotid atherosclerotic disease: who, when and how?

PubMed Central

Ritter, Jens C.; Tyrrell, Mark R.

2013-01-01

Ischaemic stroke represents a major health hazard in the western world, which has a severe impact on society and the health-care system. Roughly, 10% of all first ischaemic strokes can be attributed to significant atherosclerotic disease of the carotid arteries. Correct management of these lesions is essential in the prevention and treatment of carotid disease-related ischaemic events. The close relationship between diagnosis and medical and surgical management makes it necessary that all involved physicians and surgeons have profound knowledge of management strategies beyond their specific speciality. Continuous improvement in pharmacological therapy and operative techniques as well as frequently changing guidelines represent a constant challenge for the individual health-care professional. This review gives a thorough outline of the up-to-date evidence-based management of carotid artery disease and discusses its current controversies. PMID:23197661

Major health service transformation and the public voice: conflict, challenge or complicity?

PubMed

Martin, Graham P; Carter, Pam; Dent, Mike

2018-01-01

Objectives Calls for major reconfigurations of health services have been accompanied by recommendations that wide ranging stakeholders be involved. In particular, patients and the wider public are seen as critical contributors as both funders and beneficiaries of public health care. But public involvement is fraught with challenges, and little research has focused on involvement in the health service transformation initiatives. This paper examines the design and function of public involvement in reconfiguration of health services within the English NHS. Methods Qualitative data including interviews, observation and documents were collected in two health service 'transformation' programmes; interviews include involved public and professional participants. Data were analysed using parallel deductive and inductive approaches. Results Public involvement in the programmes was extensive but its terms of reference, and the individuals involved, were restricted by policy pressures and programme objectives. The degree to which participants descriptively or substantively represented the wider public was limited; participants sought to 'speak for' this public but their views on what was 'acceptable' and likely to influence decision-making led them to constrain their contributions. Conclusions Public involvement in two major service reconfiguration programmes in England was seen as important and functional, and could not be characterized as tokenistic. Yet involvement in these programmes fell short of normative ideals, and could inadvertently reduce, rather than enlarge, public influence on health service reconfiguration decisions.

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

Dinh, Nam; Athe, Paridhi; Jones, Christopher

The Virtual Environment for Reactor Applications (VERA) code suite is assessed in terms of capability and credibility against the Consortium for Advanced Simulation of Light Water Reactors (CASL) Verification and Validation Plan (presented herein) in the context of three selected challenge problems: CRUD-Induced Power Shift (CIPS), Departure from Nucleate Boiling (DNB), and Pellet-Clad Interaction (PCI). Capability refers to evidence of required functionality for capturing phenomena of interest while capability refers to the evidence that provides confidence in the calculated results. For this assessment, each challenge problem defines a set of phenomenological requirements against which the VERA software is assessed. Thismore » approach, in turn, enables the focused assessment of only those capabilities relevant to the challenge problem. The evaluation of VERA against the challenge problem requirements represents a capability assessment. The mechanism for assessment is the Sandia-developed Predictive Capability Maturity Model (PCMM) that, for this assessment, evaluates VERA on 8 major criteria: (1) Representation and Geometric Fidelity, (2) Physics and Material Model Fidelity, (3) Software Quality Assurance and Engineering, (4) Code Verification, (5) Solution Verification, (6) Separate Effects Model Validation, (7) Integral Effects Model Validation, and (8) Uncertainty Quantification. For each attribute, a maturity score from zero to three is assigned in the context of each challenge problem. The evaluation of these eight elements constitutes the credibility assessment for VERA.« less

Probing structures of large protein complexes using zero-length cross-linking.

PubMed

Rivera-Santiago, Roland F; Sriswasdi, Sira; Harper, Sandra L; Speicher, David W

2015-11-01

Structural mass spectrometry (MS) is a field with growing applicability for addressing complex biophysical questions regarding proteins and protein complexes. One of the major structural MS approaches involves the use of chemical cross-linking coupled with MS analysis (CX-MS) to identify proximal sites within macromolecules. Identified cross-linked sites can be used to probe novel protein-protein interactions or the derived distance constraints can be used to verify and refine molecular models. This review focuses on recent advances of "zero-length" cross-linking. Zero-length cross-linking reagents do not add any atoms to the cross-linked species due to the lack of a spacer arm. This provides a major advantage in the form of providing more precise distance constraints as the cross-linkable groups must be within salt bridge distances in order to react. However, identification of cross-linked peptides using these reagents presents unique challenges. We discuss recent efforts by our group to minimize these challenges by using multiple cycles of LC-MS/MS analysis and software specifically developed and optimized for identification of zero-length cross-linked peptides. Representative data utilizing our current protocol are presented and discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

“Undiagnosing” multiple sclerosis

PubMed Central

Klein, Eran P.; Bourdette, Dennis

2012-01-01

Objective: To describe the clinical characteristics of encounters with patients misdiagnosed with multiple sclerosis (MS). Methods: A cross-sectional Internet-based physician survey of MS specialists was performed. Results: The response rate for the survey was 50.4%. Of those who responded, the majority (95%) reported having evaluated 1 or more patients who had been diagnosed with MS, but who they strongly felt did not have MS, within the last year. The majority of respondents (>90%) also reported the use of disease-modifying therapy in a proportion of these patients. Most respondents (94%) found clinical encounters with these patients equally or more challenging than giving a new diagnosis of MS. Fourteen percent of respondents reported that they did not always inform such patients of their opinion that they did not have MS. Conclusions: The misdiagnosis of MS is common and has significant consequences for patient care and health care system costs. Caring for a patient with a misdiagnosis of MS is challenging, and at times honest disclosure of a misdiagnosis represents an important ethical concern for neurologists. More data are needed on this patient population to improve diagnostic acumen and the care of these patients. PMID:22581930

Low-cost approaches to problem-driven hydrologic research: The case of Arkavathy watershed, India.

NASA Astrophysics Data System (ADS)

Srinivasan, V.; Ballukraya, P. N.; Jeremiah, K.; R, A.

2014-12-01

Groundwater depletion is a major problem in the Arkavathy Basin and it is the probable cause of declining flows in the Arkavathy River. However, investigating groundwater trends and groundwater-surface water linkages is extremely challenging in a data-scarce environment where basins are largely ungauged so there is very little historical data; often the data are missing, flawed or biased. Moreover, hard-rock aquifer data are very difficult to interpret. In the absence of reliable data, establishing a trend let alone the causal linkages is a severe challenge. We used a combination of low-cost, participatory, satellite based and conventional data collection methods to maximize spatial and temporal coverage of data. For instance, long-term groundwater trends are biased because only a few dug wells with non-representative geological conditions still have water - the vast majority of the monitoring wells drilled in the 1970s and 1980s have dried up. Instead, we relied on "barefoot hydrology" techniques. By conducting a comprehensive well census, engaging farmers in participatory groundwater monitoring and using locally available commercial borewell scanning techniques we have been able to better establish groundwater trends and spatial patterns.

Development of the first infrared satellite observatory

NASA Technical Reports Server (NTRS)

Smith, G. M.; Squibb, G. F.

1984-01-01

A development history is given for the Infrared Astronomical Satelite (IRAS), whose primary mission objective is an unbiased, all-sky survey in the 8-120 micron wavelength range. A point source catalog of more than 200,000 IR sources, to be published later this year, represents the accomplishment of this objective. IRAS has also conducted 10,000 pointed observations of specific objects. Attention is given to the cost increases and schedule slips which resulted from the substantial technical challenges of IRAS hardware and software development, and to the management techniques which had to be employed in this major international project.

Current progress in patient-specific modeling

PubMed Central

2010-01-01

We present a survey of recent advancements in the emerging field of patient-specific modeling (PSM). Researchers in this field are currently simulating a wide variety of tissue and organ dynamics to address challenges in various clinical domains. The majority of this research employs three-dimensional, image-based modeling techniques. Recent PSM publications mostly represent feasibility or preliminary validation studies on modeling technologies, and these systems will require further clinical validation and usability testing before they can become a standard of care. We anticipate that with further testing and research, PSM-derived technologies will eventually become valuable, versatile clinical tools. PMID:19955236

Which are the greatest recent discoveries and the greatest future challenges in nutrition?

PubMed

Katan, M B; Boekschoten, M V; Connor, W E; Mensink, R P; Seidell, J; Vessby, B; Willett, W

2009-01-01

Nutrition science aims to create new knowledge, but scientists rarely sit back to reflect on what nutrition research has achieved in recent decades. We report the outcome of a 1-day symposium at which the audience was asked to vote on the greatest discoveries in nutrition since 1976 and on the greatest challenges for the coming 30 years. Most of the 128 participants were Dutch scientists working in nutrition or related biomedical and public health fields. Candidate discoveries and challenges were nominated by five invited speakers and by members of the audience. Ballot forms were then prepared on which participants selected one discovery and one challenge. A total of 15 discoveries and 14 challenges were nominated. The audience elected Folic acid prevents birth defects as the greatest discovery in nutrition science since 1976. Controlling obesity and insulin resistance through activity and diet was elected as the greatest challenge for the coming 30 years. This selection was probably biased by the interests and knowledge of the speakers and the audience. For the present review, we therefore added 12 discoveries from the period 1976 to 2006 that we judged worthy of consideration, but that had not been nominated at the meeting. The meeting did not represent an objective selection process, but it did demonstrate that the past 30 years have yielded major new discoveries in nutrition and health.

The challenge and prevention of epidemics: experience from offshore petroleum installations and its extrapolation to ships.

PubMed

Ulven, Arne Johan

2011-01-01

The risk of epidemics represents an important challenge in offshore petroleum activities. All personnel are needed for regular operations, and the outbreak of an epidemic will soon affect the operations. The economical consequences can be vast. The risk of an epidemic is raised due to the closeness of living and catering offshore combined with frequent changes of personnel who travel offshore from many nations. The article is based on the experience gained by the author during 22 years as a senior medical officer in a Norwegian oil company. Some endemics and epidemics are described. None of these resulted in the shutdown of production, but they still represented a major challenge to the company and to the medical staff in particular. The transfer value from experience offshore to ships is obvious but there are differences. Risk analysis and quality assurance systems play an important part in the prevention and limitation of epidemics offshore. The infrastructure of the food supply chain as well as education and training of personnel are key elements. Campaigns on different hygiene topics that address all personnel are launched at regular intervals. Contingency plans must be established and be ready for use in case of a threatening epidemic. Identification of the type and source of the infection or food poisoning, isolation of the infected personnel, safe evacuation of patients, and the establishment of other necessary barriers for reduction of spread of infection are necessary to control an outbreak of an epidemic.

Translational new approaches for investigating mood disorders in rodents and what they may reveal about the underlying neurobiology of major depressive disorder

PubMed Central

2018-01-01

Mood disorders represent one of society's most costly and challenging health burdens. The drug treatments used today were initially discovered serendipitously in the 1950s. Animal models were then developed based on the ability of these drugs to alter specific behaviours. These models have played a major role in the development of the second generation of antidepressants. However, their use has been heavily criticized, particularly in relation to whether they recapitulate similar underlying biology to the psychiatric disorder they are proposed to represent. This article considers our work in the field of affective bias and the development of a translational research programme to try to develop and validate better animal models. We discuss whether the new data that have arisen from these studies support an alternative perspective on the underlying neurobiological processes that lead to major depressive disorder (MDD). Specifically, this article will consider whether a neuropsychological mechanism involving affective biases plays a causal role in the development of MDD and its associated emotional and behavioural symptoms. These animal studies also raise the possibility that neuropsychological mechanisms involving affective biases are a precursor to, rather than a consequence of, the neurotrophic changes linked to MDD. This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’. PMID:29352034

Translational new approaches for investigating mood disorders in rodents and what they may reveal about the underlying neurobiology of major depressive disorder.

PubMed

Robinson, Emma S J

2018-03-19

Mood disorders represent one of society's most costly and challenging health burdens. The drug treatments used today were initially discovered serendipitously in the 1950s. Animal models were then developed based on the ability of these drugs to alter specific behaviours. These models have played a major role in the development of the second generation of antidepressants. However, their use has been heavily criticized, particularly in relation to whether they recapitulate similar underlying biology to the psychiatric disorder they are proposed to represent. This article considers our work in the field of affective bias and the development of a translational research programme to try to develop and validate better animal models. We discuss whether the new data that have arisen from these studies support an alternative perspective on the underlying neurobiological processes that lead to major depressive disorder (MDD). Specifically, this article will consider whether a neuropsychological mechanism involving affective biases plays a causal role in the development of MDD and its associated emotional and behavioural symptoms. These animal studies also raise the possibility that neuropsychological mechanisms involving affective biases are a precursor to, rather than a consequence of, the neurotrophic changes linked to MDD.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'. © 2018 The Authors.

Anaplastology in times of facial transplantation: Still a reasonable treatment option?

PubMed

Toso, Sabine Maria; Menzel, Kerstin; Motzkus, Yvonne; Klein, Martin; Menneking, Horst; Raguse, Jan-Dirk; Nahles, Susanne; Hoffmeister, Bodo; Adolphs, Nicolai

2015-09-01

Optimum functional and aesthetic facial reconstruction is still a challenge in patients who suffer from inborn or acquired facial deformity. It is known that functional and aesthetic impairment can result in significant psychosocial strain, leading to the social isolation of patients who are affected by major facial deformities. Microvascular techniques and increasing experience in facial transplantation certainly contribute to better restorative outcomes. However, these technologies also have some drawbacks, limitations and unsolved problems. Extensive facial defects which include several aesthetic units and dentition can be restored by combining dental prostheses and anaplastology, thus providing an adequate functional and aesthetic outcome in selected patients without the drawbacks of major surgical procedures. Referring to some representative patient cases, it is shown how extreme facial disfigurement after oncological surgery can be palliated by combining intraoral dentures with extraoral facial prostheses using individualized treatment and without the need for major reconstructive surgery. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Unusual causes of abdominal pain: sickle cell anemia.

PubMed

Ahmed, Shahid; Shahid, Rabia K; Russo, Linda A

2005-04-01

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crises. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestation of the disease. Abdominal pain is an important component of vaso-occlusive painful crises. It often represents a substantial diagnostic challenge in this population of patients. These episodes are often attributed to micro-vessel occlusion and infarcts of mesentery and abdominal viscera. Abdominal pain due to sickle cell vaso-occlusive crisis is often indistinguishable from an acute intra-abdominal disease process such as acute cholecystitis, acute pancreatitis, hepatic infarction, ischemic colitis and acute appendicitis. In the majority of cases, however, no specific cause is identified and spontaneous resolution occurs. This chapter will focus on etiologies, pathophysiology and management of abdominal pain in patients with sickle cell disease.

Summary of sessions on nuclear astrophysics

NASA Astrophysics Data System (ADS)

Rolfs, C.

In the minds of some there exists the patronizing belief that nuclear physics is a mature science. The same is not believed about nuclear astrophysics, which has been an active branch of astrophysics for over fifty years, but is now in the midst of an exciting revival in experimental and theoretical research around the world. The ultimate goal is to understand how nuclear processes generate the energy of stars over their lifetimes and, in doing so, synthesize heavier elements from the primordial hydrogen and helium produced in the Big Bang, which led to the expanding universe. Impressive progress has been made in this goal and this was rewarded. However, there are major puzzles, such as the solar neutrino problem to name just one, which challenge the fundaments of the field. To solve these problems, new nuclear physics data are needed employing novel experimental techniques such as radioactive ion beams and underground accelerator facilities. Without such new data, much of the work done so far will - in an optimistic view - be incomplete and - in a pessimistic view - be possibly wrong. Thus, new data do not represent a fine structure information or a cleaning-up job, but they represent the major next step in this exciting field&

Biomonitoring of intermittent rivers and ephemeral streams in Europe: Current practice and priorities to enhance ecological status assessments.

PubMed

Stubbington, Rachel; Chadd, Richard; Cid, Núria; Csabai, Zoltán; Miliša, Marko; Morais, Manuela; Munné, Antoni; Pařil, Petr; Pešić, Vladimir; Tziortzis, Iakovos; Verdonschot, Ralf C M; Datry, Thibault

2018-03-15

Intermittent rivers and ephemeral streams (IRES) are common across Europe and dominate some Mediterranean river networks. In all climate zones, IRES support high biodiversity and provide ecosystem services. As dynamic ecosystems that transition between flowing, pool, and dry states, IRES are typically poorly represented in biomonitoring programmes implemented to characterize EU Water Framework Directive ecological status. We report the results of a survey completed by representatives from 20 European countries to identify current challenges to IRES status assessment, examples of best practice, and priorities for future research. We identify five major barriers to effective ecological status classification in IRES: 1. the exclusion of IRES from Water Framework Directive biomonitoring based on their small catchment size; 2. the lack of river typologies that distinguish between contrasting IRES; 3. difficulties in defining the 'reference conditions' that represent unimpacted dynamic ecosystems; 4. classification of IRES ecological status based on lotic communities sampled using methods developed for perennial rivers; and 5. a reliance on taxonomic characterization of local communities. Despite these challenges, we recognize examples of innovative practice that can inform modification of current biomonitoring activity to promote effective IRES status classification. Priorities for future research include reconceptualization of the reference condition approach to accommodate spatiotemporal fluctuations in community composition, and modification of indices of ecosystem health to recognize both taxon-specific sensitivities to intermittence and dispersal abilities, within a landscape context. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Implantable brain computer interface: challenges to neurotechnology translation.

PubMed

Konrad, Peter; Shanks, Todd

2010-06-01

This article reviews three concepts related to implantable brain computer interface (BCI) devices being designed for human use: neural signal extraction primarily for motor commands, signal insertion to restore sensation, and technological challenges that remain. A significant body of literature has occurred over the past four decades regarding motor cortex signal extraction for upper extremity movement or computer interface. However, little is discussed regarding postural or ambulation command signaling. Auditory prosthesis research continues to represent the majority of literature on BCI signal insertion. Significant hurdles continue in the technological translation of BCI implants. These include developing a stable neural interface, significantly increasing signal processing capabilities, and methods of data transfer throughout the human body. The past few years, however, have provided extraordinary human examples of BCI implant potential. Despite technological hurdles, proof-of-concept animal and human studies provide significant encouragement that BCI implants may well find their way into mainstream medical practice in the foreseeable future.

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.

The management of large cabling campaigns during the Long Shutdown 1 of LHC

NASA Astrophysics Data System (ADS)

Meroli, S.; Machado, S.; Formenti, F.; Frans, M.; Guillaume, J. C.; Ricci, D.

2014-03-01

The Large Hadron Collider at CERN entered into its first 18 month-long shutdown period in February 2013. During this period the entire CERN accelerator complex will undergo major consolidation and upgrade works, preparing the machines for LHC operation at nominal energy (7 TeV/beam). One of the most challenging activities concerns the cabling infrastructure (copper and optical fibre cables) serving the CERN data acquisition, networking and control systems. About 1000 kilometres of cables, distributed in different machine areas, will be installed, representing an investment of about 15 MCHF. This implies an extraordinary challenge in terms of project management, including resource and activity planning, work execution and quality control. The preparation phase of this project started well before its implementation, by defining technical solutions and setting financial plans for staff recruitment and material supply. Enhanced task coordination was further implemented by deploying selected competences to form a central support team.

Millennium Development Goals 4 and 5: progress and challenges.

PubMed

Bryce, Jennifer; Black, Robert E; Victora, Cesar G

2013-10-16

The Millennium Development Goals have galvanized efforts to improve child survival (MDG-4) and maternal health (MDG-5). There has been important progress on both MDGs at global level, although it now appears that few countries will reach them by the target date of 2015. There are known and efficacious interventions to address most of the major causes of these deaths, but important gaps remain. The biggest challenge is to ensure that all women and children have access to life-saving interventions. Current levels of intervention coverage are too low, representing missed opportunities. Providing services at the community level is an important emerging priority, but preventing maternal and neonatal deaths also requires access to health facilities. Readers of the Medicine for Global Health collection in BMC Medicine are urged to make maternal and child health one of their key concerns, even if they work on other topics.

High-Capacity Hydrogen-Based Green-Energy Storage Solutions For The Grid Balancing

NASA Astrophysics Data System (ADS)

D'Errico, F.; Screnci, A.

One of the current main challenges in green-power storage and smart grids is the lack of effective solutions for accommodating the unbalance between renewable energy sources, that offer intermittent electricity supply, and a variable electricity demand. Energy management systems have to be foreseen for the near future, while they still represent a major challenge. Integrating intermittent renewable energy sources, by safe and cost-effective energy storage systems based on solid state hydrogen is today achievable thanks to recently some technology breakthroughs. Optimized solid storage method made of magnesium-based hydrides guarantees a very rapid absorption and desorption kinetics. Coupled with electrolyzer technology, high-capacity storage of green-hydrogen is therefore practicable. Besides these aspects, magnesium has been emerging as environmentally friend energy storage method to sustain integration, monitoring and control of large quantity of GWh from high capacity renewable generation in the EU.

High-Capacity Hydrogen-Based Green-Energy Storage Solutions for the Grid Balancing

NASA Astrophysics Data System (ADS)

D'Errico, F.; Screnci, A.

One of the current main challenges in green-power storage and smart grids is the lack of effective solutions for accommodating the unbalance between renewable energy sources, that offer intermittent electricity supply, and a variable electricity demand. Energy management systems have to be foreseen for the near future, while they still represent a major challenge. Integrating intermittent renewable energy sources, by safe and cost-effective energy storage systems based on solid state hydrogen is today achievable thanks to recently some technology breakthroughs. Optimized solid storage method made of magnesium-based hydrides guarantees a very rapid absorption and desorption kinetics. Coupled with electrolyzer technology, high-capacity storage of green-hydrogen is therefore practicable. Besides these aspects, magnesium has been emerging as environmentally friend energy storage method to sustain integration, monitoring and control of large quantity of GWh from high capacity renewable generation in the EU.

Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer.

PubMed

Denby, Charles M; Li, Rachel A; Vu, Van T; Costello, Zak; Lin, Weiyin; Chan, Leanne Jade G; Williams, Joseph; Donaldson, Bryan; Bamforth, Charles W; Petzold, Christopher J; Scheller, Henrik V; Martin, Hector Garcia; Keasling, Jay D

2018-03-20

Flowers of the hop plant provide both bitterness and "hoppy" flavor to beer. Hops are, however, both a water and energy intensive crop and vary considerably in essential oil content, making it challenging to achieve a consistent hoppy taste in beer. Here, we report that brewer's yeast can be engineered to biosynthesize aromatic monoterpene molecules that impart hoppy flavor to beer by incorporating recombinant DNA derived from yeast, mint, and basil. Whereas metabolic engineering of biosynthetic pathways is commonly enlisted to maximize product titers, tuning expression of pathway enzymes to affect target production levels of multiple commercially important metabolites without major collateral metabolic changes represents a unique challenge. By applying state-of-the-art engineering techniques and a framework to guide iterative improvement, strains are generated with target performance characteristics. Beers produced using these strains are perceived as hoppier than traditionally hopped beers by a sensory panel in a double-blind tasting.

Affordances and Alignments: Continuing Challenges in Advising Undergraduate Psychology Majors

ERIC Educational Resources Information Center

Landrum, R. Eric

2018-01-01

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

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

PubMed

Halim, Abdel-Baset

2015-06-01

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

Relaunching a national social marketing campaign: expectations and challenges for the "new" ParticipACTION.

PubMed

Faulkner, Guy; McCloy, Cora; Plotnikoff, Ronald C; Tremblay, Mark S

2011-07-01

ParticipACTION is a Canadian physical activity communications and social marketing organization that has been relaunched in 2007 after a 6-year hiatus. The purpose of this study is to qualitatively identify and describe the expectations and challenges the relaunch of the new ParticipACTION may present for existing physical activity organizations. Using a purposeful sampling strategy, the authors conduct semistructured telephone interviews with 49 key informants representing a range of national, provincial, and local organizations with a mandate to promote physical activity. Overall, there is strong support in seeing ParticipACTION relaunched. However, organizational expectations and/or their ideal vision for it are mixed. Organizations envision and support its performing an overarching social marketing and advocacy role, and in providing tools and resources that supplement existing organizational activities. Four major organizational challenges are identified concerning overlapping mandates, partnership and leadership concerns, competition for funding, and capacity concerns. Social marketing initiatives, such as ParticipACTION, may not be able to maximize their impact unless they address the expectations and concerns of competing organizations with a mandate to promote physical activity.

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

PubMed

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

Establishing protection networks to ensure that biodiversity and associated ecosystem services persist under changing environments is a major challenge for conservation planning. The potential consequences of altered climates for the structure and function of ecosystems necessitates new and complementary approaches be incorporated into traditional conservation plans. The conterminous United States of America (CONUS) has an extensive system of protected areas managed by federal agencies, but a comprehensive assessment of how this network represents CONUS climate is lacking. We present a quantitative classification of the climate space that is independent from the geographic locations to evaluate the climatic representation of the existing protected area network. We use this classification to evaluate the coverage of each agency's jurisdiction and to identify current conservation deficits. Our findings reveal that the existing network poorly represents CONUS climatic diversity. Although rare climates are generally well represented by the network, the most common climates are particularly underrepresented. Overall, 83% of the area of the CONUS corresponds to climates underrepresented by the network. The addition of some currently unprotected federal lands to the network would enhance the coverage of CONUS climates. However, to fully palliate current conservation deficits, large-scale private-land conservation initiatives will be critical.

Negative correlation between rates of molecular evolution and flowering cycles in temperate woody bamboos revealed by plastid phylogenomics.

PubMed

Ma, Peng-Fei; Vorontsova, Maria S; Nanjarisoa, Olinirina Prisca; Razanatsoa, Jacqueline; Guo, Zhen-Hua; Haevermans, Thomas; Li, De-Zhu

2017-12-21

Heterogeneous rates of molecular evolution are universal across the tree of life, posing challenges for phylogenetic inference. The temperate woody bamboos (tribe Arundinarieae, Poaceae) are noted for their extremely slow molecular evolutionary rates, supposedly caused by their mysterious monocarpic reproduction. However, the correlation between substitution rates and flowering cycles has not been formally tested. Here we present 15 newly sequenced plastid genomes of temperate woody bamboos, including the first genomes ever sequenced from Madagascar representatives. A data matrix of 46 plastid genomes representing all 12 lineages of Arundinarieae was assembled for phylogenetic and molecular evolutionary analyses. We conducted phylogenetic analyses using different sequences (e.g., coding and noncoding) combined with different data partitioning schemes, revealing conflicting relationships involving internodes among several lineages. A great difference in branch lengths were observed among the major lineages, and topological inconsistency could be attributed to long-branch attraction (LBA). Using clock model-fitting by maximum likelihood and Bayesian approaches, we furthermore demonstrated extensive rate variation among these major lineages. Rate accelerations mainly occurred for the isolated lineages with limited species diversification, totaling 11 rate shifts during the tribe's evolution. Using linear regression analysis, we found a negative correlation between rates of molecular evolution and flowering cycles for Arundinarieae, notwithstanding that the correlation maybe insignificant when taking the phylogenetic structure into account. Using the temperate woody bamboos as an example, we found further evidence that rate heterogeneity is universal in plants, suggesting that this will pose a challenge for phylogenetic reconstruction of bamboos. The bamboos with longer flowering cycles tend to evolve more slowly than those with shorter flowering cycles, in accordance with a putative generation time effect.

Crop immunity against viruses: outcomes and future challenges

PubMed Central

Nicaise, Valérie

2014-01-01

Viruses cause epidemics on all major cultures of agronomic importance, representing a serious threat to global food security. As strict intracellular pathogens, they cannot be controlled chemically and prophylactic measures consist mainly in the destruction of infected plants and excessive pesticide applications to limit the population of vector organisms. A powerful alternative frequently employed in agriculture relies on the use of crop genetic resistances, approach that depends on mechanisms governing plant–virus interactions. Hence, knowledge related to the molecular bases of viral infections and crop resistances is key to face viral attacks in fields. Over the past 80 years, great advances have been made on our understanding of plant immunity against viruses. Although most of the known natural resistance genes have long been dominant R genes (encoding NBS-LRR proteins), a vast number of crop recessive resistance genes were cloned in the last decade, emphasizing another evolutive strategy to block viruses. In addition, the discovery of RNA interference pathways highlighted a very efficient antiviral system targeting the infectious agent at the nucleic acid level. Insidiously, plant viruses evolve and often acquire the ability to overcome the resistances employed by breeders. The development of efficient and durable resistances able to withstand the extreme genetic plasticity of viruses therefore represents a major challenge for the coming years. This review aims at describing some of the most devastating diseases caused by viruses on crops and summarizes current knowledge about plant–virus interactions, focusing on resistance mechanisms that prevent or limit viral infection in plants. In addition, I will discuss the current outcomes of the actions employed to control viral diseases in fields and the future investigations that need to be undertaken to develop sustainable broad-spectrum crop resistances against viruses. PMID:25484888

Responding to a Significant Recruitment Challenge within Three Nationwide Psycho-Educational Trials for Cancer Patients

PubMed Central

Stanton, Annette L.; Morra, Marion E.; Miller, Suzanne M.; Diefenbach, Michael A.; Slevin-Perocchia, Rosemarie; Raich, Peter C.; Fleisher, Linda; Wen, Kuang-Yi; Tran, Zung Vu; Mohamed, Nihal E.; George, Roshini; Bright, Mary Anne; Marcus, Alfred C.

2013-01-01

Purpose When faced with a significant recruitment challenge for three nationwide psycho-educational trials targeting prostate and breast cancer patients, the Cancer Information Service Research Consortium initiated outreach efforts to increase accrual. Recruitment is reported by major outreach strategy to inform the use of similar campaigns, either as primary recruitment efforts or to supplement “in-reach” recruitment within oncology settings. Methods During a 33-month period, recruitment was tracked from the National Cancer Institute’s Cancer Information Service (CIS), the American Cancer Society (ACS), Dr. Susan Love Research Foundation’s Love/Avon Army of Women (AOW), Internet advertising, press releases, radio/television interviews, recruitment materials in community venues, and outreach to churches and cancer support organizations. Results Across projects, the majority (89%) of recruited participants (N = 2,134) was obtained from the CIS (n = 901, 19 months of recruitment), AOW (n = 869, 18 months), and ACS (n = 123, 12 months). Other efforts showed minimal gain in recruitment. Conclusions Cancer information programs (e.g., CIS, ACS) and registries of individuals willing to participate in cancer-related research (e.g., AOW) can represent exceptional resources for outreach recruitment of cancer patients, especially when the eligibility criteria are highly restrictive. However, these resources do not yield samples representative of the larger population of adults diagnosed with cancer, and conclusions from such trials must be tempered accordingly. Implications for cancer survivors Inadequate recruitment to randomized controlled trials limits the creation of useful interventions for cancer survivors. By enrolling in cancer registries and taking part in research, cancer survivors can contribute to the development of effective resources for the survivor population. PMID:23595235

Virtual screening of integrase inhibitors by large scale binding free energy calculations: the SAMPL4 challenge

PubMed Central

Gallicchio, Emilio; Deng, Nanjie; He, Peng; Wickstrom, Lauren; Perryman, Alexander L.; Santiago, Daniel N.; Forli, Stefano; Olson, Arthur J.; Levy, Ronald M.

2014-01-01

As part of the SAMPL4 blind challenge, filtered AutoDock Vina ligand docking predictions and large scale binding energy distribution analysis method binding free energy calculations have been applied to the virtual screening of a focused library of candidate binders to the LEDGF site of the HIV integrase protein. The computational protocol leveraged docking and high level atomistic models to improve enrichment. The enrichment factor of our blind predictions ranked best among all of the computational submissions, and second best overall. This work represents to our knowledge the first example of the application of an all-atom physics-based binding free energy model to large scale virtual screening. A total of 285 parallel Hamiltonian replica exchange molecular dynamics absolute protein-ligand binding free energy simulations were conducted starting from docked poses. The setup of the simulations was fully automated, calculations were distributed on multiple computing resources and were completed in a 6-weeks period. The accuracy of the docked poses and the inclusion of intramolecular strain and entropic losses in the binding free energy estimates were the major factors behind the success of the method. Lack of sufficient time and computing resources to investigate additional protonation states of the ligands was a major cause of mispredictions. The experiment demonstrated the applicability of binding free energy modeling to improve hit rates in challenging virtual screening of focused ligand libraries during lead optimization. PMID:24504704

A "Carbon Reduction Challenge" as tool for undergraduate engagement on climate change

NASA Astrophysics Data System (ADS)

Cobb, K. M.; Toktay, B.

2017-12-01

Institutions of higher education must meet the challenges of educating the generation that must make significant progress towards stabilizing atmospheric greenhouse gases. However, the interdisciplinary nature of the climate change problem, and the fact that solutions will necessarily involve manipulating natural systems, advancing energy technologies, and developing innovative policy instruments means that traditional disciplinary tracks are not well-suited for the task. Furthermore, institutions must not only equip students with fundamental knowledge about climate and energy, but they must empower a generation of students to become part of the climate change solution. Here we present the cumulative results of the `Carbon Reduction Challenge' - a team-based competition to reduce CO2 that is conducted in an interdisciplinary undergraduate class called "Energy, the Environment, and Society" at Georgia Institute of Technology. Working with 30 undergraduate students from all years and all majors, we demonstrate how student teams move through a highly-structured timeline of deliverables towards achieving their team's end-of-semester goals. We discuss the importance of student creativity, ingenuity, initiative, and perseverance in achieving project outcomes, which in 2017 topped 5 million pounds of CO2 reductions - the all-time record for the class. Student-driven reductions on a year-to-year basis track an exponential growth curve through time. Based on the success of a pilot Carbon Reduction Challenge conducted in the summer of 2017, we present evidence that student-led partnerships with large corporations represents the area of largest potential for student success. Such partnerships deliver significant value added to students (professional conduct, on-the-job training, networking), the corporate partner (cost savings, talent recruitment, and public relations), and to the higher education institution (corporate relations contacts). In summary, the Carbon Reduction Challenge represents a solutions-oriented, hands-on, project-based learning tool that has achieved significant pedagogical benefits while delivering real-world carbon reductions and cost savings to community stakeholders.

The California Health Interview Survey 2001: translation of a major survey for California's multiethnic population.

PubMed

Ponce, Ninez A; Lavarreda, Shana Alex; Yen, Wei; Brown, E Richard; DiSogra, Charles; Satter, Delight E

2004-01-01

The cultural and linguistic diversity of the U.S. population presents challenges to the design and implementation of population-based surveys that serve to inform public policies. Information derived from such surveys may be less than representative if groups with limited or no English language skills are not included. The California Health Interview Survey (CHIS), first administered in 2001, is a population-based health survey of more than 55,000 California households. This article describes the process that the designers of CHIS 2001 underwent in culturally adapting the survey and translating it into an unprecedented number of languages: Spanish, Chinese, Vietnamese, Korean, and Khmer. The multiethnic and multilingual CHIS 2001 illustrates the importance of cultural and linguistic adaptation in raising the quality of population-based surveys, especially when the populations they intend to represent are as diverse as California's.

Hypoxia inducible factor (HIF) as a model for studying inhibition of protein–protein interactions

PubMed Central

Burslem, George M.; Kyle, Hannah F.; Nelson, Adam; Edwards, Thomas A.

2017-01-01

The modulation of protein–protein interactions (PPIs) represents a major challenge in modern chemical biology. Current approaches (e.g. high-throughput screening, computer aided ligand design) are recognised as having limitations in terms of identification of hit matter. Considerable success has been achieved in terms of developing new approaches to PPI modulator discovery using the p53/hDM2 and Bcl-2 family of PPIs. However these important targets in oncology might be considered as “low-hanging-fruit”. Hypoxia inducible factor (HIF) is an emerging, but not yet fully validated target for cancer chemotherapy. Its role is to regulate the hypoxic response and it does so through a plethora of protein–protein interactions of varying topology, topography and complexity: its modulation represents an attractive approach to prevent development of new vasculature by hypoxic tumours. PMID:28878873

[Thyroid orbitopathy, an overview with special attention to the role of radiotherapy].

PubMed

Vilar-González, Santiago; Lamas-Oliveira, Cristina; Fagúndez-Vargas, María A; Núñez-Quintanilla, Ana T; Pérez-Rozos, Alberto; Merayo-Lloves, Jesús; Escobar-Barranco, José J; Rico-Pérez, José M

2015-04-01

Thyroid orbitopathy is the most prevalent non-thyroid symptom in Graves' syndrome. It has a high incidence and particularly affects young women. Smoking is clearly involved in its development and progress, and in its response to different treatments. This autoimmune condition usually has a benign course, independent from hyperthyroidism, but its severe, progressive forms represent a major therapeutic challenge. Clinical evaluation poses great difficulties, as there is no truly objective rating scale representing disease activity. New molecular or inflammation markers may prove to be useful in this regard. This review reports new findings about its pathophysiology and the different techniques used for treatment over time. Discussion particularly focuses on the immunomodulatory role of radiotherapy, as well as on its role together with corticosteroids. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Brain delivery research in public-private partnerships: The IMI-JU COMPACT consortium as an example.

PubMed

Meyer, Axel H; Untucht, Christopher; Terstappen, Georg C

2017-07-01

The Blood-Brain Barrier (BBB) represents a major hurdle in the development of treatments for CNS disorders due to the fact that it very effectively keeps drugs, especially biological macromolecules, out of the brain. Concomitantly with the increasing importance of biologics research on the BBB and, more specifically, on brain delivery technologies has intensified in recent years. Public-Private Partnerships (PPPs) represent an innovative opportunity to address such complex challenges as they bring together the best expertise from both industry and academia. Here we present the IMI-JU COMPACT (Collaboration on the Optimisation of Macromolecular Pharmaceutical Access to Cellular Targets) consortium working on nanocarriers for targeted delivery of macromolecules as an example. The scope of the consortium, its goals and the expertise within the consortium are outlined. This article is part of the Special Issue entitled "Beyond small molecules for neurological disorders". Copyright © 2016 Elsevier Ltd. All rights reserved.

Cultivating Diversity and Competency in STEM: Challenges and Remedies for Removing Virtual Barriers to Constructing Diverse Higher Education Communities of Success.

PubMed

Whittaker, Joseph A; Montgomery, Beronda L

2012-01-01

The need to increase the number of college graduates in Science, Technology, Engineering, and Mathematics (STEM) disciplines is a national issue. As the demographics of the United States' population grow increasingly more diverse, the recognition that students of color are disproportionately under-represented among those individuals successful at completing STEM degrees requires exigent and sustained intervention. Although a range of efforts and funding have been committed to increasing the success of under-represented minority (URM) students at primarily white, or majority, institutions, widespread progress has been slow. Simultaneously, Historically Black Colleges and Universities and Minority Serving Institutions have demonstrated disproportionate successes in graduating URM students with STEM degrees and those that proceed to completing graduate-level degrees in the sciences. The differential successes of particular institutions with promoting the achievement of diverse individuals in obtaining academic STEM degrees suggest that with committed and strategic leadership, advancements in creating academic communities that promote the success of a diverse range of students in STEM can be achieved in part through assessing and mitigating environmental barriers that impede success at majority institutions. In this paper, we address issues related to the engagement of URM students in majority settings and describe some efforts that have shown success for promoting diversity in STEM and highlight continuing issues and factors associated with cultivating diversity in academic STEM disciplines at majority institutions. Recommended efforts include addressing academic assistance, professional and cultural socialization issues and institutional environmental factors that are associated with success or lack thereof for URMs in STEM.

Major Management Challenges and Program Risks. Department of Labor

DTIC Science & Technology

2001-01-01

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

Multiyear Program Plan for the High Temperature Materials Laboratory

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

Arvid E. Pasto

2000-03-17

Recently, the U.S. Department of Energy's (DOE) Office of Heavy Vehicle Technologies (OHVT) prepared a Technology Roadmap describing the challenges facing development of higher fuel efficiency, less polluting sport utility vehicles, vans, and commercial trucks. Based on this roadmap, a multiyear program plan (MYPP) was also developed, in which approaches to solving the numerous challenges are enumerated. Additional planning has been performed by DOE and national laboratory staff, on approaches to solving the numerous challenges faced by heavy vehicle system improvements. Workshops and planning documents have been developed concerning advanced aerodynamics, frictional and other parasitic losses, and thermal management. Similarly,more » the Heavy Vehicle Propulsion Materials Program has developed its own multiyear program plan. The High Temperature Materials Laboratory, a major user facility sponsored by OHVT, has now developed its program plan, described herein. Information was gathered via participation in the development of OHVT's overall Technology Roadmap and MYPP, through personal contacts within the materials-user community, and from attendance at conferences and expositions. Major materials issues for the heavy vehicle industry currently center on trying to increase efficiency of (diesel) engines while at the same time reducing emissions (particularly NO{sub x} and particulates). These requirements dictate the use of increasingly stronger, higher-temperature capable and more corrosion-resistant materials of construction, as well as advanced catalysts, particulate traps, and other pollution-control devices. Exhaust gas recirculation (EGR) is a technique which will certainly be applied to diesel engines in the near future, and its use represents a formidable challenge, as will be described later. Energy-efficient, low cost materials processing methods and surface treatments to improve wear, fracture, and corrosion resistance are also required.« less

Graph clustering techniques applied to the glycomic response in glioblastoma cells to treatments with STAT3 phosphorylation inhibition and fetal bovine serum

NASA Astrophysics Data System (ADS)

Görke, Robert; Meyer-Bäse, Anke; Plant, Claudia; He, Huan; Emmett, Mark R.; Nilsson, Carol; Colman, Howard; Conrad, Charles A.

2011-06-01

Cancer stem cells (CSC) represent a very small percentage of the total tumor population however they pose a big challenge in treating cancer. Glycans play a key role in cancer therapeutics since overexpression of them depending on the glycan type can lead either to cell death or more invasive metastasis. Two major components, fetal bovine serum (FBS) and STAT3, are known to up- or down-regulate certain glycolipid or phospholipid compositions found in glioblastoma CSCs. The analysis and the understanding of the global interactional behavior of lipidomic networks remains a challenging task and can not be accomplished solely based on intuitive reasoning. The present contribution aims at applying graph clustering networks to analyze the functional aspects of certain activators or inhibitors at the molecular level in glioblastoma stem cells (GSCs). This research enhances our understanding of the differences in phenotype changes and determining the responses of glycans to certain treatments for the aggressive GSCs, and represents together with a quantitative phosphoproteomic study1 the most detailed systems biology study of GSCs differentiation known so far. Thus, these new paradigms are providing unique understanding of the mechanisms involved in GSC maintenance and tumorigenicity and are thus opening a new window to biomedical frontiers.

High Energy Astrophysics Mission

NASA Technical Reports Server (NTRS)

White, Nicholas E.; Ormes, Jonathan F. (Technical Monitor)

2000-01-01

The nature of gravity and its relationship to the other three forces and to quantum theory is one of the major challenges facing us as we begin the new century. In order to make progress we must challenge the current theories by observing the effects of gravity under the most extreme conditions possible. Black holes represent one extreme, where the laws of physics as we understand them break down. The Universe as whole is another extreme, where its evolution and fate is dominated by the gravitational influence of dark matter and the nature of the Cosmological constant. The early universe represents a third extreme, where it is thought that gravity may somehow be unified with the other forces. NASA's "Cosmic Journeys" program is part of a NASA/NSF/DoE tri-agency initiative designed to observe the extremes of gravity throughout the universe. This program will probe the nature of black holes, ultimately obtaining a direct image of the event horizon. It will investigate the large scale structure of the Universe to constrain the location and nature of dark matter and the nature of the cosmological constant. Finally it will search for and study the highest energy processes, that approach those found in the early universe. I will outline the High Energy Astrophysics part of this program.

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.

BA71ΔCD2: a New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities.

PubMed

Monteagudo, Paula L; Lacasta, Anna; López, Elisabeth; Bosch, Laia; Collado, Javier; Pina-Pedrero, Sonia; Correa-Fiz, Florencia; Accensi, Francesc; Navas, María Jesús; Vidal, Enric; Bustos, María J; Rodríguez, Javier M; Gallei, Andreas; Nikolin, Veljko; Salas, María L; Rodríguez, Fernando

2017-11-01

African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71ΔCD2 to induce specific CD8 + T cells capable of recognizing both BA71 and E75 viruses in vitro Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating. IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe. Copyright © 2017 Monteagudo et al.

BA71ΔCD2: a New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities

PubMed Central

Monteagudo, Paula L.; Lacasta, Anna; López, Elisabeth; Bosch, Laia; Collado, Javier; Pina-Pedrero, Sonia; Correa-Fiz, Florencia; Accensi, Francesc; Navas, María Jesús; Vidal, Enric; Bustos, María J.; Rodríguez, Javier M.; Gallei, Andreas; Nikolin, Veljko; Salas, María L.

2017-01-01

ABSTRACT African swine fever is a highly contagious viral disease of mandatory declaration to the World Organization for Animal Health (OIE). The lack of available vaccines makes its control difficult; thus, African swine fever virus (ASFV) represents a major threat to the swine industry. Inactivated vaccines do not confer solid protection against ASFV. Conversely, live attenuated viruses (LAV), either naturally isolated or obtained by genetic manipulation, have demonstrated reliable protection against homologous ASFV strains, although little or no protection has been demonstrated against heterologous viruses. Safety concerns are a major issue for the use of ASFV attenuated vaccine candidates and have hampered their implementation in the field so far. While trying to develop safer and efficient ASFV vaccines, we found that the deletion of the viral CD2v (EP402R) gene highly attenuated the virulent BA71 strain in vivo. Inoculation of pigs with the deletion mutant virus BA71ΔCD2 conferred protection not only against lethal challenge with the parental BA71 but also against the heterologous E75 (both genotype I strains). The protection induced was dose dependent, and the cross-protection observed in vivo correlated with the ability of BA71ΔCD2 to induce specific CD8+ T cells capable of recognizing both BA71 and E75 viruses in vitro. Interestingly, 100% of the pigs immunized with BA71ΔCD2 also survived lethal challenge with Georgia 2007/1, the genotype II strain of ASFV currently circulating in continental Europe. These results open new avenues to design ASFV cross-protective vaccines, essential to fight ASFV in areas where the virus is endemic and where multiple viruses are circulating. IMPORTANCE African swine fever virus (ASFV) remains enzootic in most countries of Sub-Saharan Africa, today representing a major threat for the development of their swine industry. The uncontrolled presence of ASFV has favored its periodic exportation to other countries, the last event being in Georgia in 2007. Since then, ASFV has spread toward neighboring countries, reaching the European Union's east border in 2014. The lack of available vaccines against ASFV makes its control difficult; so far, only live attenuated viruses have demonstrated solid protection against homologous experimental challenges, but they have failed at inducing solid cross-protective immunity against heterologous viruses. Here we describe a new LAV candidate with unique cross-protective abilities: BA71ΔCD2. Inoculation of BA71ΔCD2 protected pigs not only against experimental challenge with BA71, the virulent parental strain, but also against heterologous viruses, including Georgia 2007/1, the genotype II strain of ASFV currently circulating in Eastern Europe. PMID:28814514

An ontology for major histocompatibility restriction.

PubMed

Vita, Randi; Overton, James A; Seymour, Emily; Sidney, John; Kaufman, Jim; Tallmadge, Rebecca L; Ellis, Shirley; Hammond, John; Butcher, Geoff W; Sette, Alessandro; Peters, Bjoern

2016-01-01

MHC molecules are a highly diverse family of proteins that play a key role in cellular immune recognition. Over time, different techniques and terminologies have been developed to identify the specific type(s) of MHC molecule involved in a specific immune recognition context. No consistent nomenclature exists across different vertebrate species. To correctly represent MHC related data in The Immune Epitope Database (IEDB), we built upon a previously established MHC ontology and created an ontology to represent MHC molecules as they relate to immunological experiments. This ontology models MHC protein chains from 16 species, deals with different approaches used to identify MHC, such as direct sequencing verses serotyping, relates engineered MHC molecules to naturally occurring ones, connects genetic loci, alleles, protein chains and multi-chain proteins, and establishes evidence codes for MHC restriction. Where available, this work is based on existing ontologies from the OBO foundry. Overall, representing MHC molecules provides a challenging and practically important test case for ontology building, and could serve as an example of how to integrate other ontology building efforts into web resources.

Nutrition in Patients with Gastric Cancer: An Update.

PubMed

Rosania, Rosa; Chiapponi, Costanza; Malfertheiner, Peter; Venerito, Marino

2016-05-01

Nutritional management of patients with gastric cancer (GC) represents a challenge. This review provides an overview of the present evidence on nutritional support in patients with GC undergoing surgery as well as in those with advanced disease. For patients undergoing surgery, the preoperative nutritional condition directly affects postoperative prognosis, overall survival and disease-specific survival. Perioperative nutritional support enriched with immune-stimulating nutrients reduces overall complications and hospital stay but not mortality after major elective gastrointestinal surgery. Early enteral nutrition after surgery improves early and long-term postoperative nutritional status and reduces the length of hospitalization as well. Vitamin B12 and iron deficiency are common metabolic sequelae after gastrectomy and warrant appropriate replacement. In malnourished patients with advanced GC, short-term home complementary parenteral nutrition improves the quality of life, nutritional status and functional status. Total home parenteral nutrition represents the only modality of caloric intake for patients with advanced GC who are unable to take oral or enteral nutrition. Early evaluations of nutritional status and nutritional support represent key aspects in the management of GC patients with both operable and advanced disease.

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics.

PubMed

Liu, Jianfang; Lichtenberg, Tara; Hoadley, Katherine A; Poisson, Laila M; Lazar, Alexander J; Cherniack, Andrew D; Kovatich, Albert J; Benz, Christopher C; Levine, Douglas A; Lee, Adrian V; Omberg, Larsson; Wolf, Denise M; Shriver, Craig D; Thorsson, Vesteinn; Hu, Hai

2018-04-05

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Copyright © 2018 Elsevier Inc. All rights reserved.

An OMIC biomarker detection algorithm TriVote and its application in methylomic biomarker detection.

PubMed

Xu, Cheng; Liu, Jiamei; Yang, Weifeng; Shu, Yayun; Wei, Zhipeng; Zheng, Weiwei; Feng, Xin; Zhou, Fengfeng

2018-04-01

Transcriptomic and methylomic patterns represent two major OMIC data sources impacted by both inheritable genetic information and environmental factors, and have been widely used as disease diagnosis and prognosis biomarkers. Modern transcriptomic and methylomic profiling technologies detect the status of tens of thousands or even millions of probing residues in the human genome, and introduce a major computational challenge for the existing feature selection algorithms. This study proposes a three-step feature selection algorithm, TriVote, to detect a subset of transcriptomic or methylomic residues with highly accurate binary classification performance. TriVote outperforms both filter and wrapper feature selection algorithms with both higher classification accuracy and smaller feature number on 17 transcriptomes and two methylomes. Biological functions of the methylome biomarkers detected by TriVote were discussed for their disease associations. An easy-to-use Python package is also released to facilitate the further applications.

Glomerular Diseases: Emerging Tests and Therapies for IgA Nephropathy

PubMed Central

Kiryluk, Krzysztof; Appel, Gerald B.

2014-01-01

Summary The last decade has seen major progress in understanding the pathogenesis as well as the prognosis and treatment of patients with IgA nephropathy (IgAN). Although the diagnostic criterion of a kidney biopsy demonstrating dominant or codominant IgA deposition remains unchanged, much more is known about the genetic and environmental factors predisposing to disease development and progression. These advances have led to the identification of novel diagnostic and prognostic markers. Among the most promising clinically are genetic profiling, quantification of galactose-deficient IgA1 levels, and measurement of anti-IgA1 immunoglobulins. While targeted treatment for IgAN remains elusive, there is mounting evidence for therapeutic interventions that alter the disease course. The appropriate validation and integration of these discoveries into clinical care represent a major challenge, but one that holds tremendous promise for refining prognostication, guiding therapy, and improving the lives of patients with IgAN. PMID:24071652

Glomerular diseases: emerging tests and therapies for IgA nephropathy.

PubMed

Canetta, Pietro A; Kiryluk, Krzysztof; Appel, Gerald B

2014-03-01

The last decade has seen major progress in understanding the pathogenesis as well as the prognosis and treatment of patients with IgA nephropathy (IgAN). Although the diagnostic criterion of a kidney biopsy demonstrating dominant or codominant IgA deposition remains unchanged, much more is known about the genetic and environmental factors predisposing to disease development and progression. These advances have led to the identification of novel diagnostic and prognostic markers. Among the most promising clinically are genetic profiling, quantification of galactose-deficient IgA1 levels, and measurement of anti-IgA1 immunoglobulins. While targeted treatment for IgAN remains elusive, there is mounting evidence for therapeutic interventions that alter the disease course. The appropriate validation and integration of these discoveries into clinical care represent a major challenge, but one that holds tremendous promise for refining prognostication, guiding therapy, and improving the lives of patients with IgAN.

[Haiti, new immigrant community in Chile].

PubMed

Sánchez P, Katherin; Valderas J, Jaime; Messenger C, Karen; Sánchez G, Carolina; Barrera Q, Francisco

2018-04-01

Migration is a growing phenomenon in Latin America influenced by several factors such as economic stability, employment, social welfare, education and health system. Currently Chile has a positive migration flow rate. Particularly, a significant number of Haitian immigrants has been observed du ring the last years, especially after earthquake of 2010. These immigrants present a different cultural background expressed in relevant aspects of living including parenting and healthcare. Knowing the Haitian culture and its health situation is relevant for a better understanding of their health needs. Haitian people come to Chile looking for a cordial reception and willing to find a place with better perspectives of wellbeing in every sense. Immigration represents a major challenge for Chilean health system that must be embraced. Integration efforts in jobs, health, education system and community living should be enhanced to ensure a prosper settlement in our country. A new immigration law is crucial to solving major problems derived from current law created in 1975.

Fibromodulin deficiency reduces collagen structural network but not glycosaminoglycan content in a syngeneic model of colon carcinoma.

PubMed

Olsson, P Olof; Kalamajski, Sebastian; Maccarana, Marco; Oldberg, Åke; Rubin, Kristofer

2017-01-01

Tumor barrier function in carcinoma represents a major challenge to treatment and is therefore an attractive target for increasing drug delivery. Variables related to tumor barrier include aberrant blood vessels, high interstitial fluid pressure, and the composition and structure of the extracellular matrix. One of the proteins associated with dense extracellular matrices is fibromodulin, a collagen fibrillogenesis modulator expressed in tumor stroma but scarce in normal loose connective tissues. Here, we investigated the effects of fibromodulin on stroma ECM in a syngeneic murine colon carcinoma model. We show that fibromodulin deficiency decreased collagen fibril thickness but glycosaminoglycan content and composition were unchanged. Furthermore, vascular density, pericyte coverage and macrophage amount were unaffected. Fibromodulin can therefore be a unique effector of dense collagen matrix assembly in tumor stroma and, without affecting other major matrix components or the cellular composition, can function as a main agent in tumor barrier function.

Structures of membrane proteins

PubMed Central

Vinothkumar, Kutti R.; Henderson, Richard

2010-01-01

In reviewing the structures of membrane proteins determined up to the end of 2009, we present in words and pictures the most informative examples from each family. We group the structures together according to their function and architecture to provide an overview of the major principles and variations on the most common themes. The first structures, determined 20 years ago, were those of naturally abundant proteins with limited conformational variability, and each membrane protein structure determined was a major landmark. With the advent of complete genome sequences and efficient expression systems, there has been an explosion in the rate of membrane protein structure determination, with many classes represented. New structures are published every month and more than 150 unique membrane protein structures have been determined. This review analyses the reasons for this success, discusses the challenges that still lie ahead, and presents a concise summary of the key achievements with illustrated examples selected from each class. PMID:20667175

The Hallmarks of Aging

PubMed Central

López-Otín, Carlos; Blasco, Maria A.; Partridge, Linda; Serrano, Manuel; Kroemer, Guido

2013-01-01

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contribution to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging with minimal side-effects. PMID:23746838

Exploiting virus-like particles as innovative vaccines against emerging viral infections.

PubMed

Jeong, Hotcherl; Seong, Baik Lin

2017-03-01

Emerging viruses pose a major threat to humans and livestock with global public health and economic burdens. Vaccination remains an effective tool to reduce this threat, and yet, the conventional cell culture often fails to produce sufficient vaccine dose. As an alternative to cell-culture based vaccine, virus-like particles (VLPs) are considered as a highpriority vaccine strategy against emerging viruses. VLPs represent highly ordered repetitive structures via macromolecular assemblies of viral proteins. The particulate nature allows efficient uptake into antigen presenting cells stimulating both innate and adaptive immune responses towards enhanced vaccine efficacy. Increasing research activity and translation opportunity necessitate the advances in the design of VLPs and new bioprocessing modalities for efficient and cost-effective production. Herein, we describe major achievements and challenges in this endeavor, with respect to designing strategies to harnessing the immunogenic potential, production platforms, downstream processes, and some exemplary cases in developing VLP-based vaccines.

From brain passage to cell adaptation: the road of human rabies vaccine development.

PubMed

Wu, Xianfu; Smith, Todd G; Rupprecht, Charles E

2011-11-01

A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines. Such candidates should be pure, potent, safe, effective and economical to produce, with broad cross-reactivity against viral variants of public health and veterinary importance. The history of licensed human vaccines reviewed herein demonstrates clearly how the field has evolved to the current state of more passive development and postexposure management. Modern cell culture techniques provide adequate viral substrates for production of representative verified virus seeds. In contrast to outdated nervous tissue-based rabies vaccines, once a suitable substrate is identified, production of high titer virus results in a major qualitative and quantitative difference. Given the current scenario of only inactivated vaccines for humans, highly cell-adapted and stable, attenuated rabies viruses are ideal candidates for consideration to meet the need for seed viruses in the future.

Corrosion detection and evolution monitoring in reinforced concrete structures by the use of fiber Bragg grating sensor

NASA Astrophysics Data System (ADS)

Ali-Alvarez, S.; Ferdinand, P.; Magne, S.; Nogueira, R. P.

2013-04-01

Corrosion of reinforced bar (rebar) in concrete structures represents a major issue in civil engineering works, being its detection and evolution a challenge for the applied research. In this work, we present a new methodology to corrosion detection in reinforced concrete structures, by combining Fiber Bragg Grating (FBG) sensors with the electrochemical and physical properties of rebar in a simplified assembly. Tests in electrolytic solutions and concrete were performed for pitting and general corrosion. The proposed Structural Health Monitoring (SHM) methodology constitutes a direct corrosion measurement potentially useful to implement or improve Condition-Based Maintenance (CBM) program for civil engineering concrete structures.

[Mineral and bone disorders in renal transplantation].

PubMed

Bacchetta, Justine; Lafage-Proust, Marie-Hélène; Chapurlat, Roland

2013-12-01

The deregulation of bone and mineral metabolism during chronic kidney disease (CKD) is a daily challenge for physicians, its management aiming at decreasing the risk of both fractures and vascular calcifications. Renal transplantation in the context of CKD, with pre-existing renal osteodystrophy as well as nutritional impairment, chronic inflammation, hypogonadism and corticosteroids exposure, represents a major risk factor for bone impairment in the post-transplant period. The aim of this review is therefore to provide an update on the pathophysiology of mineral and bone disorders after renal transplantation. Copyright © 2013 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Genetic heterogeneity in autism: From single gene to a pathway perspective.

PubMed

An, Joon Yong; Claudianos, Charles

2016-09-01

The extreme genetic heterogeneity of autism spectrum disorder (ASD) represents a major challenge. Recent advances in genetic screening and systems biology approaches have extended our knowledge of the genetic etiology of ASD. In this review, we discuss the paradigm shift from a single gene causation model to pathway perturbation model as a guide to better understand the pathophysiology of ASD. We discuss recent genetic findings obtained through next-generation sequencing (NGS) and examine various integrative analyses using systems biology and complex networks approaches that identify convergent patterns of genetic elements associated with ASD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retention of the Native Epigenome in Purified Mammalian Chromatin

PubMed Central

Ehrensberger, Andreas H.; Franchini, Don-Marc; East, Philip; George, Roger; Matthews, Nik; Maslen, Sarah L.; Svejstrup, Jesper Q.

2015-01-01

A protocol is presented for the isolation of native mammalian chromatin as fibers of 25–250 nucleosomes under conditions that preserve the natural epigenetic signature. The material is composed almost exclusively of histones and DNA and conforms to the structure expected by electron microscopy. All sequences probed for were retained, indicating that the material is representative of the majority of the genome. DNA methylation marks and histone marks resembled the patterns observed in vivo. Importantly, nucleosome positions also remained largely unchanged, except on CpG islands, where nucleosomes were found to be unstable. The technical challenges of reconstituting biochemical reactions with native mammalian chromatin are discussed. PMID:26248330

Biological Tools to Study the Effects of Environmental Contaminants at the Feto–Maternal Interface

PubMed Central

Mannelli, Chiara; Ietta, Francesca; Avanzati, Anna Maria; Skarzynski, Dariusz

2015-01-01

The identification of reproductive toxicants is a major scientific challenge for human health. Prenatal life is the most vulnerable and important time span of human development. For obvious ethical reasons, in vivo models cannot be used in human pregnancy, and animal models do not perfectly reflect human physiology. This review describes the in vitro test models representative of the human feto–maternal interface and the effects of environmental chemicals with estrogen-like activity, mainly bisphenol A and para-nonylphenol, with a particular emphasis on the effects at low, nontoxic doses similar to concentrations commonly detected in the population. PMID:26740808

Introduction: The State of Obesity in 2017.

PubMed

Kushner, Robert F; Kahan, Scott

2018-01-01

Obesity continues to be a major national and global health challenge and a risk factor for an expanding set of chronic diseases. In 2015, high body mass index contributed to 4.0 million deaths globally, which represented 7.1% of the deaths from any cause. Obesity is now regarded as a disease, and multiple health care societies have begun to tackle obesity as a discrete target for assessment and treatment that is supported by several position statements and guidelines. Nonetheless, a perception and treatment gap continues to exist between health care providers and patients regarding the provision of obesity care. Copyright © 2017 Elsevier Inc. All rights reserved.

Identifying molecular drivers of gastric cancer through next-generation sequencing.

PubMed

Liang, Han; Kim, Yon Hui

2013-11-01

Gastric cancer is the second most common cause of cancer-related death in the world, representing a major global health issue. The high mortality rate is largely due to the lack of effective medical treatment for advanced stages of this disease. Recently next-generation sequencing (NGS) technology has become a revolutionary tool for cancer research, and several NGS studies in gastric cancer have been published. Here we review the insights gained from these studies regarding how use NGS to elucidate the molecular basis of gastric cancer and identify potential therapeutic targets. We also discuss the challenges and future directions of such efforts. Published by Elsevier Ireland Ltd.

Sediment dynamics of muddy coasts and estuaries in China: An introduction

NASA Astrophysics Data System (ADS)

Wang, Xiao Hua; Gan, Jianping; Lowe, Ryan

2018-06-01

Sustainable livelihoods and economic development is supported by effective management of coastal and estuarine assets, which represents a huge and, in many instances, extremely costly challenge, in particular given the multiple stakeholders with mixed interests in ports and harbours and the adjacent coastal and marine environments. Given the importance of the well-being of coastal environments, the rapid expansion of major ports has caused concerns within both the scientific community and the general public about the possible environmental consequences. The implications of these rapid coastal changes, including urbanization and industrialization, are often highly degraded natural systems, ecosystems with compromised functions, and intense conflict and competition between users.

The Candida albicans Biofilm Matrix: Composition, Structure and Function.

PubMed

Pierce, Christopher G; Vila, Taissa; Romo, Jesus A; Montelongo-Jauregui, Daniel; Wall, Gina; Ramasubramanian, Anand; Lopez-Ribot, Jose L

2017-03-01

A majority of infections caused by Candida albicans -the most frequent fungal pathogen-are associated with biofilm formation. A salient feature of C. albicans biofilms is the presence of the biofilm matrix. This matrix is composed of exopolymeric materials secreted by sessile cells within the biofilm, in which all classes of macromolecules are represented, and provides protection against environmental challenges. In this review, we summarize the knowledge accumulated during the last two decades on the composition, structure, and function of the C. albicans biofilm matrix. Knowledge of the matrix components, its structure, and function will help pave the way to novel strategies to combat C. albicans biofilm infections.

The Candida albicans Biofilm Matrix: Composition, Structure and Function

PubMed Central

Pierce, Christopher G.; Vila, Taissa; Romo, Jesus A.; Montelongo-Jauregui, Daniel; Wall, Gina; Ramasubramanian, Anand; Lopez-Ribot, Jose L.

2017-01-01

A majority of infections caused by Candida albicans—the most frequent fungal pathogen—are associated with biofilm formation. A salient feature of C. albicans biofilms is the presence of the biofilm matrix. This matrix is composed of exopolymeric materials secreted by sessile cells within the biofilm, in which all classes of macromolecules are represented, and provides protection against environmental challenges. In this review, we summarize the knowledge accumulated during the last two decades on the composition, structure, and function of the C. albicans biofilm matrix. Knowledge of the matrix components, its structure, and function will help pave the way to novel strategies to combat C. albicans biofilm infections. PMID:28516088

Metallic Biomaterials: Current Challenges and Opportunities

PubMed Central

Prasad, Karthika; Bazaka, Olha; Chua, Ming; Rochford, Madison; Fedrick, Liam; Spoor, Jordan; Symes, Richard; Tieppo, Marcus; Collins, Cameron; Cao, Alex; Ostrikov, Kostya (Ken); Bazaka, Kateryna

2017-01-01

Metallic biomaterials are engineered systems designed to provide internal support to biological tissues and they are being used largely in joint replacements, dental implants, orthopaedic fixations and stents. Higher biomaterial usage is associated with an increased incidence of implant-related complications due to poor implant integration, inflammation, mechanical instability, necrosis and infections, and associated prolonged patient care, pain and loss of function. In this review, we will briefly explore major representatives of metallic biomaterials along with the key existing and emerging strategies for surface and bulk modification used to improve biointegration, mechanical strength and flexibility of biometals, and discuss their compatibility with the concept of 3D printing. PMID:28773240

Cattle Uterus: A Novel Animal Laboratory Model for Advanced Hysteroscopic Surgery Training

PubMed Central

Ewies, Ayman A. A.; Khan, Zahid R.

2015-01-01

In recent years, due to reduced training opportunities, the major shift in surgical training is towards the use of simulation and animal laboratories. Despite the merits of Virtual Reality Simulators, they are far from representing the real challenges encountered in theatres. We introduce the “Cattle Uterus Model” in the hope that it will be adopted in training courses as a low cost and easy-to-set-up tool. It adds new dimensions to the advanced hysteroscopic surgery training experience by providing tactile sensation and simulating intraoperative difficulties. It complements conventional surgical training, aiming to maximise clinical exposure and minimise patients' harm. PMID:26265918

Virtual Inertia: Current Trends and Future Directions

DOE PAGES

Tamrakar, Ujjwol; Shrestha, Dipesh; Maharjan, Manisha; ...

2017-06-26

The modern power system is progressing from a synchronous machine-based system towards an inverter-dominated system, with a large-scale penetration of renewable energy sources (RESs) like wind and photovoltaics. RES units today represent a major share of the generation, and the traditional approach of integrating themas grid following units can lead to frequency instability. Many researchers have pointed towards using inverters with virtual inertia control algorithms so that they appear as synchronous generators to the grid, maintaining and enhancing system stability. Our paper presents a literature review of the current state-of-the-art of virtual inertia implementation techniques, and explores potential research directionsmore » and challenges. The major virtual inertia topologies are compared and classified. Through literature review and simulations of some selected topologies it has been shown that similar inertial response can be achieved by relating the parameters of these topologies through time constants and inertia constants, although the exact frequency dynamics may vary slightly. The suitability of a topology depends on system control architecture and desired level of detail in replication of the dynamics of synchronous generators. We present a discussion on the challenges and research directions which points out several research needs, especially for systems level integration of virtual inertia systems.« less

Virtual Inertia: Current Trends and Future Directions

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

Tamrakar, Ujjwol; Shrestha, Dipesh; Maharjan, Manisha

The modern power system is progressing from a synchronous machine-based system towards an inverter-dominated system, with a large-scale penetration of renewable energy sources (RESs) like wind and photovoltaics. RES units today represent a major share of the generation, and the traditional approach of integrating themas grid following units can lead to frequency instability. Many researchers have pointed towards using inverters with virtual inertia control algorithms so that they appear as synchronous generators to the grid, maintaining and enhancing system stability. Our paper presents a literature review of the current state-of-the-art of virtual inertia implementation techniques, and explores potential research directionsmore » and challenges. The major virtual inertia topologies are compared and classified. Through literature review and simulations of some selected topologies it has been shown that similar inertial response can be achieved by relating the parameters of these topologies through time constants and inertia constants, although the exact frequency dynamics may vary slightly. The suitability of a topology depends on system control architecture and desired level of detail in replication of the dynamics of synchronous generators. We present a discussion on the challenges and research directions which points out several research needs, especially for systems level integration of virtual inertia systems.« less

A mathematical analysis of adaptations to the metabolic fate of fructose in essential fructosuria subjects.

PubMed

Allen, R J; Musante, Cynthia J

2018-04-17

Fructose is a major component of Western diets and is implicated in the pathogenesis of obesity and type 2 diabetes. In response to an oral challenge, the majority of fructose is cleared during "first-pass" liver metabolism, primarily via phosphorylation by ketohexokinase (KHK). A rare benign genetic deficiency in KHK, called essential fructosuria (EF), leads to altered fructose metabolism. The only reported symptom of EF is the appearance of fructose in the urine following either oral or intravenous fructose administration. Here we develop and use a mathematical model to investigate the adaptations to altered fructose metabolism in people with EF. Firstly, the model is calibrated to fit available data in normal healthy subjects. Then, to mathematically represent EF subjects we systematically implement metabolic adaptations such that model simulations match available data for this phenotype. We hypothesize that these modifications represent the major metabolic adaptations present in these subjects. This modeling approach suggests that several other aspects of fructose metabolism, beyond hepatic KHK deficiency, are altered and contribute to the etiology of this benign condition. Specifically, we predict that fructose absorption into the portal vein is altered, peripheral metabolism is slowed, renal re-absorption of fructose is mostly ablated and that alternate pathways for hepatic metabolism of fructose are up-regulated. Moreover, these findings have implications for drug discovery and development, suggesting that the therapeutic targeting of fructose metabolism could lead to unexpected metabolic adaptations, potentially due to a physiological response to high fructose conditions.

Challenges Facing Early Childhood Programs Worldwide

ERIC Educational Resources Information Center

Neugebauer, Roger

2008-01-01

In this article, the author presents the challenges faced by early childhood education in 29 countries, according to the World Forum National Representatives and Global Leaders for Young Children. The countries represented in these responses include: Azerbaijan, Bangladesh, Bolivia, Brazil, Canada, Denmark, Egypt, Fiji, India, Iran, Iraq, Japan,…

Egg donation, surrogate mothering, and cloning: attitudes of men and women in Germany based on a representative survey.

PubMed

Stöbel-Richter, Yve; Goldschmidt, Susanne; Brähler, Elmar; Weidner, Kerstin; Beutel, Manfred

2009-07-01

To determine opinions and attitudes of the German general population toward the treatment methods of reproductive medicine: egg donation, surrogate mothering, and reproductive cloning. Representative survey. German general population: face-to-face interviews at home with 2,110 persons, aged 18-50 years. Patients were not included. No interventions took place. Approval and disapproval of treatment methods of reproductive medicine and preimplantation genetic diagnosis were assessed by questionnaires regarding medical, age, reasons, or general. Overall, the diverse treatment methods of reproductive medicine found comparable rates of approval and disapproval. Legalization of egg donation was approved by a slight majority (50.8%), particularly for medical reasons (35.9%). Surrogate mothering found lower overall rates of approval (43.7%), 28.5% supported an admission for medical reasons. Reproductive cloning was rejected by the vast majority (82.9%). Attitudes to reproductive medicine were affected by age and the individual reproductive experiences. New techniques in reproductive medicine and their development provide hope and health promises for affected couples but also entail long-term risks and ethical issues. Balancing the individual's right to a reproductive autonomy and choice and ethical standards will constitute a future challenge for society. Results demonstrate considerable uncertainty and information deficits in the community.

Isoelectric point-based fractionation by HiRIEF coupled to LC-MS allows for in-depth quantitative analysis of the phosphoproteome.

PubMed

Panizza, Elena; Branca, Rui M M; Oliviusson, Peter; Orre, Lukas M; Lehtiö, Janne

2017-07-03

Protein phosphorylation is involved in the regulation of most eukaryotic cells functions and mass spectrometry-based analysis has made major contributions to our understanding of this regulation. However, low abundance of phosphorylated species presents a major challenge in achieving comprehensive phosphoproteome coverage and robust quantification. In this study, we developed a workflow employing titanium dioxide phospho-enrichment coupled with isobaric labeling by Tandem Mass Tags (TMT) and high-resolution isoelectric focusing (HiRIEF) fractionation to perform in-depth quantitative phosphoproteomics starting with a low sample quantity. To benchmark the workflow, we analyzed HeLa cells upon pervanadate treatment or cell cycle arrest in mitosis. Analyzing 300 µg of peptides per sample, we identified 22,712 phosphorylation sites, of which 19,075 were localized with high confidence and 1,203 are phosphorylated tyrosine residues, representing 6.3% of all detected phospho-sites. HiRIEF fractions with the most acidic isoelectric points are enriched in multiply phosphorylated peptides, which represent 18% of all the phospho-peptides detected in the pH range 2.5-3.7. Cross-referencing with the PhosphoSitePlus database reveals 1,264 phosphorylation sites that have not been previously reported and kinase association analysis suggests that a subset of these may be functional during the mitotic phase.

Pediatric Old World cutaneous leishmaniasis treated with oral fluconazole: A case series.

PubMed

Michelerio, Andrea; Barruscotti, Stefania; Bossi, Grazia; Brazzelli, Valeria

2018-05-01

Cutaneous leishmaniasis has an incidence of 0.7-1.2 million cases per year and represents a growing concern in the outpatient dermatologic practice in Europe because of imported cases due to increased travel to risk areas and to immigration phenomena. When dealing with children, the treatment can be challenging because of side effects and pain of classic antimonial therapy leading to poor rates of course completion and requirement of sedation for several children. We retrospectively studied three cases of cutaneous leishmaniasis in pediatric patients, between the ages of 3 and 6 years of age, treated with oral fluconazole. We examined the efficacy, the tolerability, the safety profile and the cosmetic result of fluconazole at a dose of 6 mg/kg/daily for 6 weeks. The patients had a complete resolution of their lesions with minimal scarring. No adverse effect was reported. The leishmaniasis species identified were L. major or L. tropica. Considering sides effects and the parents' and the clinician's concern for systemic treatment in the pediatric population, fluconazole represents a valid, safe and easily manageable option for Old World cutaneous leishmaniasis in pediatric outpatients caused by L. major or L. tropica. © 2018 Wiley Periodicals, Inc.

Formicine ants: An arthropod source for the pumiliotoxin alkaloids of dendrobatid poison frogs

PubMed Central

Saporito, Ralph A.; Garraffo, H. Martin; Donnelly, Maureen A.; Edwards, Adam L.; Longino, John T.; Daly, John W.

2004-01-01

A remarkable diversity of bioactive lipophilic alkaloids is present in the skin of poison frogs and toads worldwide. Originally discovered in neotropical dendrobatid frogs, these alkaloids are now known from mantellid frogs of Madagascar, certain myobatrachid frogs of Australia, and certain bufonid toads of South America. Presumably serving as a passive chemical defense, these alkaloids appear to be sequestered from a variety of alkaloid-containing arthropods. The pumiliotoxins represent a major, widespread, group of alkaloids that are found in virtually all anurans that are chemically defended by the presence of lipophilic alkaloids. Identifying an arthropod source for these alkaloids has been a considerable challenge for chemical ecologists. However, an extensive collection of neotropical forest arthropods has now revealed a putative arthropod source of the pumiliotoxins. Here we report on the presence of pumiliotoxins in formicine ants of the genera Brachymyrmex and Paratrechina, as well as the presence of these ants in the stomach contents of the microsympatric pumiliotoxin-containing dendrobatid frog, Dendrobates pumilio. These pumiliotoxins are major alkaloids in D. pumilio, and Brachymyrmex and Paratrechina ants now represent the only known dietary sources of these toxic alkaloids. These findings further support the significance of ant-specialization and alkaloid sequestration in the evolution of bright warning coloration in poison frogs and toads. PMID:15128938

The Public Health Challenge.

ERIC Educational Resources Information Center

Ember, Lois R.

1987-01-01

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

Anaesthetic perioperative management of patients with pancreatic cancer

PubMed Central

De Pietri, Lesley; Montalti, Roberto; Begliomini, Bruno

2014-01-01

Pancreatic cancer remains a significant and unresolved therapeutic challenge. Currently, the only curative treatment for pancreatic cancer is surgical resection. Pancreatic surgery represents a technically demanding major abdominal procedure that can occasionally lead to a number of pathophysiological alterations resulting in increased morbidity and mortality. Systemic, rather than surgical complications, cause the majority of deaths. Because patients are increasingly referred to surgery with at advanced ages and because pancreatic surgery is extremely complex, anaesthesiologists and surgeons play a crucial role in preoperative evaluations and diagnoses for surgical intervention. The anaesthetist plays a key role in perioperative management and can significantly influence patient outcome. To optimise overall care, patients should be appropriately referred to tertiary centres, where multidisciplinary teams (surgical, medical, radiation oncologists, gastroenterologists, interventional radiologists and anaesthetists) work together and where close cooperation between surgeons and anaesthesiologists promotes the safe performance of major gastrointestinal surgeries with acceptable morbidity and mortality rates. In this review, we sought to provide simple daily recommendations to the clinicians who manage pancreatic surgery patients to make their work easier and suggest a joint approach between surgeons and anaesthesiologists in daily decision making. PMID:24605028

Trends in genome dynamics among major orders of insects revealed through variations in protein families.

PubMed

Rappoport, Nadav; Linial, Michal

2015-08-07

Insects belong to a class that accounts for the majority of animals on earth. With over one million identified species, insects display a huge diversity and occupy extreme environments. At present, there are dozens of fully sequenced insect genomes that cover a range of habitats, social behavior and morphologies. In view of such diverse collection of genomes, revealing evolutionary trends and charting functional relationships of proteins remain challenging. We analyzed the relatedness of 17 complete proteomes representative of proteomes from insects including louse, bee, beetle, ants, flies and mosquitoes, as well as an out-group from the crustaceans. The analyzed proteomes mostly represented the orders of Hymenoptera and Diptera. The 287,405 protein sequences from the 18 proteomes were automatically clustered into 20,933 families, including 799 singletons. A comprehensive analysis based on statistical considerations identified the families that were significantly expanded or reduced in any of the studied organisms. Among all the tested species, ants are characterized by an exceptionally high rate of family gain and loss. By assigning annotations to hundreds of species-specific families, the functional diversity among species and between the major clades (Diptera and Hymenoptera) is revealed. We found that many species-specific families are associated with receptor signaling, stress-related functions and proteases. The highest variability among insects associates with the function of transposition and nucleic acids processes (collectively coined TNAP). Specifically, the wasp and ants have an order of magnitude more TNAP families and proteins relative to species that belong to Diptera (mosquitoes and flies). An unsupervised clustering methodology combined with a comparative functional analysis unveiled proteomic signatures in the major clades of winged insects. We propose that the expansion of TNAP families in Hymenoptera potentially contributes to the accelerated genome dynamics that characterize the wasp and ants.

Modeling dynamics of large tabular icebergs submerged in the ocean

NASA Astrophysics Data System (ADS)

Adcroft, A.; Stern, A. A.; Sergienko, O. V.

2017-12-01

Large tabular icebergs account for a major fraction of the ice calved from the Antarctic ice shelves, and have long lifetimes due to their size. They drift for long distances, interacting with the local ocean circulation, impacting bottom-water formation, sea-ice formation, and biological productivity in the vicinity of the icebergs. However, due to their large horizontal extent and mass, it is challenging to consistently represent large tabular icebergs in global ocean circulation models and so large tabular icebergs are not currently represented in climate models. In this study we develop a novel framework to model large tabular icebergs submerged in the ocean. In this framework, a tabular iceberg is represented by a collection of Lagrangian elements that are linked through rigid bonds. The Lagrangian elements are finite-area modifications of the point-particles used in previous studies to represent small icebergs. These elements interact with the ocean by exerting pressure on the ocean surface, and through melt water and momentum exchange. A breaking of the rigid bonds allows the model to emulate calving events (i.e. detachment of a tabular iceberg from an ice shelf), and to emulate the breaking up of tabular icebergs into smaller pieces. Idealized simulations of the calving of a tabular iceberg, subsequent drift and breakup, demonstrate the capabilities of the new framework with a promise that climate models may soon be able to represent large tabular icebergs.

Simulating the impacts of disturbances on forest carbon cycling in North America: Processes, data, models, and challenges

USGS Publications Warehouse

Liu, Shuguang; Bond-Lamberty, Ben; Hicke, Jeffrey A.; Vargas, Rodrigo; Zhao, Shuqing; Chen, Jing; Edburg, Steven L.; Hu, Yueming; Liu, Jinxun; McGuire, A. David; Xiao, Jingfeng; Keane, Robert; Yuan, Wenping; Tang, Jianwu; Luo, Yiqi; Potter, Christopher; Oeding, Jennifer

2011-01-01

Forest disturbances greatly alter the carbon cycle at various spatial and temporal scales. It is critical to understand disturbance regimes and their impacts to better quantify regional and global carbon dynamics. This review of the status and major challenges in representing the impacts of disturbances in modeling the carbon dynamics across North America revealed some major advances and challenges. First, significant advances have been made in representation, scaling, and characterization of disturbances that should be included in regional modeling efforts. Second, there is a need to develop effective and comprehensive process‐based procedures and algorithms to quantify the immediate and long‐term impacts of disturbances on ecosystem succession, soils, microclimate, and cycles of carbon, water, and nutrients. Third, our capability to simulate the occurrences and severity of disturbances is very limited. Fourth, scaling issues have rarely been addressed in continental scale model applications. It is not fully understood which finer scale processes and properties need to be scaled to coarser spatial and temporal scales. Fifth, there are inadequate databases on disturbances at the continental scale to support the quantification of their effects on the carbon balance in North America. Finally, procedures are needed to quantify the uncertainty of model inputs, model parameters, and model structures, and thus to estimate their impacts on overall model uncertainty. Working together, the scientific community interested in disturbance and its impacts can identify the most uncertain issues surrounding the role of disturbance in the North American carbon budget and develop working hypotheses to reduce the uncertainty

Urban runoff (URO) process for MODFLOW 2005: simulation of sub-grid scale urban hydrologic processes in Broward County, FL

USGS Publications Warehouse

Decker, Jeremy D.; Hughes, J.D.

2013-01-01

Climate change and sea-level rise could cause substantial changes in urban runoff and flooding in low-lying coast landscapes. A major challenge for local government officials and decision makers is to translate the potential global effects of climate change into actionable and cost-effective adaptation and mitigation strategies at county and municipal scales. A MODFLOW process is used to represent sub-grid scale hydrology in urban settings to help address these issues. Coupled interception, surface water, depression, and unsaturated zone storage are represented. A two-dimensional diffusive wave approximation is used to represent overland flow. Three different options for representing infiltration and recharge are presented. Additional features include structure, barrier, and culvert flow between adjacent cells, specified stage boundaries, critical flow boundaries, source/sink surface-water terms, and the bi-directional runoff to MODFLOW Surface-Water Routing process. Some abilities of the Urban RunOff (URO) process are demonstrated with a synthetic problem using four land uses and varying cell coverages. Precipitation from a hypothetical storm was applied and cell by cell surface-water depth, groundwater level, infiltration rate, and groundwater recharge rate are shown. Results indicate the URO process has the ability to produce time-varying, water-content dependent infiltration and leakage, and successfully interacts with MODFLOW.

Telling plant species apart with DNA: from barcodes to genomes

PubMed Central

Li, De-Zhu; van der Bank, Michelle

2016-01-01

Land plants underpin a multitude of ecosystem functions, support human livelihoods and represent a critically important component of terrestrial biodiversity—yet many tens of thousands of species await discovery, and plant identification remains a substantial challenge, especially where material is juvenile, fragmented or processed. In this opinion article, we tackle two main topics. Firstly, we provide a short summary of the strengths and limitations of plant DNA barcoding for addressing these issues. Secondly, we discuss options for enhancing current plant barcodes, focusing on increasing discriminatory power via either gene capture of nuclear markers or genome skimming. The former has the advantage of establishing a defined set of target loci maximizing efficiency of sequencing effort, data storage and analysis. The challenge is developing a probe set for large numbers of nuclear markers that works over sufficient phylogenetic breadth. Genome skimming has the advantage of using existing protocols and being backward compatible with existing barcodes; and the depth of sequence coverage can be increased as sequencing costs fall. Its non-targeted nature does, however, present a major informatics challenge for upscaling to large sample sets. This article is part of the themed issue ‘From DNA barcodes to biomes’. PMID:27481790

Developmental origins of health and disease--global public health implications.

PubMed

Hanson, M A; Gluckman, P D

2015-01-01

The rapidly rising prevalence of non-communicable diseases (NCDs) represents a major challenge to public health and clinical medicine globally. NCDs are increasing rapidly in high-income countries, but even more rapidly in some low-middle-income countries with insufficient resources to meet the challenge. Whilst not identified in the Millennium Development Goals, there is much attention paid to NCDs in the discussions at many levels on the Sustainable Development Goals, as they underpin economic, social and environmental development in the post-2015 era. In this article, we discuss how a life-course approach to health, commencing of necessity in early development, can provide new opportunities for addressing this challenge. The approach can leverage human health capital throughout life and across generations. New insights into mechanisms, especially those processes by which the developmental environment affects epigenetic processes in the developing offspring, offer the prospect of identifying biomarkers of future risks. New interventions to promote health literacy, lifestyle and physical fitness in adolescents, young adults and their children hold great promise. In this respect, health-care professionals concerned with preconceptional, pregnancy and newborn care will have a vital role to play. Copyright © 2014 Elsevier Ltd. All rights reserved.

Challenges of standardized continuous quality improvement programs in community pharmacies: the case of SafetyNET-Rx.

PubMed

Boyle, Todd A; MacKinnon, Neil J; Mahaffey, Thomas; Duggan, Kellie; Dow, Natalie

2012-01-01

Research on continuous quality improvement (CQI) in community pharmacies lags in comparison to service, manufacturing, and various health care sectors. As a result, very little is known about the challenges community pharmacies face when implementing CQI programs in general, let alone the challenges of implementing a standardized and technologically sophisticated one. This research identifies the initial challenges of implementing a standardized CQI program in community pharmacies and how such challenges were addressed by pharmacy staff. Through qualitative interviews, a multisite study of the SafetyNET-Rx CQI program involving community pharmacies in Nova Scotia, Canada, was performed to identify such challenges. Interviews were conducted with the CQI facilitator (ie, staff pharmacist or technician) in 55 community pharmacies that adopted the SafetyNET-Rx program. Of these 55 pharmacies, 25 were part of large national corporate chains, 22 were part of banner chains, and 8 were independent pharmacies. A total of 10 different corporate chains and banners were represented among the 55 pharmacies. Thematic content analysis using well-established coding procedures was used to explore the interview data and elicit the key challenges faced. Six major challenges were identified, specifically finding time to report, having all pharmacy staff involved in quality-related event (QRE) reporting, reporting apprehensiveness, changing staff relationships, meeting to discuss QREs, and accepting the online technology. Challenges were addressed in a number of ways including developing a manual-online hybrid reporting system, managers paying staff to meet after hours, and pharmacy managers showing visible commitment to QRE reporting and learning. This research identifies key challenges to implementing CQI programs in community pharmacies and also provides a starting point for future research relating to how the challenges of QRE reporting and learning in community pharmacies change over time. Copyright © 2012 Elsevier Inc. All rights reserved.

From Amazonia to the Atlantic forest: molecular phylogeny of Phyzelaphryninae frogs reveals unexpected diversity and a striking biogeographic pattern emphasizing conservation challenges.

PubMed

Fouquet, Antoine; Loebmann, Daniel; Castroviejo-Fisher, Santiago; Padial, José M; Orrico, Victor G D; Lyra, Mariana L; Roberto, Igor Joventino; Kok, Philippe J R; Haddad, Célio F B; Rodrigues, Miguel T

2012-11-01

Documenting the Neotropical amphibian diversity has become a major challenge facing the threat of global climate change and the pace of environmental alteration. Recent molecular phylogenetic studies have revealed that the actual number of species in South American tropical forests is largely underestimated, but also that many lineages are millions of years old. The genera Phyzelaphryne (1 sp.) and Adelophryne (6 spp.), which compose the subfamily Phyzelaphryninae, include poorly documented, secretive, and minute frogs with an unusual distribution pattern that encompasses the biotic disjunction between Amazonia and the Atlantic forest. We generated >5.8 kb sequence data from six markers for all seven nominal species of the subfamily as well as for newly discovered populations in order to (1) test the monophyly of Phyzelaphryninae, Adelophryne and Phyzelaphryne, (2) estimate species diversity within the subfamily, and (3) investigate their historical biogeography and diversification. Phylogenetic reconstruction confirmed the monophyly of each group and revealed deep subdivisions within Adelophryne and Phyzelaphryne, with three major clades in Adelophryne located in northern Amazonia, northern Atlantic forest and southern Atlantic forest. Our results suggest that the actual number of species in Phyzelaphryninae is, at least, twice the currently recognized species diversity, with almost every geographically isolated population representing an anciently divergent candidate species. Such results highlight the challenges for conservation, especially in the northern Atlantic forest where it is still degraded at a fast pace. Molecular dating revealed that Phyzelaphryninae originated in Amazonia and dispersed during early Miocene to the Atlantic forest. The two Atlantic forest clades of Adelophryne started to diversify some 7 Ma minimum, while the northern Amazonian Adelophryne diversified much earlier, some 13 Ma minimum. This striking biogeographic pattern coincides with major events that have shaped the face of the South American continent, as we know it today. Copyright © 2012 Elsevier Inc. All rights reserved.

Facilitators, challenges, and collaborative activities in faith and health partnerships to address health disparities.

PubMed

Kegler, Michelle C; Hall, Sarah M; Kiser, Mimi

2010-10-01

Interest in partnering with faith-based organizations (FBOs) to address health disparities has grown in recent years. Yet relatively little is known about these types of partnerships. As part of an evaluation of the Institute for Faith and Public Health Collaborations, representatives of 34 faith-health teams (n = 61) completed semi-structured interviews. Interviews were tape recorded, transcribed, and coded by two members of the evaluation team to identify themes. Major facilitators to faith-health collaborative work were passion and commitment, importance of FBOs in communities, favorable political climate, support from community and faith leaders, diversity of teams, and mutual trust and respect. Barriers unique to faith and health collaboration included discomfort with FBOs, distrust of either health agencies or FBOs, diversity within faith communities, different agendas, separation of church and state, and the lack of a common language. Findings suggest that faith-health partnerships face unique challenges but are capable of aligning resources to address health disparities.

The Future of Gero-Oncology Nursing.

PubMed

Kagan, Sarah H

2016-02-01

To project the future of gero-oncology nursing as a distinct specialty, framed between analysis of current challenges and explication of prospective solutions. Peer-reviewed literature, policy directives, web-based resources, and author expertise. Oncology nursing faces several challenges in meeting the needs of older people living with cancer. Realigning cancer nursing education, practice, and research to match demographic and epidemiological realities mandates redesign. Viewing geriatric oncology as an optional sub-specialty limits oncology nursing, where older people represent the majority of oncology patients and cancer survivors. The future of gero-oncology nursing lies in transforming oncology nursing itself. Specific goals to achieve transformation of oncology nursing into gero-oncology nursing include assuring integrated foundational aging and cancer content across entry-level nursing curricula; assuring a gero-competent oncology nursing workforce with integrated continuing education; developing gero-oncology nurse specialists in advanced practice roles; and cultivating nurse leadership in geriatric oncology program development and administration along with expanding the scope and sophistication of gero-oncology nursing science. Copyright © 2015 Elsevier Inc. All rights reserved.

Extending Synthetic Routes for Oligosaccharides by Enzyme, Substrate and Reaction Engineering

NASA Astrophysics Data System (ADS)

Seibel, Jürgen; Jördening, Hans-Joachim; Buchholz, Klaus

The integration of all relevant tools for bioreaction engineering has been a recent challenge. This approach should notably favor the production of oligo- and polysaccharides, which is highly complex due to the requirements of regio- and stereoselectivity. Oligosaccharides (OS) and polysaccharides (PS) have found many interests in the fields of food, pharmaceuticals, and cosmetics due to different specific properties. Food, sweeteners, and food ingredients represent important sectors where OS are used in major amounts. Increasing attention has been devoted to the sophisticated roles of OS and glycosylated compounds, at cell or membrane surfaces, and their function, e.g., in infection and cancer proliferation. The challenge for synthesis is obvious, and convenient approaches using cheap and readily available substrates and enzymes will be discussed. We report on new routes for the synthesis of oligosaccharides (OS), with emphasis on enzymatic reactions, since they offer unique properties, proceeding highly regio- and stereoselective in water solution, and providing for high yields in general.

Sustainability and in situ monitoring in battery development

NASA Astrophysics Data System (ADS)

Grey, C. P.; Tarascon, J. M.

2017-01-01

The development of improved rechargeable batteries represents a major technological challenge for this new century, as batteries constitute the limiting components in the shift from petrol (gasoline) powered to electric vehicles, while also enabling the use of more renewable energy on the grid. To minimize the ecological implications associated with their wider use, we must integrate sustainability of battery materials into our research endeavours, choosing chemistries that have a minimum footprint in nature and that are more readily recycled or integrated into a full circular economy. Sustainability and cost concerns require that we greatly increase the battery lifetime and consider second lives for batteries. As part of this, we must monitor the state of health of batteries continuously during operation to minimize their degradation. It is thus important to push the frontiers of operando techniques to monitor increasingly complex processes. In this Review, we will describe key advances in both more sustainable chemistries and operando techniques, along with some of the remaining challenges and possible solutions, as we personally perceive them.

Using intersectionality responsibly: Toward critical epistemology, structural analysis, and social justice activism.

PubMed

Moradi, Bonnie; Grzanka, Patrick R

2017-10-01

The increasing popularity of the concept of intersectionality in the social sciences, including in psychology, represents an opportunity to reflect on the state of stewardship of this concept, its roots, and its promise. In this context, the authors aim to promote responsible stewardship of intersectionality and to tip the momentum of intersectionality's flourishing toward fuller use and engagement of its roots and promise for understanding and challenging dynamics of power, privilege, and oppression. To this end, this article provides a set of guidelines for reflection and action. The authors organize these guidelines along 3 major formulations of intersectionality: intersectionality as a field of study, as analytic strategy or disposition, and as critical praxis for social justice. Ultimately, the authors call for expanding the use of intersectionality toward fuller engagement with its roots in Black feminist thought, its current interdisciplinary richness and potential, and its central aims to challenge and transform structures and systems of power, privilege, and oppression. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

[HTA-Perspective: Challenges in the early assessment of new oncological drugs].

PubMed

Wild, Claudia; Nachtnebel, Anna

2013-01-01

Oncologic drug therapies have gained wide attention in the context of health policy priority setting for serious and socially significant diseases with high human and monetary costs. Due to uncertainties and scepticism about the actual therapeutic importance of newly approved oncology products, an early assessment programme was already established in Austria in 2007. The assessment of new oncology products is thereby faced with special challenges, since study populations are frequently not representative or the study design is laid out in such a manner that a definitive assessment of patient-relevant endpoints is not possible (cross-overs after interim assessments, surrogate parameters as primary endpoints, uncontrolled studies or those with unrealistic comparators, invalidated post-hoc identified biomarkers). On account of these major uncertainties, even the European Medicines Agency (EMA) is already contemplating multi-stage, "adaptive" approvals, and national reimbursement institutions are increasingly working with outcome-oriented, conditional reimbursement. (As supplied by publisher). Copyright © 2013. Published by Elsevier GmbH.

Effects of physical and mental stressors on muscle pain.

PubMed

Westgaard, R H

1999-01-01

Physical and mental stressors as risk factors for pain development are discussed. These multifaceted stressor terms are narrowed down so that physical stressors are represented by muscle activity recorded by electromyography (EMG), while mental stress is considered synonymous with psychosocial stress in vocational studies; in experimental studies cognitive stress is used as a model. Pain in the shoulder and neck are focused and related to EMG recordings of activity in the trapezius muscle. Major challenges in this field include proper risk assessment at low physical work loads and criteria for evaluating stress as a risk factor. A 3-factor conceptual model is presented in which the independent dimensions physical work load, mental stress, and individual sensitivity determine the risk of shoulder and neck complaints. It is pointed out that a predominant reduction in physical work load for many jobs and an increasing interaction between work conditions and the general life situation of workers pose particular challenges for risk assessment.

Outcome for the extremely premature neonate: how far do we push the edge?

PubMed

Boat, Anne C; Sadhasivam, Senthilkumar; Loepke, Andreas W; Kurth, Charles D

2011-07-01

Significant advances in perinatal and neonatal medicine over the last 20 years and the recent emergence of fetal surgery has resulted in anesthesia providers caring for a growing number of infants born at the margin of viability. Anesthetic management in this patient population has to take into consideration the immature function of many vital organ systems as well as the effects of the underlying disease processes, which can frequently lead to severe physiological derangements. Accordingly, premature infants presenting for major surgeries early in life can represent a significant anesthetic challenge. However, even with advanced anesthetic and surgical management and optimal intensive care, extremely premature infants face substantial postoperative morbidity and mortality, as well as prolonged hospital courses. In this article, we will discuss the following questions: How far have we come in improving outcomes of extreme prematurity? And what will the future medical and societal challenges be, as we continue to redefine the limits of viability? © 2011 Blackwell Publishing Ltd.

Genetic resistance: tolerance to vector-borne diseases and the prospects and challenges of genomics.

PubMed

Bahbahani, H; Hanotte, O

2015-04-01

Vector-borne diseases in cattle and small ruminants (e.g. trypanosomosis, Rift Valley fever and East Coast fever) are associated with major economic losses in tropical countries, and particularly on the African continent. A variety of control strategies (e.g. management, vaccination and/or acaricide treatments) are used to minimise their negative impacts. These strategies are often associated with environmental, technical and/or economic drawbacks. However, several indigenous livestock populations have been reported to show a level of genetic tolerance or resistance to such disease challenges (e.g. trypanotolerant N'Dama cattle and Djallonké sheep). Use of these populations represents a sustainable alternative approach to minimising the negative impact of such infection/infestation on livestock production. This review summarises the current understanding of the genetic control of these adaptations, identifies knowledge gaps and critically examines the possible impacts of genomics approaches to the genetic improvement of tolerance and/or resistance to vector-borne diseases.

Mouse Models of Breast Cancer: Platforms for Discovering Precision Imaging Diagnostics and Future Cancer Medicine.

PubMed

Manning, H Charles; Buck, Jason R; Cook, Rebecca S

2016-02-01

Representing an enormous health care and socioeconomic challenge, breast cancer is the second most common cancer in the world and the second most common cause of cancer-related death. Although many of the challenges associated with preventing, treating, and ultimately curing breast cancer are addressable in the laboratory, successful translation of groundbreaking research to clinical populations remains an important barrier. Particularly when compared with research on other types of solid tumors, breast cancer research is hampered by a lack of tractable in vivo model systems that accurately recapitulate the relevant clinical features of the disease. A primary objective of this article was to provide a generalizable overview of the types of in vivo model systems, with an emphasis primarily on murine models, that are widely deployed in preclinical breast cancer research. Major opportunities to advance precision cancer medicine facilitated by molecular imaging of preclinical breast cancer models are discussed. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

[The certification of advanced therapy medicinal products. A quality label for product development in small and medium-sized enterprises].

PubMed

Berger, A; Schüle, S; Flory, E

2011-07-01

Advanced therapy medicinal products (ATMPs) are gene therapy, cell therapy, and tissue engineered products. To gain access to the market within the European Union, ATMPs must be authorized by the European Commission (EC). Especially for small and medium-sized enterprises (SMEs), the European centralized procedure of marketing authorization that is conducted by the European Medicines Agency (EMA) constitutes a major challenge, because SMEs often have little experience with regulatory procedures and many have limited financial possibilities. To tackle these challenges, a certification procedure exclusively for SMEs and their ATMP development was introduced by the EC. Independently from a marketing authorization application, development and/or production processes can be certified. An issued certificate demonstrates that the respective process meets the current regulatory and scientific requirements of the EMA, representing a valuable milestone for putative investors and licensees. This article highlights the background, the detailed procedure, the minimum requirements, as well as the costs of certification, while giving further noteworthy guidance for interested parties.

Nutrition affects insect susceptibility to Bt toxins

NASA Astrophysics Data System (ADS)

Deans, Carrie A.; Behmer, Spencer T.; Tessnow, Ashley E.; Tamez-Guerra, Patricia; Pusztai-Carey, Marianne; Sword, Gregory A.

2017-01-01

Pesticide resistance represents a major challenge to global food production. The spread of resistance alleles is the primary explanation for observations of reduced pesticide efficacy over time, but the potential for gene-by-environment interactions (plasticity) to mediate susceptibility has largely been overlooked. Here we show that nutrition is an environmental factor that affects susceptibility to Bt toxins. Protein and carbohydrates are two key macronutrients for insect herbivores, and the polyphagous pest Helicoverpa zea self-selects and performs best on diets that are protein-biased relative to carbohydrates. Despite this, most Bt bioassays employ carbohydrate-biased rearing diets. This study explored the effect of diet protein-carbohydrate content on H. zea susceptibility to Cry1Ac, a common Bt endotoxin. We detected a 100-fold increase in LC50 for larvae on optimal versus carbohydrate-biased diets, and significant diet-mediated variation in survival and performance when challenged with Cry1Ac. Our results suggest that Bt resistance bioassays that use ecologically- and physiologically-mismatched diets over-estimate susceptibility and under-estimate resistance.

Vertebrobasilar junction giant aneurysm: Lessons learned from a neurosurgical audit and anatomical investigation.

PubMed

Graziano, Francesca; Ganau, Mario; Russo, Vittorio Maria; Iacopino, Domenico G; Ulm, Arthur John

2015-01-01

The treatment of vascular lesions of the vertebrobasilar junction (VBJ) remains a challenging task in the neurosurgical practice and the gold standard therapy is still under debate. In this article, the authors report a detailed postmortem study of a VBJ giant aneurysm (GA) previously endovascularly treated. Although the decision-making process for the vast majority of neurosurgical treatment can nowadays be accurately carried out during the preoperative planning (i.e., with the aid of neuroimaging fusion protocols, neuronavigation platforms, etc.) meant to maximize the anatomical understanding of the lesions and minimize possible intraprocedural challenges, this postmortem study represents the ultimate essence of neurosurgical audit as the laboratory investigations allowed to reevaluate the clinical history of VBJ GA, and reassess the multiple strategies available for its treatment with a straightforward anatomical perspective. Specifically, the lessons learned through this clinical and laboratory work uphold a great educational value regarding the complex management of those lesions, including the possible role of combined skull base surgical approaches.

Interpreting signals from astrophysical transient experiments.

PubMed

O'Brien, Paul T; Smartt, Stephen J

2013-06-13

Time-domain astronomy has come of age with astronomers now able to monitor the sky at high cadence, both across the electromagnetic spectrum and using neutrinos and gravitational waves. The advent of new observing facilities permits new science, but the ever-increasing throughput of facilities demands efficient communication of coincident detections and better subsequent coordination among the scientific community so as to turn detections into scientific discoveries. To discuss the revolution occurring in our ability to monitor the Universe and the challenges it brings, on 25-26 April 2012, a group of scientists from observational and theoretical teams studying transients met with representatives of the major international transient observing facilities at the Kavli Royal Society International Centre, UK. This immediately followed the Royal Society Discussion Meeting 'New windows on transients across the Universe' held in London. Here, we present a summary of the Kavli meeting at which the participants discussed the science goals common to the transient astronomy community and analysed how to better meet the challenges ahead as ever more powerful observational facilities come on stream.

Sustainability and in situ monitoring in battery development.

PubMed

Grey, C P; Tarascon, J M

2016-12-20

The development of improved rechargeable batteries represents a major technological challenge for this new century, as batteries constitute the limiting components in the shift from petrol (gasoline) powered to electric vehicles, while also enabling the use of more renewable energy on the grid. To minimize the ecological implications associated with their wider use, we must integrate sustainability of battery materials into our research endeavours, choosing chemistries that have a minimum footprint in nature and that are more readily recycled or integrated into a full circular economy. Sustainability and cost concerns require that we greatly increase the battery lifetime and consider second lives for batteries. As part of this, we must monitor the state of health of batteries continuously during operation to minimize their degradation. It is thus important to push the frontiers of operando techniques to monitor increasingly complex processes. In this Review, we will describe key advances in both more sustainable chemistries and operando techniques, along with some of the remaining challenges and possible solutions, as we personally perceive them.

Major Management Challenges and Program Risks: Small Business Administration

DTIC Science & Technology

2001-01-01

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

Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations from the 2015 Strategic Planning Conference

PubMed Central

Sahin, Mustafa; Henske, Elizabeth P.; Manning, Brendan D.; Ess, Kevin C.; Bissler, John J.; Klann, Eric; Kwiatkowski, David J.; Roberds, Steven L.; Silva, Alcino J.; Hillaire-Clarke, Coryse St.; Young, Lisa R.; Zervas, Mark; Mamounas, Laura A.

2016-01-01

On March 10–12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. This review summarizes outcomes from the extensive pre-meeting deliberations and final workshop recommendations, and includes: 1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex; 2) the key gaps, needs and challenges that hinder progress in tuberous sclerosis complex research; and 3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five- to ten-year timeframe. PMID:27267556

Perception of the Professional Knowledge of and Education on the Medical Technology Products among the Pharmacists in the Baltic and Nordic Countries-A Cross-Sectional Exploratory Study.

PubMed

Volmer, Daisy; Sokirskaja, Aleksandra; Laaksonen, Raisa; Vainio, Kirsti; Sandler, Niklas; Halvorsen, Kjell H; Kjome, Reidun Lisbet Skeide; Gizurarson, Sveinbjörn; Muceniece, Ruta; Maurina, Baiba; Dauksiene, Jurgita; Ruuben, Lilian; Björnsdottir, Ingunn; Ratassepp, Tagne; Heinämäki, Jyrki

2016-10-13

With increased development of medical technology (MT), new challenges emerge related to education and training of pharmacists and other healthcare specialists. Currently, only a few universities in the EU promote MT education and research. The aim of this study was to evaluate the current status, views on, and need for the education on MT for the pharmacy students and practicing pharmacists in the Baltic and Nordic countries. The representatives of higher education institutions and community/hospital pharmacists from six Baltic and Nordic countries participated in a qualitative cross-sectional exploratory internet-based study from May to October 2014. Approximately two-third of the respondents considered professional knowledge about MT products important for pharmacists, but half of them had never participated in any MT courses. More practicing pharmacists than representatives of academia underlined the need for increased MT education for pharmacy students in the future. The pharmacists in the Baltic and Nordic countries consider the professional knowledge about MT as pertinent in their education and work. The limited number and status of MT courses available today, however, is a major concern among both pharmacy students and practicing pharmacists in these countries. In the future, increasing education combining theory and practice about MT products would be one possible solution to overcome this challenge.

Perception of the Professional Knowledge of and Education on the Medical Technology Products among the Pharmacists in the Baltic and Nordic Countries—A Cross-Sectional Exploratory Study

PubMed Central

Volmer, Daisy; Sokirskaja, Aleksandra; Laaksonen, Raisa; Vainio, Kirsti; Sandler, Niklas; Halvorsen, Kjell H.; Kjome, Reidun Lisbet Skeide; Gizurarson, Sveinbjörn; Muceniece, Ruta; Maurina, Baiba; Dauksiene, Jurgita; Ruuben, Lilian; Björnsdottir, Ingunn; Ratassepp, Tagne; Heinämäki, Jyrki

2016-01-01

With increased development of medical technology (MT), new challenges emerge related to education and training of pharmacists and other healthcare specialists. Currently, only a few universities in the EU promote MT education and research. Objectives: The aim of this study was to evaluate the current status, views on, and need for the education on MT for the pharmacy students and practicing pharmacists in the Baltic and Nordic countries. Methods: The representatives of higher education institutions and community/hospital pharmacists from six Baltic and Nordic countries participated in a qualitative cross-sectional exploratory internet-based study from May to October 2014. Results: Approximately two-third of the respondents considered professional knowledge about MT products important for pharmacists, but half of them had never participated in any MT courses. More practicing pharmacists than representatives of academia underlined the need for increased MT education for pharmacy students in the future. Conclusions: The pharmacists in the Baltic and Nordic countries consider the professional knowledge about MT as pertinent in their education and work. The limited number and status of MT courses available today, however, is a major concern among both pharmacy students and practicing pharmacists in these countries. In the future, increasing education combining theory and practice about MT products would be one possible solution to overcome this challenge. PMID:28970402

Health Recommender Systems: Concepts, Requirements, Technical Basics and Challenges

PubMed Central

Wiesner, Martin; Pfeifer, Daniel

2014-01-01

During the last decades huge amounts of data have been collected in clinical databases representing patients' health states (e.g., as laboratory results, treatment plans, medical reports). Hence, digital information available for patient-oriented decision making has increased drastically but is often scattered across different sites. As as solution, personal health record systems (PHRS) are meant to centralize an individual's health data and to allow access for the owner as well as for authorized health professionals. Yet, expert-oriented language, complex interrelations of medical facts and information overload in general pose major obstacles for patients to understand their own record and to draw adequate conclusions. In this context, recommender systems may supply patients with additional laymen-friendly information helping to better comprehend their health status as represented by their record. However, such systems must be adapted to cope with the specific requirements in the health domain in order to deliver highly relevant information for patients. They are referred to as health recommender systems (HRS). In this article we give an introduction to health recommender systems and explain why they are a useful enhancement to PHR solutions. Basic concepts and scenarios are discussed and a first implementation is presented. In addition, we outline an evaluation approach for such a system, which is supported by medical experts. The construction of a test collection for case-related recommendations is described. Finally, challenges and open issues are discussed. PMID:24595212

How to make complexity look simple? Conveying ecosystems restoration complexity for socio-economic research and public engagement

PubMed Central

Glenk, Klaus; Byg, Anja

2017-01-01

Ecosystems degradation represents one of the major global challenges at the present time, threating people’s livelihoods and well-being worldwide. Ecosystem restoration therefore seems no longer an option, but an imperative. Restoration challenges are such that a dialogue has begun on the need to re-shape restoration as a science. A critical aspect of that reshaping process is the acceptance that restoration science and practice needs to be coupled with socio-economic research and public engagement. This inescapably means conveying complex ecosystem’s information in a way that is accessible to the wider public. In this paper we take up this challenge with the ultimate aim of contributing to making a step change in science’s contribution to ecosystems restoration practice. Using peatlands as a paradigmatically complex ecosystem, we put in place a transdisciplinary process to articulate a description of the processes and outcomes of restoration that can be understood widely by the public. We provide evidence of the usefulness of the process and tools in addressing four key challenges relevant to restoration of any complex ecosystem: (1) how to represent restoration outcomes; (2) how to establish a restoration reference; (3) how to cope with varying restoration time-lags and (4) how to define spatial units for restoration. This evidence includes the way the process resulted in the creation of materials that are now being used by restoration practitioners for communication with the public and in other research contexts. Our main contribution is of an epistemological nature: while ecosystem services-based approaches have enhanced the integration of academic disciplines and non-specialist knowledge, this has so far only followed one direction (from the biophysical underpinning to the description of ecosystem services and their appreciation by the public). We propose that it is the mix of approaches and epistemological directions (including from the public to the biophysical parameters) what will make a definitive contribution to restoration practice. PMID:28753629

How to make complexity look simple? Conveying ecosystems restoration complexity for socio-economic research and public engagement.

PubMed

Martin-Ortega, Julia; Glenk, Klaus; Byg, Anja

2017-01-01

Ecosystems degradation represents one of the major global challenges at the present time, threating people's livelihoods and well-being worldwide. Ecosystem restoration therefore seems no longer an option, but an imperative. Restoration challenges are such that a dialogue has begun on the need to re-shape restoration as a science. A critical aspect of that reshaping process is the acceptance that restoration science and practice needs to be coupled with socio-economic research and public engagement. This inescapably means conveying complex ecosystem's information in a way that is accessible to the wider public. In this paper we take up this challenge with the ultimate aim of contributing to making a step change in science's contribution to ecosystems restoration practice. Using peatlands as a paradigmatically complex ecosystem, we put in place a transdisciplinary process to articulate a description of the processes and outcomes of restoration that can be understood widely by the public. We provide evidence of the usefulness of the process and tools in addressing four key challenges relevant to restoration of any complex ecosystem: (1) how to represent restoration outcomes; (2) how to establish a restoration reference; (3) how to cope with varying restoration time-lags and (4) how to define spatial units for restoration. This evidence includes the way the process resulted in the creation of materials that are now being used by restoration practitioners for communication with the public and in other research contexts. Our main contribution is of an epistemological nature: while ecosystem services-based approaches have enhanced the integration of academic disciplines and non-specialist knowledge, this has so far only followed one direction (from the biophysical underpinning to the description of ecosystem services and their appreciation by the public). We propose that it is the mix of approaches and epistemological directions (including from the public to the biophysical parameters) what will make a definitive contribution to restoration practice.

A memetic optimization algorithm for multi-constrained multicast routing in ad hoc networks

PubMed Central

Hammad, Karim; El Bakly, Ahmed M.

2018-01-01

A mobile ad hoc network is a conventional self-configuring network where the routing optimization problem—subject to various Quality-of-Service (QoS) constraints—represents a major challenge. Unlike previously proposed solutions, in this paper, we propose a memetic algorithm (MA) employing an adaptive mutation parameter, to solve the multicast routing problem with higher search ability and computational efficiency. The proposed algorithm utilizes an updated scheme, based on statistical analysis, to estimate the best values for all MA parameters and enhance MA performance. The numerical results show that the proposed MA improved the delay and jitter of the network, while reducing computational complexity as compared to existing algorithms. PMID:29509760

A memetic optimization algorithm for multi-constrained multicast routing in ad hoc networks.

PubMed

Ramadan, Rahab M; Gasser, Safa M; El-Mahallawy, Mohamed S; Hammad, Karim; El Bakly, Ahmed M

2018-01-01

A mobile ad hoc network is a conventional self-configuring network where the routing optimization problem-subject to various Quality-of-Service (QoS) constraints-represents a major challenge. Unlike previously proposed solutions, in this paper, we propose a memetic algorithm (MA) employing an adaptive mutation parameter, to solve the multicast routing problem with higher search ability and computational efficiency. The proposed algorithm utilizes an updated scheme, based on statistical analysis, to estimate the best values for all MA parameters and enhance MA performance. The numerical results show that the proposed MA improved the delay and jitter of the network, while reducing computational complexity as compared to existing algorithms.

GDRMS: a system for automatic extraction of the disease-centre relation

NASA Astrophysics Data System (ADS)

Yang, Ronggen; Zhang, Yue; Gong, Lejun

2012-01-01

With the rapidly increasing of biomedical literature, the deluge of new articles is leading to information overload. Extracting the available knowledge from the huge amount of biomedical literature has become a major challenge. GDRMS is developed as a tool that extracts the relationship between disease and gene, gene and gene from biomedical literatures using text mining technology. It is a ruled-based system which also provides disease-centre network visualization, constructs the disease-gene database, and represents a gene engine for understanding the function of the gene. The main focus of GDRMS is to provide a valuable opportunity to explore the relationship between disease and gene for the research community about etiology of disease.

A(H5N1) Virus Evolution in South East Asia

PubMed Central

Gutiérrez, Ramona Alikiiteaga; Naughtin, Monica Jane; Horm, Srey Viseth; San, Sorn; Buchy, Philippe

2009-01-01

Highly Pathogenic Avian Influenza (HPAI) H5N1 virus is an ongoing public health and socio-economic challenge, particularly in South East Asia. H5N1 is now endemic in poultry in many countries, and represents a major pandemic threat. Here, we describe the evolution of H5N1 virus in South East Asia, the reassortment events leading to high genetic diversity in the region, and factors responsible for virus spread. The virus has evolved with genetic variations affecting virulence, drug-resistance, and adaptation to new host species. The constant surveillance of these changes is of primary importance in the global efforts of the scientific community. PMID:21994553

Disruption or Excision of Provirus as an Approach to HIV Cure.

PubMed

Jerome, Keith R

2016-12-01

An effective approach to HIV cure will almost certainly require a combination of strategies, including some means of reducing the latent HIV reservoir. Because the integrated HIV provirus represents the major source of viral persistence and reactivation, one attractive approach is the direct targeting of provirus for disruption or excision using targeted endonucleases, such as CRISPR/Cas9, zinc finger nucleases, TAL effector nucleases, or meganucleases (homing endonucleases). This article highlights some of the challenges for successful endonuclease therapy for HIV, including optimization of enzyme activity and specificity, the possible emergence of viral resistance, and most importantly, efficient in vivo delivery of the enzymes to a sufficient portion of the latent reservoir.

[Establishing Individualized Medicine for Intractable Cancer Based on Clinical Molecular Pathogenesis].

PubMed

Jono, Hirofumi

2018-01-01

　Although cancer treatment has dramatically improved with the development of molecular-targeted agents over the past decade, identifying eligible patients and predicting the therapeutic effects remain a major challenge. Because intratumoral heterogeneity represents genetic and molecular differences affecting patients' responses to these therapeutic agents, establishing individualized medicine based on precise molecular pathological analysis of tumors is urgently required. This review focuses on the pathogenesis of oral squamous cell carcinoma (OSCC), a common head and neck neoplasm, and introduces our approaches toward developing novel anticancer therapies particularly based on clinical molecular pathogenesis. Deeper understanding of more precise molecular pathogenesis in clinical settings may open up novel strategies for establishing individualized medicine for OSCC.

Supervised Semantic Classification for Nuclear Proliferation Monitoring

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

Vatsavai, Raju; Cheriyadat, Anil M; Gleason, Shaun Scott

2010-01-01

Existing feature extraction and classification approaches are not suitable for monitoring proliferation activity using high-resolution multi-temporal remote sensing imagery. In this paper we present a supervised semantic labeling framework based on the Latent Dirichlet Allocation method. This framework is used to analyze over 120 images collected under different spatial and temporal settings over the globe representing three major semantic categories: airports, nuclear, and coal power plants. Initial experimental results show a reasonable discrimination of these three categories even though coal and nuclear images share highly common and overlapping objects. This research also identified several research challenges associated with nuclear proliferationmore » monitoring using high resolution remote sensing images.« less

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

Human Factors Engineering and testing for a wearable, long duration ultrasound system self-applied by an end user.

PubMed

Taggart, Rebecca; Langer, Matthew D; Lewis, George K

2014-01-01

One of the major challenges in the design of a new class of medical device is ensuring that the device will have a safe and effective user interface for the intended users. Human Factors Engineering addresses these concerns through direct study of how a user interacts with newly designed devices with unique features. In this study, a novel long duration, low intensity therapeutic ultrasound device is tested by 20 end users representative of the intended user population. Over 90% of users were able to operate the device successfully. The therapeutic ultrasound device was found to be reasonably safe and effective for the intended users, uses, and use environments.

Predicting nutrient responses to mitigation at catchment to national scale: the UK research platform (Invited)

NASA Astrophysics Data System (ADS)

Johnes, P.

2013-12-01

Nutrient enrichment of waters from land-based and atmospheric sources presents a significant management challenge, requiring effective stakeholder engagement and policy development, properly underpinned by robust scientific evidence. The challenge is complex, raising significant questions about the specific sources, apportionment and pathways that determine nutrient enrichment and the key priorities for effective management and policy intervention. This paper presents outputs from 4 major UK research programmes: the Defra Demonstration Test Catchments programme (DTC), the Environment Agency's Catchment Sensitive Farming monitoring and evaluation programme (CSF), Natural Resources Wales Welsh Catchment Initiative (WCI) and the NERC Environmental Virtual Observatory programme (EVOp). Funded to meet this challenge, they are delivering new understanding of the rates and sources of pollutant fluxes from land to water, their impacts on ecosystem goods and services, and likely trends under future climate and land use change from field to national scale. DTC, a 12m investment by the UK Government, has set up long-term, high resolution research platforms equipped with novel telemetered sensor networks to monitor stream ecosystem responses to on-farm mitigation measures at a representative scale for catchment management. Ecosystem structural and functional responses and bulk hydrochemistry are also being monitored using standard protocols. CSF has set up long-term, enhanced monitoring in 8 priority catchments, with monthly monitoring in a further 72 English catchments and 6 Welsh priority catchments, to identify shifts in pollutant flux to waters resulting from mitigation measures in priority areas and farming sectors. CSF and WCI have contributed to >50 million of targeted farm improvements to date, representing a significant shift in farming practice. Each programme has generated detailed evidence on stream ecosystem responses to targeted mitigation. However, to provide effective underpinning for policy the major challenge has been to upscale this knowledge beyond these data-rich systems and identify the dominant contributing areas and priorities for management intervention to control nutrient flux and ecological impacts in data-poor systems which are located downstream from existing monitoring infrastructure or are in unmonitored catchments in remote locations. EVOp has directly addressed this challenge, developing a cloud computing enabled National Biogeochemical Modelling Framework to support ensemble modelling, knowledge capture and transfer from DTC, CSF, WCI and data-rich research catchments. This platform provides opportunities for further development of national biogeochemical modelling capability, allowing upscaled predictions from plot to catchment and national scale, enabling knowledge transfer from data-rich to data-poor areas. This paper presents initial findings from these research platforms, identifying the key priorities for action emerging from our national scale scenario analysis, and future research directions to further improve understanding, prediction and management capability in nutrient enriched waters and their catchments under changing climate and land use.

Genome-Wide Diversity and Phylogeography of Mycobacterium avium subsp. paratuberculosis in Canadian Dairy Cattle

PubMed Central

Ahlstrom, Christina; Barkema, Herman W.; Stevenson, Karen; Zadoks, Ruth N.; Biek, Roman; Kao, Rowland; Trewby, Hannah; Haupstein, Deb; Kelton, David F.; Fecteau, Gilles; Labrecque, Olivia; Keefe, Greg P.; McKenna, Shawn L. B.; Tahlan, Kapil; De Buck, Jeroen

2016-01-01

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative bacterium of Johne’s disease (JD) in ruminants. The control of JD in the dairy industry is challenging, but can be improved with a better understanding of the diversity and distribution of MAP subtypes. Previously established molecular typing techniques used to differentiate MAP have not been sufficiently discriminatory and/or reliable to accurately assess the population structure. In this study, the genetic diversity of 182 MAP isolates representing all Canadian provinces was compared to the known global diversity, using single nucleotide polymorphisms identified through whole genome sequencing. MAP isolates from Canada represented a subset of the known global diversity, as there were global isolates intermingled with Canadian isolates, as well as multiple global subtypes that were not found in Canada. One Type III and six “Bison type” isolates were found in Canada as well as one Type II subtype that represented 86% of all Canadian isolates. Rarefaction estimated larger subtype richness in Québec than in other Canadian provinces using a strict definition of MAP subtypes and lower subtype richness in the Atlantic region using a relaxed definition. Significant phylogeographic clustering was observed at the inter-provincial but not at the intra-provincial level, although most major clades were found in all provinces. The large number of shared subtypes among provinces suggests that cattle movement is a major driver of MAP transmission at the herd level, which is further supported by the lack of spatial clustering on an intra-provincial scale. PMID:26871723

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

ERIC Educational Resources Information Center

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

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

Foreground Subtraction and Signal reconstruction in redshifted 21cm Global Signal Experiments using Artificial Neural Networks

NASA Astrophysics Data System (ADS)

Choudhury, Madhurima; Datta, Abhirup

2018-05-01

Observations of HI 21cm transition line is a promising probe into the Dark Ages and Epoch-of-Reionization. Detection of this redshifted 21cm signal is one of the key science goal for several upcoming low-frequency radio telescopes like HERA, SKA and DARE. Other global signal experiments include EDGES, LEDA, BIGHORNS, SCI-HI, SARAS. One of the major challenges for the detection of this signal is the accuracy of the foreground source removal. Several novel techniques have been explored already to remove bright foregrounds from both interferometric as well as total power experiments. Here, we present preliminary results from our investigation on application of ANN to detect 21cm global signal amidst bright galactic foreground. Following the formalism of representing the global 21cm signal by 'tanh' model, this study finds that the global 21cm signal parameters can be accurately determined even in the presence of bright foregrounds represented by 3rd order log-polynomial or higher.

Biological aspects of chondrosarcoma: Leaps and hurdles.

PubMed

Mery, Benoîte; Espenel, Sophie; Guy, Jean-Baptiste; Rancoule, Chloé; Vallard, Alexis; Aloy, Marie-Thérèse; Rodriguez-Lafrasse, Claire; Magné, Nicolas

2018-06-01

Chondrosarcomas are characterized by their chemo- and radioresistance leading to a therapeutic surgical approach which remains the only available treatment with a 10-year survival between 30% and 80% depending on the grade. Non-surgical treatments are under investigation and rely on an accurate biological understanding of drug resistance mechanisms. Novel targeted therapy which represents a new relevant therapeutic approach will open new treatment options by targeting several pathways responsible for processes of proliferation and invasion. Survival pathways such as PI3K, AKT, mTOR and VEGF have been shown to be involved in proliferation of chondrosarcoma cells and antiapoptotic proteins may also play a relevant role. Other proteins such as p53 or COX2 have been identified as potential new targets. This review provides an insight into the biological substantial treatment challenges of CHS and focuses on improving our understanding of CH biology through an overview of major signaling pathways that could represent targets for new therapeutic approaches. Copyright © 2018 Elsevier B.V. All rights reserved.

PubMed Central

Vobecky, Jitka S.

1982-01-01

Almost 60% of food additives are colorings, flavorings and other appearance enhancers. Growth of the world's population and growth in demand for food represent the greatest technological challenge of our era. Consequently, usage of substances which preserve the quality and diminish spoilage of food is of prime importance. Nevertheless, the consumer fears that the cumulative effect of additives can lead to cancer, hyperkinesis or other disorders. Given the widespread use of additives, their impact on the health of populations is difficult to study even if certain observed differences between countries are attributed to their diet. Additives introduced during the last few years have satisfied rigorous testing—to which the majority of natural products are not submitted. In contrast, overeating, inactivity, excess saturated fat, alcohol and cigarets are still prevalent, even though the health risks they represent are clearly established. Seeing that the doctor is an authority on health matters, his or her contribution in dispensing information on nutrition and health is important in the battle against fear without scientific proof. PMID:21286202

[Considering housing arrangements in elderly life: factors influencing plans concerning future housing arrangements and preferences in a representative sample of 45+ year olds].

PubMed

Spangenberg, L; Glaesmer, H; Brähler, E; Kersting, A; Strauß, B

2013-04-01

Providing care and support for the elderly is a future challenge. Using regression analysis, a representative population-based sample (n = 1,445) was examined with respect to whether they had considered future housing and which variables influenced their thoughts and preferences. The majority of the sample reported thinking about housing in old age and preferred to stay at home in old age. Thoughts about future housing and housing preferences were predicted by different factors in the age groups analyzed. Thinking about future housing was positively associated with increasing age and depression. Other relevant predictors were gender, living with a partner, images of old age (especially negative ones), and anticipated subjective health. These variables also predicted housing preferences. Thoughts about future living arrangements are widespread, and their importance increases with age. The wishes reported do contrast to a certain extent with reality. Planning future care as well as developing consultation guidelines should address these issues while considering the reported influences.

Scaffold optimization in discontinuous epitope containing protein mimics of gp120 using smart libraries.

PubMed

Mulder, Gwenn E; Quarles van Ufford, H Linda C; van Ameijde, Jeroen; Brouwer, Arwin J; Kruijtzer, John A W; Liskamp, Rob M J

2013-04-28

A diversity of protein surface discontinuous epitope mimics is now rapidly and efficiently accessible. Despite the important role of protein-protein interactions involving discontinuous epitopes in a wide range of diseases, mimicry of discontinuous epitopes using peptide-based molecules remains a major challenge. Using copper(I) catalyzed azide-alkyne cycloaddition (CuAAC), we have developed a general and efficient method for the synthesis of collections of discontinuous epitope mimics. Up to three different cyclic peptides, representing discontinuous epitopes in HIV-gp120, were conjugated to a selection of scaffold molecules. Variation of the scaffold molecule, optimization of the ring size of the cyclic peptides and screening of the resulting libraries for successful protein mimics led to an HIV gp120 mimic with an IC50 value of 1.7 μM. The approach described here provides rapid and highly reproducible access to clean, smart libraries of very complex bio-molecular constructs representing protein mimics for use as synthetic vaccines and beyond.

Proposal for a biometrics of the cortical surface: a statistical method for relative surface distance metrics

NASA Astrophysics Data System (ADS)

Bookstein, Fred L.

1995-08-01

Recent advances in computational geometry have greatly extended the range of neuroanatomical questions that can be approached by rigorous quantitative methods. One of the major current challenges in this area is to describe the variability of human cortical surface form and its implications for individual differences in neurophysiological functioning. Existing techniques for representation of stochastically invaginated surfaces do not conduce to the necessary parametric statistical summaries. In this paper, following a hint from David Van Essen and Heather Drury, I sketch a statistical method customized for the constraints of this complex data type. Cortical surface form is represented by its Riemannian metric tensor and averaged according to parameters of a smooth averaged surface. Sulci are represented by integral trajectories of the smaller principal strains of this metric, and their statistics follow the statistics of that relative metric. The diagrams visualizing this tensor analysis look like alligator leather but summarize all aspects of cortical surface form in between the principal sulci, the reliable ones; no flattening is required.

Selective oxidation of aliphatic C-H bonds in alkylphenols by a chemomimetic biocatalytic system.

PubMed

Du, Lei; Dong, Sheng; Zhang, Xingwang; Jiang, Chengying; Chen, Jingfei; Yao, Lishan; Wang, Xiao; Wan, Xiaobo; Liu, Xi; Wang, Xinquan; Huang, Shaohua; Cui, Qiu; Feng, Yingang; Liu, Shuang-Jiang; Li, Shengying

2017-06-27

Selective oxidation of aliphatic C-H bonds in alkylphenols serves significant roles not only in generation of functionalized intermediates that can be used to synthesize diverse downstream chemical products, but also in biological degradation of these environmentally hazardous compounds. Chemo-, regio-, and stereoselectivity; controllability; and environmental impact represent the major challenges for chemical oxidation of alkylphenols. Here, we report the development of a unique chemomimetic biocatalytic system originated from the Gram-positive bacterium Corynebacterium glutamicum The system consisting of CreHI (for installation of a phosphate directing/anchoring group), CreJEF/CreG/CreC (for oxidation of alkylphenols), and CreD (for directing/anchoring group offloading) is able to selectively oxidize the aliphatic C-H bonds of p - and m -alkylated phenols in a controllable manner. Moreover, the crystal structures of the central P450 biocatalyst CreJ in complex with two representative substrates provide significant structural insights into its substrate flexibility and reaction selectivity.

Selective oxidation of aliphatic C–H bonds in alkylphenols by a chemomimetic biocatalytic system

PubMed Central

Du, Lei; Dong, Sheng; Zhang, Xingwang; Jiang, Chengying; Chen, Jingfei; Yao, Lishan; Wang, Xiao; Wan, Xiaobo; Liu, Xi; Wang, Xinquan; Huang, Shaohua; Cui, Qiu; Liu, Shuang-Jiang; Li, Shengying

2017-01-01

Selective oxidation of aliphatic C–H bonds in alkylphenols serves significant roles not only in generation of functionalized intermediates that can be used to synthesize diverse downstream chemical products, but also in biological degradation of these environmentally hazardous compounds. Chemo-, regio-, and stereoselectivity; controllability; and environmental impact represent the major challenges for chemical oxidation of alkylphenols. Here, we report the development of a unique chemomimetic biocatalytic system originated from the Gram-positive bacterium Corynebacterium glutamicum. The system consisting of CreHI (for installation of a phosphate directing/anchoring group), CreJEF/CreG/CreC (for oxidation of alkylphenols), and CreD (for directing/anchoring group offloading) is able to selectively oxidize the aliphatic C–H bonds of p- and m-alkylated phenols in a controllable manner. Moreover, the crystal structures of the central P450 biocatalyst CreJ in complex with two representative substrates provide significant structural insights into its substrate flexibility and reaction selectivity. PMID:28607077

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

ERIC Educational Resources Information Center

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

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

Non-parametric transient classification using adaptive wavelets

NASA Astrophysics Data System (ADS)

Varughese, Melvin M.; von Sachs, Rainer; Stephanou, Michael; Bassett, Bruce A.

2015-11-01

Classifying transients based on multiband light curves is a challenging but crucial problem in the era of GAIA and Large Synoptic Sky Telescope since the sheer volume of transients will make spectroscopic classification unfeasible. We present a non-parametric classifier that predicts the transient's class given training data. It implements two novel components: the use of the BAGIDIS wavelet methodology - a characterization of functional data using hierarchical wavelet coefficients - as well as the introduction of a ranked probability classifier on the wavelet coefficients that handles both the heteroscedasticity of the data in addition to the potential non-representativity of the training set. The classifier is simple to implement while a major advantage of the BAGIDIS wavelets is that they are translation invariant. Hence, BAGIDIS does not need the light curves to be aligned to extract features. Further, BAGIDIS is non-parametric so it can be used effectively in blind searches for new objects. We demonstrate the effectiveness of our classifier against the Supernova Photometric Classification Challenge to correctly classify supernova light curves as Type Ia or non-Ia. We train our classifier on the spectroscopically confirmed subsample (which is not representative) and show that it works well for supernova with observed light-curve time spans greater than 100 d (roughly 55 per cent of the data set). For such data, we obtain a Ia efficiency of 80.5 per cent and a purity of 82.4 per cent, yielding a highly competitive challenge score of 0.49. This indicates that our `model-blind' approach may be particularly suitable for the general classification of astronomical transients in the era of large synoptic sky surveys.

Rhabdomyosarcoma: Current Challenges and Their Implications for Developing Therapies

PubMed Central

Hettmer, Simone; Li, Zhizhong; Billin, Andrew N.; Barr, Frederic G.; Cornelison, D.D.W.; Ehrlich, Alan R.; Guttridge, Denis C.; Hayes-Jordan, Andrea; Helman, Lee J.; Houghton, Peter J.; Khan, Javed; Langenau, David M.; Linardic, Corinne M.; Pal, Ranadip; Partridge, Terence A.; Pavlath, Grace K.; Rota, Rossella; Schäfer, Beat W.; Shipley, Janet; Stillman, Bruce; Wexler, Leonard H.; Wagers, Amy J.; Keller, Charles

2014-01-01

Rhabdomyosarcoma (RMS) represents a rare, heterogeneous group of mesodermal malignancies with skeletal muscle differentiation. One major subgroup of RMS tumors (so-called “fusion-positive” tumors) carries exclusive chromosomal translocations that join the DNA-binding domain of the PAX3 or PAX7 gene to the transactivation domain of the FOXO1 (previously known as FKHR) gene. Fusion-negative RMS represents a heterogeneous spectrum of tumors with frequent RAS pathway activation. Overtly metastatic disease at diagnosis is more frequently found in individuals with fusion-positive than in those with fusion-negative tumors. RMS is the most common pediatric soft-tissue sarcoma, and approximately 60% of all children and adolescents diagnosed with RMS are cured by currently available multimodal therapies. However, a curative outcome is achieved in <30% of high-risk individuals with RMS, including all those diagnosed as adults, those diagnosed with fusion-positive tumors during childhood (including metastatic and nonmetastatic tumors), and those diagnosed with metastatic disease during childhood (including fusion-positive and fusion-negative tumors). This white paper outlines current challenges in RMS research and their implications for developing more effective therapies. Urgent clinical problems include local control, systemic disease, need for improved risk stratification, and characterization of differences in disease course in children and adults. Biological challenges include definition of the cellular functions of PAX-FOXO1 fusion proteins, clarification of disease heterogeneity, elucidation of the cellular origins of RMS, delineation of the tumor microenvironment, and identification of means for rational selection and testing of new combination therapies. To streamline future therapeutic developments, it will be critical to improve access to fresh tumor tissue for research purposes, consider alternative trial designs to optimize early clinical testing of candidate drugs, coalesce advocacy efforts to garner public and industry support, and facilitate collaborative efforts between academia and industry. PMID:25368019

Peyronie's disease intervention trials: methodological challenges and issues.

PubMed

Müller, Alexander; Mulhall, John P

2009-03-01

Peyronie's Disease (PD) has been studied for more than 260 years since Francois de la Peyronie's description in 1743. Based on the current literature, the prevalence of PD seems 3-9% with an average age of onset in the fifth life decade. Much effort has been spent on developing nonsurgical treatment options to cure or at least prevent disease progression. The recent examination of drug trials for erectile dysfunction has led us to assess PD trial methodology more closely. An Iinternet search on PubMed was performed using MeSH words PD, clinical trials, oral, transdermal, intralesional and shock wave therapy focusing on 26 representing studies published over the last 15 years. Mean Outcome Measures. A comprehensive review of the current literature on nonsurgical treatment options for PD was conducted to address methodological issues and challenges in PD trials highlighting trial design, patient population, and symptom and sign assessment. The majority of the reviewed studies are underpowered and the heterogeneity in the methodological approach and patient assessment between the studies is one of the remarkable findings from our review. Studies should use a uniform means of defining the degree and type of penile deformity and a large enough cohort of patients should be studied for adequate study power. An ideally designed PD intervention trial should comprise: (i) a randomized, placebo-controlled design; (ii) with a PD patient set representative of the general PD population; and (iii) a comprehensive symptom and sign assessment before and at the end of treatment which includes an assessment of at least deformity, pain, and sexual function. A number of challenges exist for the design of PD intervention trials and deciphering the data generated from them. The field would benefit greatly from a consensus statement or guidelines development on the design and conduct of such trials.

Query by example video based on fuzzy c-means initialized by fixed clustering center

NASA Astrophysics Data System (ADS)

Hou, Sujuan; Zhou, Shangbo; Siddique, Muhammad Abubakar

2012-04-01

Currently, the high complexity of video contents has posed the following major challenges for fast retrieval: (1) efficient similarity measurements, and (2) efficient indexing on the compact representations. A video-retrieval strategy based on fuzzy c-means (FCM) is presented for querying by example. Initially, the query video is segmented and represented by a set of shots, each shot can be represented by a key frame, and then we used video processing techniques to find visual cues to represent the key frame. Next, because the FCM algorithm is sensitive to the initializations, here we initialized the cluster center by the shots of query video so that users could achieve appropriate convergence. After an FCM cluster was initialized by the query video, each shot of query video was considered a benchmark point in the aforesaid cluster, and each shot in the database possessed a class label. The similarity between the shots in the database with the same class label and benchmark point can be transformed into the distance between them. Finally, the similarity between the query video and the video in database was transformed into the number of similar shots. Our experimental results demonstrated the performance of this proposed approach.

Transfer learning improves supervised image segmentation across imaging protocols.

PubMed

van Opbroek, Annegreet; Ikram, M Arfan; Vernooij, Meike W; de Bruijne, Marleen

2015-05-01

The variation between images obtained with different scanners or different imaging protocols presents a major challenge in automatic segmentation of biomedical images. This variation especially hampers the application of otherwise successful supervised-learning techniques which, in order to perform well, often require a large amount of labeled training data that is exactly representative of the target data. We therefore propose to use transfer learning for image segmentation. Transfer-learning techniques can cope with differences in distributions between training and target data, and therefore may improve performance over supervised learning for segmentation across scanners and scan protocols. We present four transfer classifiers that can train a classification scheme with only a small amount of representative training data, in addition to a larger amount of other training data with slightly different characteristics. The performance of the four transfer classifiers was compared to that of standard supervised classification on two magnetic resonance imaging brain-segmentation tasks with multi-site data: white matter, gray matter, and cerebrospinal fluid segmentation; and white-matter-/MS-lesion segmentation. The experiments showed that when there is only a small amount of representative training data available, transfer learning can greatly outperform common supervised-learning approaches, minimizing classification errors by up to 60%.

Hematopoietic and mesenchymal stem cells for the treatment of chronic respiratory diseases: role of plasticity and heterogeneity.

PubMed

Conese, Massimo; Piro, Donatella; Carbone, Annalucia; Castellani, Stefano; Di Gioia, Sante

2014-01-01

Chronic lung diseases, such as cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD) are incurable and represent a very high social burden. Stem cell-based treatment may represent a hope for the cure of these diseases. In this paper, we revise the overall knowledge about the plasticity and engraftment of exogenous marrow-derived stem cells into the lung, as well as their usefulness in lung repair and therapy of chronic lung diseases. The lung is easily accessible and the pathophysiology of these diseases is characterized by injury, inflammation, and eventually by remodeling of the airways. Bone marrow-derived stem cells, including hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stromal (stem) cells (MSCs), encompass a wide array of cell subsets with different capacities of engraftment and injured tissue regenerating potential. Proof-of-principle that marrow cells administered locally may engraft and give rise to specialized epithelial cells has been given, but the efficiency of this conversion is too limited to give a therapeutic effect. Besides the identification of plasticity mechanisms, the characterization/isolation of the stem cell subpopulations represents a major challenge to improving the efficacy of transplantation protocols used in regenerative medicine for lung diseases.

The economic burden of diabetes to French national health insurance: a new cost-of-illness method based on a combined medicalized and incremental approach.

PubMed

de Lagasnerie, Grégoire; Aguadé, Anne-Sophie; Denis, Pierre; Fagot-Campagna, Anne; Gastaldi-Menager, Christelle

2018-03-01

A better understanding of the economic burden of diabetes constitutes a major public health challenge in order to design new ways to curb diabetes health care expenditure. The aim of this study was to develop a new cost-of-illness method in order to assess the specific and nonspecific costs of diabetes from a public payer perspective. Using medical and administrative data from the major French national health insurance system covering about 59 million individuals in 2012, we identified people with diabetes and then estimated the economic burden of diabetes. Various methods were used: (a) global cost of patients with diabetes, (b) cost of treatment directly related to diabetes (i.e., 'medicalized approach'), (c) incremental regression-based approach, (d) incremental matched-control approach, and (e) a novel combination of the 'medicalized approach' and the 'incremental matched-control' approach. We identified 3 million individuals with diabetes (5% of the population). The total expenditure of this population amounted to €19 billion, representing 15% of total expenditure reimbursed to the entire population. Of the total expenditure, €10 billion (52%) was considered to be attributable to diabetes care: €2.3 billion (23% of €10 billion) was directly attributable, and €7.7 billion was attributable to additional reimbursed expenditure indirectly related to diabetes (77%). Inpatient care represented the major part of the expenditure attributable to diabetes care (22%) together with drugs (20%) and medical auxiliaries (15%). Antidiabetic drugs represented an expenditure of about €1.1 billion, accounting for 49% of all diabetes-specific expenditure. This study shows the economic impact of the assumption concerning definition of costs on evaluation of the economic burden of diabetes. The proposed new cost-of-illness method provides specific insight for policy-makers to enhance diabetes management and assess the opportunity costs of diabetes complications' management programs.

Stability validation of paraformaldehyde-fixed samples for the assessment of the platelet PECAM-1, P-selectin, and PAR-1 thrombin receptor by flow cytometry.

PubMed

Atar, Oliver D; Eisert, Christian; Pokov, Ilya; Serebruany, Victor L

2010-07-01

Sample fixation for storage and/or transportation represents an unsolved challenge for multicenter clinical trials assessing serial changes in platelet activity, or monitoring various antiplatelet regimens. Whole blood flow cytometry represents a major advance in defining platelet function, although special training and expensive equipment is required. We sought to determine how fixation with 2% paraformaldehyde (PFA), and storage of blood samples over 1 week affects the flow cytometry readings for both intact and thrombin-activating four major surface platelet receptors. Whole blood platelet expression of PECAM-1, P-selectin, PAR-1 inactive receptor (SPAN-12), and cleaved (WEDE-15) epitope was assessed immediately after blood draw, after staining with 2% PFA, and at day 1, 3, 5, and 7. The study was performed in 6 volunteers with multiple risk factors for vascular disease, not receiving any antiplatelet agents. Staining with PFA resulted in a slight decrease of fluorescence intensity, especially for PECAM-1, while antigen expression at day 1, 3 and 5 remains consistent, and highly reproducible. At day 7 there was a small but inconsistent trend towards diminished fluorescence intensity. The platelet data were consistent while validated with the isotype-matched irrelevant antibody. These data suggest that there is a 5 day window to perform final flow cytometry readings of whole blood PFA-fixed inactivated platelet samples. In contrast, thrombin activation cause gradual loss of flow cytometry signal, and cannot be recommended for long-term storage. This is critical logistic information for conducting multicenter platelet substudies within the framework of major clinical trials.

Organisational justice and employee perceptions on hospital management.

PubMed

Wiili-Peltola, Erja; Kivimäki, Mika; Elovainio, Marko; Virtanen, Marianna

2007-01-01

The purpose to clarify what kind of managerial challenges employees experience regarding organisational justice in hospitals. This exploratory study of 8,971 employees working in 14 hospitals and examines the concept of organisational justice in management with qualitative and quantitative methods. An inductive content analysis of the comments revealed five integrative frames describing challenges in hospital management at respondents' workplaces. These frames should be regarded as major managerial challenges in hospitals. These findings illustrate important antecedents of organisational justice and suggest that work units tend to share the same perceptions of justice. They also reveal that individually produced comments reflect collective experiences in organisational justice. Further, the results indicate that problems in management and policies are often experienced in a complex way, and people making justice judgements do not separate procedural and interactional factors. Although the commentators producing qualitative data represented many organisational hierarchy levels, the results should not be generalised to apply to horizontal, informal social relationships. This paper gives useful information regarding challenges in human resources management in hospitals. The paper suggests that people making fairness judgements do not make a distinction between procedural and interpersonal factors. Instead, they use any information available to judge the righteousness of the management events. This paper serves to guide hospital managers towards a better understanding of the importance of organisational justice and its collective nature.

Challenges in Parameterizing the Lifecycle of Cumulus Convection in Global Climate Models

NASA Astrophysics Data System (ADS)

Del Genio, A. D.

2012-12-01

Moist convection exerts a strong influence on Earth's general circulation, energy cycle, and water cycle and has long been considered among the most difficult processes to represent in global climate models. Historically, convection has been portrayed in models as a collection of individual cells, and most of the attention has focused on deep precipitating convection that adjusts quickly to large-scale processes that destabilize the atmosphere. Only in the past decade has the need to represent the full convective lifecycle been recognized by the global climate modeling community, although many of the relevant features have been observed in field experiments for decades. Progress has accelerated in recent years with the aid of insights gained from cloud-resolving models and new satellite and surface remote sensing datasets. There has also been a welcome trend away from emphasis on the mean state and toward understanding of major modes of convective variability such as the Madden-Julian Oscillation and the continental diurnal cycle. On one end of the lifecycle, the need to capture the gradual transition from shallow to congestus to deep convection has renewed interest in understanding the process of entrainment and the previously underappreciated sensitivity of convection to the humidity of the free troposphere. On the other end, the tendency for convection to organize on the mesoscale in favorable humidity and shear conditions is only now beginning to receive attention in the parameterization community. Approaches to representing downdraft cold pools, which stimulate further convection and trigger organization, are now being implemented in GCMs. The subsequent evolution from convective cells to organized clusters with stratiform precipitation, which shifts the heating profile upward, extends the lifetime of convective systems, and can change the sign of convective momentum transport, remains a challenge, especially as model resolution increases.

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

PubMed Central

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

2017-01-01

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

Spatial variation and low diversity in the major histocompatibility complex in walrus (Odobenus rosmarus)

USGS Publications Warehouse

Sonsthagen, Sarah A.; Fales, Krystal R.; Jay, Chadwick V.; Sage, George K.; Talbot, Sandra L.

2014-01-01

Increased global temperature and associated changes to Arctic habitats will likely result in the northward advance of species, including an influx of pathogens novel to the Arctic. How species respond to these immunological challenges will depend in part on the adaptive potential of their immune response system. We compared levels of genetic diversity at a gene associated with adaptive immune response [Class II major histocompatibility complex (MHC), DQB exon 2] between populations of walrus (Odobenus rosmarus), a sea ice-dependent Arctic species. Walrus was represented by only five MHC DQB alleles, with frequency differences observed between Pacific and Atlantic populations. MHC DQB alleles appear to be under balancing selection, and most (80 %; n = 4/5) of the alleles were observed in walruses from both oceans, suggesting broad scale differences in the frequency of exposure and diversity of pathogens may be influencing levels of heterozygosity at DQB in walruses. Limited genetic diversity at MHC, however, suggests that walrus may have a reduced capacity to respond to novel immunological challenges associated with shifts in ecological communities and environmental stressors predicted for changing climates. This is particularly pertinent for walrus, since reductions in summer sea ice may facilitate both northward expansion of marine species and associated pathogens from more temperate regions, and exchange of marine mammals and associated pathogens through the recently opened Northwest Passage between the Atlantic and Pacific Oceans in the Canadian high Arctic.

Primordial prevention of cardiovascular disease among African-Americans: a social epidemiological perspective.

PubMed

James, S A

1999-12-01

The primordial prevention of cardiovascular disease (CVD) among African-Americans represents a formidable challenge for public health. This paper discusses the nature of this challenge, highlighting the role that economic and cultural factors play in shaping the distributions of major CVD risk factors among African-Americans. The paper concludes with specific suggestions for research. Data from recent national health surveys on black/white differences in major CVD risk factors like hypertension, obesity, cholesterol, cigarette smoking, and physical inactivity were reviewed for the purpose of identifying promising avenues for primordial prevention research among African-Americans. Cigarette smoking has a delayed onset among African-Americans compared to whites. Black/white differences in "vigorous" leisure-time physical activity (e.g., social dancing and team sports) are not apparent until around age 40. These findings have relevance for primordial prevention work in black communities since they suggest the existence of broad-based, health-relevant cultural norms which could support primordial prevention programs, such as regular physical activity, across the life cycle. CVD primordial prevention programs among African-Americans must be grounded in an understanding of how cultural values as well as economic conditions shape CVD risk factor distributions in this population. Ultimate success will depend on the strength of the partnerships that public health researchers, primary care providers, and community residents are able to build.

Practical lessons for bringing policy-makers on board in sexual and reproductive health research.

PubMed

Guieu, Aurore; Zhang, Wei-Hong; Lafort, Yves; Decat, Peter; De Meyer, Sara; Wang, Shuchen; Kerstens, Birgit; Duysburgh, Els

2016-11-11

The need to translate research into policy, i.e. making research findings a driving force in agenda-setting and policy change, is increasingly acknowledged. However, little is known about translation mechanisms in the field of sexual and reproductive health (SRH) outside North American or European contexts. This paper seeks to give an overview of the existing knowledge on this topic as well as to document practical challenges and remedies from the perspectives of researchers involved in four SRH research consortium projects in Latin America, sub-Saharan Africa, China and India. A literature review and relevant project documents were used to develop an interview guide through which researchers could reflect on their experiences in engaging with policy-makers, and particularly on the obstacles met and the strategies deployed by the four project consortia to circumvent them. Our findings confirm current recommendations on an early and steady involvement of policy-makers, however they also suggest that local barriers between researchers and policy-making spheres and individuals can represent major hindrances to the realization of translation objectives. Although many of the challenges might be common to different contexts, creating locally-adapted responses is deemed key to overcome them. Researchers' experiences also indicate that - although inevitable - recognizing and addressing these challenges is a difficult, time- and energy-consuming process for all partners involved. Despite a lack of existing knowledge on translation efforts in SRH research outside North American or European contexts, and more particularly in low and middle-income countries, it is clear that existing pressure on health and policy systems in these settings further complicates them. This article brings together literature findings and researchers' own experiences in translating research results into policy and highlights the major challenges research conducted on sexual and reproductive health outside North American or European contexts can meet. Future SRH projects should be particularly attentive to these potential obstacles in order to tailor appropriate and consistent strategies within their existing resources.

A national survey to define a new core curriculum to prepare physicians for managed care practice.

PubMed

Meyer, G S; Potter, A; Gary, N

1997-08-01

All levels of medical education will require modification to address the challenges in health care practice brought about by managed care. Because preparation for practice in a managed care environment has received insufficient attention, and because the need for change is so great, in 1995 the authors sought information from a variety of sources to serve as a basis for identifying the core curricular components and the staging of these components in the medical education process. This research effort consisted of a survey of 125 U.S. medical school curriculum deans (or equivalent school representatives); four focus groups of managed care practitioners, administrators, educators, and residents; and a survey of a national sample of physicians and medical directors. Findings indicate that almost all the 91 responding school representatives recognized the importance of revising their curricula to meet the managed care challenge and that the majority either had or were developing programs to train students for practice in managed care environments. The focus groups identified a core set of competencies for managed care practice, although numbers differed on whether the classroom or a managed care setting was the best place to teach the components of a new curriculum. Although medical directors and staff physicians differed with respect to the relative levels of importance of these competencies, the findings suggest that before medical school, training should focus on communication and interpersonal skills, information systems, and customer relations; during medical school, on clinical epidemiology, quality assurance, risk management, and decision analysis; during residency, on utilization management, managed care essentials, and multidisciplinary team building; and after residency, on a review of customer relations, communication skills, and utilization management. The authors conclude that a core curriculum and its sequencing can be identified, that the majority of curricular components exist but in s some cases needed to be modified to more clearly relate to managed care practice, and that their findings may provide a useful starting point for making decisions about curricular reform.

Development and Validation of a New Air Carrier Block Time Prediction Model and Methodology

NASA Astrophysics Data System (ADS)

Litvay, Robyn Olson

Commercial airline operations rely on predicted block times as the foundation for critical, successive decisions that include fuel purchasing, crew scheduling, and airport facility usage planning. Small inaccuracies in the predicted block times have the potential to result in huge financial losses, and, with profit margins for airline operations currently almost nonexistent, potentially negate any possible profit. Although optimization techniques have resulted in many models targeting airline operations, the challenge of accurately predicting and quantifying variables months in advance remains elusive. The objective of this work is the development of an airline block time prediction model and methodology that is practical, easily implemented, and easily updated. Research was accomplished, and actual U.S., domestic, flight data from a major airline was utilized, to develop a model to predict airline block times with increased accuracy and smaller variance in the actual times from the predicted times. This reduction in variance represents tens of millions of dollars (U.S.) per year in operational cost savings for an individual airline. A new methodology for block time prediction is constructed using a regression model as the base, as it has both deterministic and probabilistic components, and historic block time distributions. The estimation of the block times for commercial, domestic, airline operations requires a probabilistic, general model that can be easily customized for a specific airline’s network. As individual block times vary by season, by day, and by time of day, the challenge is to make general, long-term estimations representing the average, actual block times while minimizing the variation. Predictions of block times for the third quarter months of July and August of 2011 were calculated using this new model. The resulting, actual block times were obtained from the Research and Innovative Technology Administration, Bureau of Transportation Statistics (Airline On-time Performance Data, 2008-2011) for comparison and analysis. Future block times are shown to be predicted with greater accuracy, without exception and network-wide, for a major, U.S., domestic airline.

Management of delayed major visceral arterial bleeding after pancreatic surgery

PubMed Central

Schäfer, Markus; Heinrich, Stefan; Pfammatter, Thomas; Clavien, Pierre-Alain

2011-01-01

Objectives Postoperative bleeding represents a life-threatening complication after pancreatic surgery. Recent developments in interventional radiology have challenged the role of surgery in bleeding control. This study aimed to assess the management of major haemorrhagic complications after pancreatic surgery at a tertiary referral centre. Methods Between August 1998 and June 2009, 18 patients with major bleeding after pancreatic surgery were admitted to the University Hospital of Zurich, Zurich, Switzerland. We retrospectively analysed their medical charts, focusing on diagnosis, therapy and outcome. Results Major arterial bleeding occurred after a median postoperative interval of 21.5 days (range: 9–259 days). Seventeen patients demonstrated various symptoms, such as repeated upper gastrointestinal bleeding or haemorrhagic shock. Diagnosis was usually made by contrast-enhanced computed tomography (CT). Leakage of the pancreaticojejunostomy caused the formation of a pseudoaneurysm in 78% of patients. Haemostasis was achieved in 10 patients by interventional radiology. Two patients died of massive re-bleeding. Six patients underwent primary emergency surgery, which five did not survive. Conclusions Delayed bleeding after pancreatic surgery is suspicious for a pseudoaneurysm. Contrast-enhanced CT followed by early angiography provides accurate diagnosis and treatment. Interventional radiological treatment should be preferred over primary surgery because it is currently the most life-saving approach. PMID:21241431

Perspectives of unlicensed assistive personnel on career development.

PubMed

Akaragian, Salpy; Crooks, Heidi; Pieters, Huibrie C

2013-09-01

An equivalency program, Method 3, is a viable but underused option for unlicensed assistive personnel (UAP) who pursue licensure. This study describes the perceptions of UAP on opportunities for career development. Eighteen UAP participated in three focus groups. Thematic analysis was conducted with verbatim transcription. Three major themes represented the lively discussions that occurred: core driving forces, processes of career development, and anticipated and desirable outcomes. Various subthemes described these major themes. Method 3 provides a realistic approach to help UAP persevere with career development. Collaboration with management and peers, encouragement, and effective communication contributed to the success of participants, despite obstacles and challenges. Camaraderie and flexible scheduling were critical elements in participants' pursuit of first licensure. Taking small steps was described as an effective approach for UAP to persevere with career development. Support for informal career development is essential. Nursing leaders should consider an equivalency approach to accommodate individual preferences and learning needs for career development. Copyright 2013, SLACK Incorporated.

Care for Canada's frail elderly population: Fragmentation or integration?

PubMed Central

Bergman, H; Béland, F; Lebel, P; Contandriopoulos, A P; Tousignant, P; Brunelle, Y; Kaufman, T; Leibovich, E; Rodriguez, R; Clarfield, M

1997-01-01

Budget constraints, technological advances and a growing elderly population have resulted in major reforms in health care systems across Canada. This has led to fewer and smaller acute care hospitals and increasing pressure on the primary care and continuing care networks. The present system of care for the frail elderly, who are particularly vulnerable, is characterized by fragmentation of services, negative incentives and the absence of accountability. This is turn leads to the inappropriate and costly use of health and social services, particularly in acute care hospitals and long-term care institutions. Canada needs to develop a publicly managed community-based system of primary care to provide integrated care for the frail elderly. The authors describe such a model, which would have clinical and financial responsibility for the full range of health and social services required by this population. This model would represent a major challenge and change for the existing system. Demonstration projects are needed to evaluate its cost-effectiveness and address issues raised by its introduction. PMID:9347783

Frost Monitoring and Forecasting Using MODIS Land Surface Temperature Data and a Numerical Weather Prediction Model Forecasts for Eastern Africa

NASA Technical Reports Server (NTRS)

Kabuchanga, Eric; Flores, Africa; Malaso, Susan; Mungai, John; Sakwa, Vincent; Shaka, Ayub; Limaye, Ashutosh

2014-01-01

Frost is a major challenge across Eastern Africa, severely impacting agricultural farms. Frost damages have wide ranging economic implications on tea and coffee farms, which represent a major economic sector. Early monitoring and forecasting will enable farmers to take preventive actions to minimize the losses. Although clearly important, timely information on when to protect crops from freezing is relatively limited. MODIS Land Surface Temperature (LST) data, derived from NASA's Terra and Aqua satellites, and 72-hr weather forecasts from the Kenya Meteorological Service's operational Weather Research Forecast model are enabling the Regional Center for Mapping of Resources for Development (RCMRD) and the Tea Research Foundation of Kenya to provide timely information to farmers in the region. This presentation will highlight an ongoing collaboration among the Kenya Meteorological Service, RCMRD, and the Tea Research Foundation of Kenya to identify frost events and provide farmers with potential frost forecasts in Eastern Africa.

Operating a production pilot factory serving several scientific domains

NASA Astrophysics Data System (ADS)

Sfiligoi, I.; Würthwein, F.; Andrews, W.; Dost, J. M.; MacNeill, I.; McCrea, A.; Sheripon, E.; Murphy, C. W.

2011-12-01

Pilot infrastructures are becoming prominent players in the Grid environment. One of the major advantages is represented by the reduced effort required by the user communities (also known as Virtual Organizations or VOs) due to the outsourcing of the Grid interfacing services, i.e. the pilot factory, to Grid experts. One such pilot factory, based on the glideinWMS pilot infrastructure, is being operated by the Open Science Grid at University of California San Diego (UCSD). This pilot factory is serving multiple VOs from several scientific domains. Currently the three major clients are the analysis operations of the HEP experiment CMS, the community VO HCC, which serves mostly math, biology and computer science users, and the structural biology VO NEBioGrid. The UCSD glidein factory allows the served VOs to use Grid resources distributed over 150 sites in North and South America, in Europe, and in Asia. This paper presents the steps taken to create a production quality pilot factory, together with the challenges encountered along the road.

Transdermal Delivery of siRNA through Microneedle Array

NASA Astrophysics Data System (ADS)

Deng, Yan; Chen, Jiao; Zhao, Yi; Yan, Xiaohui; Zhang, Li; Choy, Kwongwai; Hu, Jun; Sant, Himanshu J.; Gale, Bruce K.; Tang, Tao

2016-02-01

Successful development of siRNA therapies has significant potential for the treatment of skin conditions (alopecia, allergic skin diseases, hyperpigmentation, psoriasis, skin cancer, pachyonychia congenital) caused by aberrant gene expression. Although hypodermic needles can be used to effectively deliver siRNA through the stratum corneum, the major challenge is that this approach is painful and the effects are restricted to the injection site. Microneedle arrays may represent a better way to deliver siRNAs across the stratum corneum. In this study, we evaluated for the first time the ability of the solid silicon microneedle array for punching holes to deliver cholesterol-modified housekeeping gene (Gapdh) siRNA to the mouse ear skin. Treating the ear with microneedles showed permeation of siRNA in the skin and could reduce Gapdh gene expression up to 66% in the skin without accumulation in the major organs. The results showed that microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively.

Rise of an alternative majority against opinion leaders

NASA Astrophysics Data System (ADS)

Tucci, K.; González-Avella, J. C.; Cosenza, M. G.

2016-03-01

We investigate the role of opinion leaders or influentials in the collective behavior of a social system. Opinion leaders are characterized by their unidirectional influence on other agents. We employ a model based on Axelrod's dynamics for cultural interaction among social agents that allows for non-interacting states. We find three collective phases in the space of parameters of the system, given by the fraction of opinion leaders and a quantity representing the number of available states: one ordered phase having the state imposed by the leaders; another nontrivial ordered phase consisting of a majority group in a state orthogonal or alternative to that of the opinion leaders, and a disordered phase, where many small groups coexist. We show that the spontaneous rise of an alternative group in the presence of opinion leaders depends on the existence of a minimum number of long-range connections in the underlying network. This phenomenon challenges the common idea that influentials are fundamental to propagation processes in society, such as the formation of public opinion.

Interphase FISH for BCR-ABL1 rearrangement on neutrophils: A decisive tool to discriminate a lymphoid blast crisis of chronic myeloid leukemia from a de novo BCR-ABL1 positive acute lymphoblastic leukemia.

PubMed

Balducci, Estelle; Loosveld, Marie; Rahal, Ilhem; Boudjarane, John; Alazard, Emilie; Missirian, Chantal; Lafage-Pochitaloff, Marina; Michel, Gérard; Zattara, Hélène

2018-02-01

Discrimination between lymphoid blast crisis of chronic myeloid leukemia (CML) and de novo BCR-ABL1 positive acute lymphoblastic leukemia (ALL) represents a diagnostic challenge because this distinction has a major incidence on the management of patients. Here, we report an uncommon pediatric case of ALL with cryptic ins(22;9)(q11;q34q34) and p190-type BCR-ABL1 transcript. We performed interphase fluorescence in situ hybridization (FISH) for BCR-ABL1 rearrangement on blood neutrophils, which was positive consistent with the diagnosis of lymphoid blast crisis of CML. This case illustrates the major interest of interphase FISH for BCR-ABL1 rearrangement on blood neutrophils as a decisive method to discriminate a lymphoid blast crisis of CML from a de novo BCR-ABL1 positive ALL. Copyright © 2017 John Wiley & Sons, Ltd.

Implementing a regional oncology information system: approach and lessons learned.

PubMed

Evans, W K; Ashbury, F D; Hogue, G L; Smith, A; Pun, J

2014-10-01

Paper-based medical record systems are known to have major problems of inaccuracy, incomplete data, poor accessibility, and challenges to patient confidentiality. They are also an inefficient mechanism of record-sharing for interdisciplinary patient assessment and management, and represent a major problem for keeping current and monitoring quality control to facilitate improvement. To address those concerns, national, regional, and local health care authorities have increased the pressure on oncology practices to upgrade from paper-based systems to electronic health records. Here, we describe and discuss the challenges to implementing a region-wide oncology information system across four independent health care organizations, and we describe the lessons learned from the initial phases that are now being applied in subsequent activities of this complex project. The need for change must be shared across centres to increase buy-in, adoption, and implementation. It is essential to establish physician leadership, commitment, and engagement in the process. Work processes had to be revised to optimize use of the new system. Culture change must be included in the change management strategy. Furthermore, training and resource requirements must be thoroughly planned, implemented, monitored, and modified as required for effective adoption of new work processes and technology. Interfaces must be established with multiple existing electronic systems across the region to ensure appropriate patient flow. Periodic assessment of the existing project structure is necessary, and adjustments are often required to ensure that the project meets its objectives. The implementation of region-wide oncology information systems across different health practice locations has many challenges. Leadership is essential. A strong, collaborative information-sharing strategy across the region and with the supplier is essential to identify, discuss, and resolve implementation problems. A structure that supports project management and accountability contributes to success.

Temporal dynamics of the HPA axis linked to exploratory behavior in a wild European songbird (Parus major).

PubMed

Baugh, Alexander T; Davidson, Sarah C; Hau, Michaela; van Oers, Kees

2017-09-01

Variation in the reactivity of the endocrine stress axis is thought to underlie aspects of persistent individual differences in behavior (i.e. animal personality). Previous studies, however, have focused largely on estimating baseline or peak levels of glucocorticoids (CORT), often in captive animals. In contrast, the temporal dynamics of the HPA axis-how quickly it turns on and off, for example-may better indicate how an individual copes with stressors. Moreover, these HPA components might be correlated, thereby representing endocrine suites. Using wild-caught great tits (Parus major) we tested birds for exploratory behavior using a standardized novel environment assay that serves as a validated proxy for personality. We then re-captured a subset of these birds (n=85) and characterized four components of HPA physiology: baseline, endogenous stress response, a dexamethasone (DEX) challenge to estimate the strength of negative feedback, and an adrenocorticotropic hormone (ACTH) challenge to estimate adrenal capacity. We predicted that these four HPA responses would be positively correlated and that less exploratory birds would have a more rapid onset of the stress response (a CORT elevation during the baseline bleed) and weaker negative feedback (higher CORT after DEX). We found support for the first two predictions but not the third. All four components were positively correlated with each other and less exploratory birds exhibited an elevation in CORT during the baseline bleed (<3min from capture). Less exploratory birds, however, did not exhibit weaker negative feedback following the DEX challenge, but did exhibit weaker adrenal capacity. Together, our findings provide partial support for the hypothesis that the temporal reactivity of the HPA axis is linked with consistent individual differences in behavior, with more cautious (slower exploring) individuals exhibiting a faster CORT response. Copyright © 2017 Elsevier Inc. All rights reserved.

Crown-level tree species classification from AISA hyperspectral imagery using an innovative pixel-weighting approach

NASA Astrophysics Data System (ADS)

Liu, Haijian; Wu, Changshan

2018-06-01

Crown-level tree species classification is a challenging task due to the spectral similarity among different tree species. Shadow, underlying objects, and other materials within a crown may decrease the purity of extracted crown spectra and further reduce classification accuracy. To address this problem, an innovative pixel-weighting approach was developed for tree species classification at the crown level. The method utilized high density discrete LiDAR data for individual tree delineation and Airborne Imaging Spectrometer for Applications (AISA) hyperspectral imagery for pure crown-scale spectra extraction. Specifically, three steps were included: 1) individual tree identification using LiDAR data, 2) pixel-weighted representative crown spectra calculation using hyperspectral imagery, with which pixel-based illuminated-leaf fractions estimated using a linear spectral mixture analysis (LSMA) were employed as weighted factors, and 3) representative spectra based tree species classification was performed through applying a support vector machine (SVM) approach. Analysis of results suggests that the developed pixel-weighting approach (OA = 82.12%, Kc = 0.74) performed better than treetop-based (OA = 70.86%, Kc = 0.58) and pixel-majority methods (OA = 72.26, Kc = 0.62) in terms of classification accuracy. McNemar tests indicated the differences in accuracy between pixel-weighting and treetop-based approaches as well as that between pixel-weighting and pixel-majority approaches were statistically significant.

High-speed inlet research program and supporting analyses

NASA Technical Reports Server (NTRS)

Coltrin, Robert E.

1987-01-01

A Mach 5 cruise aircraft was studied in a joint program effort. The propulsion system chosen for this aircraft was an over-under turbojet/ramjet system. The ramjet portion of the inlet is to be tested in NASA Lewis' 10 x 10 SWT. Goals of the test program are to obtain performance data and bleed requirements, and also to obtain analysis code validation data. Supporting analysis of the inlet using a three-dimensional Navier-Stokes code (PEPSIS) indicates that sidewall shock/boundary layer interactions cause large separated regions in the corners underneath the cowl. Such separations generally lead to inlet unstart, and are thus a major concern. As a result of the analysis, additional bleed regions were added to the inlet model sidewalls and cowl to control separations in the corners. A two-dimensional analysis incorporating bleed on the ramp is also presented. Supporting experiments for the Mach 5 programs were conducted in the Lewis' 1 x 1 SWT. A small-scale model representing the inlet geometry up to the ramp shoulder and cowl lip was tested to verify the accelerator plate test technique and to obtain data on flow migration in the ramp and sidewall boundary layers. Another study explored several ramp bleed configurations to control boundary layer separations in that region. Design of a two-dimensional Mach 5 cruise inlet represents several major challenges including multimode operation and dual flow, high temperatures, and three-dimensional airflow effects.

Epilepsy services in Saudi Arabia

PubMed Central

Alfayez, Saud M.; Aljafen, Bandar N.

2016-01-01

Objective: To assess the epilepsy services and identify the challenges in hospitals without epilepsy monitoring units (EMUs). In addition, comparisons between governmental and private sectors, as well as between regions, are to be performed. Methods: A cross-sectional study conducted using an online questionnaire distributed to the secondary and tertiary hospitals without EMUs throughout the Kingdom of Saudi Arabia (KSA). The study was conducted from September 2013 to September 2015 and regular updates from all respondents were constantly made. Items in the questionnaire included the region of the institution, the number of pediatric and adult neurologists and neurosurgeons along with their subspecialties, the number of beds in the Neurology Department, whether they provide educational services and have epilepsy clinics and if they refer patients to an EMU or intend to establish one in the future. Results: Forty-three institutions throughout the Kingdom responded, representing a response rate of 54%. The majority of hospitals (58.1%) had no adult epileptologists. A complete lack of pediatric epileptologists was observed in 72.1% of hospitals. Around 39.5% were utilizing beds from internal medicine. Hospitals with an epilepsy clinic represented 34.9% across all regions and sectors. Hospitals with no intention of establishing an EMU represented 53.5%. Hospitals that did not refer their epileptic patients to an EMU represented 30.2%. Conclusions: Epilepsy services in KSA hospitals without EMUs are underdeveloped. PMID:27744461

Prevalence of mental, neurological, and substance use disorders in China and India: a systematic analysis.

PubMed

Baxter, Amanda J; Charlson, Fiona J; Cheng, Hui G; Shidhaye, Rahul; Ferrari, Alize J; Whiteford, Harvey A

2016-09-01

Population-representative prevalence data for mental, neurological, and substance use disorders are essential for evidence-based decision making. As a background to the China-India Mental Health Alliance Series, we aim to examine the availability of data and report prevalence for the most common mental, neurological, and substance use disorders in China and India from the Global Burden of Disease study 2013 (GBD 2013). In this systematic analysis, data sources were identified from GBD 2013 for the prevalence of mental, neurological, and substance use disorders in China and India published up to Dec 31, 2013. We calculated the proportion of the population represented by the data with the adjusted population coverage (APC) method adjusting for age, sex, and population size. We developed prevalence models with DisMod-MR 2.0, a Bayesian meta-regression instrument used to pool population-representative epidemiological data as part of GBD 2013. We report estimates and 95% uncertainly intervals (95% UI) for 15 mental, neurological, and substance use disorders for China and India in 1990 and 2013, and benchmark these against those for other BRICS countries (Brazil, Russia, and South Africa) in 2013. Few population-representative data were found for the disorders, with an average coverage of 15% of the population of the Chinese mainland and 1% of the population of India. For men in both China and India, major depressive disorder, anxiety disorders, and alcohol dependence were the most common mental, neurological, and substance use disorders. Prevalence of major depressive disorder was 2·2% (95% UI 1·5-2·8) in Chinese men and 3·5% (2·4-4·6) in Indian men; prevalence of anxiety disorders was 2·0% (1·1-3·2) and 1·9% (1·2-2·3), respectively. For women, anxiety disorders, major depressive disorder, and dysthymia were the most common. Prevalence of major depressive disorder was 3·3% (2·3-4·1) in Chinese women and 4·7% (95% UI 3·3-6·2) in Indian women; prevalence of anxiety disorders was 3·3% (1·6-5·3) and 4·1% (3·3-5·0), respectively. Schizophrenia was more prevalent in China (0·5%, 95% UI 0·4-0·5) than in India (0·2%; 0·2-0·2). More data for mental, neurological, and substance use disorders are needed for India and China but the large population and geographic scale of these countries present challenges to population-representative data collection. China-India Mental Health Alliance, China Medical Board. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early Potent Protection against Heterologous SIVsmE660 Challenge Following Live Attenuated SIV Vaccination in Mauritian Cynomolgus Macaques

PubMed Central

Berry, Neil; Ham, Claire; Mee, Edward T.; Rose, Nicola J.; Mattiuzzo, Giada; Jenkins, Adrian; Page, Mark; Elsley, William; Robinson, Mark; Smith, Deborah; Ferguson, Deborah; Towers, Greg; Almond, Neil; Stebbings, Richard

2011-01-01

Background Live attenuated simian immunodeficiency virus (SIV) vaccines represent the most effective means of vaccinating macaques against pathogenic SIV challenge. However, thus far, protection has been demonstrated to be more effective against homologous than heterologous strains. Immune correlates of vaccine-induced protection have also been difficult to identify, particularly those measurable in the peripheral circulation. Methodology/Principal Findings Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus macaques (MCM) against heterologous virus challenge with the pathogenic, uncloned SIVsmE660 viral stock following vaccination with live attenuated SIVmac251/C8. MCM provided a characterised host genetic background with limited Major Histocompatibility Complex (MHC) and TRIM5α allelic diversity. Early protection, observed as soon as 3 weeks post-vaccination, was comparable to that of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in breakthrough cases where simultaneous identification of vaccine and challenge viruses by virus-specific PCR was indicative of active co-infection. Persistence of the vaccine virus in a range of lymphoid tissues was typified by a consistent level of SIV RNA positive cells in protected vaccinates. However, no association between MHC class I /II haplotype or TRIM5α polymorphism and study outcome was identified. Conclusion/Significance This SIV vaccine study, conducted in MHC-characterised MCM, demonstrated potent protection against the pathogenic, heterologous SIVsmE660 challenge stock after only 3 weeks vaccination. This level of protection against this viral stock by intravenous challenge has not been hitherto observed. The mechanism(s) of protection by vaccination with live attenuated SIV must account for the heterologous and early protection data described in this study, including those which relate to the innate immune system. PMID:21853072

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

Universalizing Nine-Year Compulsory Education For Poverty Reduction in Rural China

NASA Astrophysics Data System (ADS)

Zhang, Tiedao; Minxia, Zhao

2006-05-01

Lack of access to basic education leads to diminished individual and national capabilities, therewith furthering cycles of poverty. An equitable education system meeting basic learning needs represents not only a human right, but also a means for reducing poverty, promoting productivity, and sustaining development. The Government of China - the most populous developing nation, the majority of whose citizens live in rural areas - has been committed to universalizing nine-year compulsory education among school-aged children and eliminating illiteracy among youths and adults aged 15-45. This study examines lessons learned from China's efforts in these areas. It also reports on current challenges and trends in a new national initiative for achieving high-quality universal basic education by the year 2007.

Growth versus immunity--a redirection of the cell cycle?

PubMed

Eichmann, Ruth; Schäfer, Patrick

2015-08-01

Diseases caused by plant pathogens significantly reduce growth and yield in agricultural crop production. Raising immunity in crops is therefore a major aim in breeding programs. However, efforts to enhance immunity are challenged by the occurrence of growth inhibition triggered by immunity that can be as detrimental as diseases. In this review, we will propose molecular models to explain the inhibitory growth-immunity crosstalk. We will briefly discuss why the resource reallocation model might not represent the driving force for the observed growth-immunity trade-offs. We suggest a model in which immunity redirects and initiates hormone signalling activities that can impair plant growth by antagonising cell cycle regulation and meristem activities. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Demand Response and Energy Storage Integration Study

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

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

2016-03-01

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

Database usage and performance for the Fermilab Run II experiments

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

Bonham, D.; Box, D.; Gallas, E.

2004-12-01

The Run II experiments at Fermilab, CDF and D0, have extensive database needs covering many areas of their online and offline operations. Delivering data to users and processing farms worldwide has represented major challenges to both experiments. The range of applications employing databases includes, calibration (conditions), trigger information, run configuration, run quality, luminosity, data management, and others. Oracle is the primary database product being used for these applications at Fermilab and some of its advanced features have been employed, such as table partitioning and replication. There is also experience with open source database products such as MySQL for secondary databasesmore » used, for example, in monitoring. Tools employed for monitoring the operation and diagnosing problems are also described.« less

Core–Shell Nanoparticle Coating as an Interfacial Layer for Dendrite-Free Lithium Metal Anodes

DOE PAGES

Liu, Wei; Li, Weiyang; Zhuo, Denys; ...

2017-02-08

Lithium metal based batteries represent a major challenge and opportunity in enabling a variety of devices requiring high-energy-density storage. However, dendritic lithium growth has limited the practical application of lithium metal anodes. Here we report a nanoporous, flexible and electrochemically stable coating of silica@poly(methyl methacrylate) (SiO 2@PMMA) core–shell nanospheres as an interfacial layer on lithium metal anode. This interfacial layer is capable of inhibiting Li dendrite growth while sustaining ionic flux through it, which is attributed to the nanoscaled pores formed among the nanospheres. Lastly, enhanced Coulombic efficiencies during lithium charge/discharge cycles have been achieved at various current densities andmore » areal capacities.« less

Core–Shell Nanoparticle Coating as an Interfacial Layer for Dendrite-Free Lithium Metal Anodes

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

Liu, Wei; Li, Weiyang; Zhuo, Denys

Lithium metal based batteries represent a major challenge and opportunity in enabling a variety of devices requiring high-energy-density storage. However, dendritic lithium growth has limited the practical application of lithium metal anodes. Here we report a nanoporous, flexible and electrochemically stable coating of silica@poly(methyl methacrylate) (SiO 2@PMMA) core–shell nanospheres as an interfacial layer on lithium metal anode. This interfacial layer is capable of inhibiting Li dendrite growth while sustaining ionic flux through it, which is attributed to the nanoscaled pores formed among the nanospheres. Lastly, enhanced Coulombic efficiencies during lithium charge/discharge cycles have been achieved at various current densities andmore » areal capacities.« less

Application of Game Theory Approaches in Routing Protocols for Wireless Networks

NASA Astrophysics Data System (ADS)

Javidi, Mohammad M.; Aliahmadipour, Laya

2011-09-01

An important and essential issue for wireless networks is routing protocol design that is a major technical challenge due to the function of the network. Game theory is a powerful mathematical tool that analyzes the strategic interactions among multiple decision makers and the results of researches show that applied game theory in routing protocol lead to improvement the network performance through reduce overhead and motivates selfish nodes to collaborate in the network. This paper presents a review and comparison for typical representatives of routing protocols designed that applied game theory approaches for various wireless networks such as ad hoc networks, mobile ad hoc networks and sensor networks that all of them lead to improve the network performance.

From the connectome to the synaptome: an epic love story.

PubMed

DeFelipe, Javier

2010-11-26

A major challenge in neuroscience is to decipher the structural layout of the brain. The term "connectome" has recently been proposed to refer to the highly organized connection matrix of the human brain. However, defining how information flows through such a complex system represents so difficult a task that it seems unlikely it could be achieved in the near future or, for the most pessimistic, perhaps ever. Circuit diagrams of the nervous system can be considered at different levels, although they are surely impossible to complete at the synaptic level. Nevertheless, advances in our capacity to marry macro- and microscopic data may help establish a realistic statistical model that could describe connectivity at the ultrastructural level, the "synaptome," giving us cause for optimism.

Advances in native high-performance liquid chromatography and intact mass spectrometry for the characterization of biopharmaceutical products.

PubMed

Tassi, Marco; De Vos, Jelle; Chatterjee, Sneha; Sobott, Frank; Bones, Jonathan; Eeltink, Sebastiaan

2018-01-01

The characterization of biotherapeutics represents a major analytical challenge. This review discusses the current state-of-the-art in analytical technologies to profile biopharma products under native conditions, i.e., the protein three dimensional conformation is maintained during liquid chromatographic analysis. Native liquid-chromatographic modes that are discussed include aqueous size-exclusion chromatography, hydrophobic interaction chromatography, and ion-exchange chromatography. Infusion conditions and the possibilities and limitations to hyphenate native liquid chromatography to mass spectrometry are discussed. Furthermore, the applicability of native liquid-chromatography methods and intact mass spectrometry analysis for the characterization of monoclonal antibodies and antibody-drug conjugates is discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Demand Response and Energy Storage Integration Study

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

Ma, Ookie; Cheung, Kerry

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

Carbon Nanotubes in Biomedical Applications: Factors, Mechanisms, and Remedies of Toxicity.

PubMed

Alshehri, Reem; Ilyas, Asad Muhammad; Hasan, Anwarul; Arnaout, Adnan; Ahmed, Farid; Memic, Adnan

2016-09-22

Carbon nanotubes (CNTs) represent one of the most studied allotropes of carbon. The unique physicochemical properties of CNTs make them among prime candidates for numerous applications in biomedical fields including drug delivery, gene therapy, biosensors, and tissue engineering applications. However, toxicity of CNTs has been a major concern for their use in biomedical applications. In this review, we present an overview of carbon nanotubes in biomedical applications; we particularly focus on various factors and mechanisms affecting their toxicity. We have discussed various parameters including the size, length, agglomeration, and impurities of CNTs that may cause oxidative stress, which is often the main mechanism of CNTs' toxicity. Other toxic pathways are also examined, and possible ways to overcome these challenges have been discussed.

Bacterial Hydrodynamics

NASA Astrophysics Data System (ADS)

Lauga, Eric

2016-01-01

Bacteria predate plants and animals by billions of years. Today, they are the world's smallest cells, yet they represent the bulk of the world's biomass and the main reservoir of nutrients for higher organisms. Most bacteria can move on their own, and the majority of motile bacteria are able to swim in viscous fluids using slender helical appendages called flagella. Low-Reynolds number hydrodynamics is at the heart of the ability of flagella to generate propulsion at the micrometer scale. In fact, fluid dynamic forces impact many aspects of bacteriology, ranging from the ability of cells to reorient and search their surroundings to their interactions within mechanically and chemically complex environments. Using hydrodynamics as an organizing framework, I review the biomechanics of bacterial motility and look ahead to future challenges.

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

DTIC Science & Technology

2008-12-01

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

Perception of Iranian Middle-Aged Women Regarding Moral Health Concept: A Content Analysis

PubMed Central

Salsali, Mahvash; Rezaee, Nasrin; Seyedfatemi, Naimeh; Rahnavard, Zahra

2015-01-01

Introduction: The present study aimed at exploring and describing the perception of moral health from middle-aged women standpoints. Women’s decisive role in family is undeniable. In the family which is built upon tradition, faith and ethics, this is women’s principle which is represented in the moral health of the individual and the society, deals with the nature of the vice and virtue. This study attempted to identify the perception of Iranian middle-aged women about the concept of moral health. Method: The present study completed through a content analysis method. Twenty two middle-aged women were recruited through purposive sampling. Data were granted by face to face, semi-structured interview. Result: Our major categories are devotion, preserving moral values and moral challenges. Devotion category includes subcategories such as prioritizing the health of family members and trying to save marriage. Preserving moral values category includes subcategories such as respecting values and consolidating beliefs over time. Moral challenges category consists of individual and familial challenges subcategories. Conclusion: Moral health is of high importance which affects various dimensions of individual, social and familial life. The findings of the present study presented new dimensions of middle-aged women’s health regarding moral health which can finally have different consequences on familial and social moral health. PMID:25948455

Perception of Iranian middle-aged women regarding moral health concept: a content analysis.

PubMed

Salsali, Mahvash; Rezaee, Nasrin; Seyedfatemi, Naimeh; Rahnavard, Zahra

2014-11-30

The present study aimed at exploring and describing the perception of moral health from middle-aged women standpoints. Women's decisive role in family is undeniable. In the family which is built upon tradition, faith and ethics, this is women's principle which is represented in the moral health of the individual and the society, deals with the nature of the vice and virtue. This study attempted to identify the perception of Iranian middle-aged women about the concept of moral health. The present study completed through a content analysis method. Twenty two middle-aged women were recruited through purposive sampling. Data were granted by face to face, semi-structured interview. Our major categories are devotion, preserving moral values and moral challenges. Devotion category includes subcategories such as prioritizing the health of family members and trying to save marriage. Preserving moral values category includes subcategories such as respecting values and consolidating beliefs over time. Moral challenges category consists of individual and familial challenges subcategories. Moral health is of high importance which affects various dimensions of individual, social and familial life. The findings of the present study presented new dimensions of middle-aged women's health regarding moral health which can finally have different consequences on familial and social moral health.

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

PubMed Central

Plésiat, Patrick

2015-01-01

SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps. PMID:25788514

Comorbid Normal Pressure Hydrocephalus with Parkinsonism: A Clinical Challenge and Call for Awareness.

PubMed

Cucca, A; Biagioni, M C; Sharma, K; Golomb, J; Gilbert, R M; Di Rocco, A; Fleisher, J E

2018-01-01

Idiopathic normal pressure hydrocephalus (iNPH) is the most common cause of hydrocephalus in adults. The diagnosis may be challenging, requiring collaborative efforts between different specialists. According to the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders, iNPH should be considered in the differential of any unexplained gait failure with insidious onset. Recognizing iNPH can be even more difficult in the presence of comorbid neurologic disorders. Among these, idiopathic Parkinson's disease (PD) is one of the major neurologic causes of gait dysfunction in the elderly. Both conditions have their peak prevalence between the 6th and the 7th decade. Importantly, postural instability and gait dysfunction are core clinical features in both iNPH and PD. Therefore, diagnosing iNPH where diagnostic criteria of PD have been met represents an additional clinical challenge. Here, we report a patient with parkinsonism initially consistent with PD who subsequently displayed rapidly progressive postural instability and gait dysfunction leading to the diagnosis of concomitant iNPH. In the following sections, we will review the clinical features of iNPH, as well as the overlapping and discriminating features when degenerative parkinsonism is in the differential diagnosis. Understanding and recognizing the potential for concomitant disease are critical when treating both conditions.

Inclusion and exclusion in nutrigenetics clinical research: ethical and scientific challenges.

PubMed

Hurlimann, T; Stenne, R; Menuz, V; Godard, B

2011-01-01

There are compelling reasons to ensure the participation of ethnic minorities and populations of all ages worldwide in nutrigenetics clinical research. If findings in such research are valid for some individuals, groups, or communities, and not for others, then ethical questions of justice--and not only issues of methodology and external validity--arise. This paper aims to examine inclusion in nutrigenetics clinical research and its scientific and ethical challenges. In total, 173 publications were identified through a systematic review of clinical studies in nutrigenetics published between 1998 and 2007. Data such as participants' demographics as well as eligibility criteria were extracted. There is no consistency in the way participants' origins (ancestry, ethnicity, or race) and ages are described in publications. A vast majority of the studies identified was conducted in North America and Europe and focused on 'white' participants. Our results show that pregnant women (and fetuses), minors, and the elderly (≥ 75 years old) remain underrepresented. Representativeness in nutrigenetics research is a challenging ethical and scientific issue. Yet, if nutrigenetics is to benefit whole populations and be used in public and global health agendas, fair representation as well as clear descriptions of participants in publications are crucial. Copyright © 2012 S. Karger AG, Basel.

Non-invasive systemic drug delivery through mucosal routes.

PubMed

Goyal, Amit K; Singh, Ranjit; Chauhan, Gaurav; Rath, Goutam

2018-04-24

Science of drug delivery has achieved tremendous milestones in the last few decades. Emergence of novel drug delivery techniques and the most popular nanotechnology directed the drug delivery to another level. Without any doubt, present technology holds the proficiency to approach even the intercellular targets. Between all these success auras, there lies wads of giant challenges. One such challenge is delivering the molecule directly to the blood stream. Parenteral route is considered as the most effective route for delivering active pharmaceutical substances, but is associated with major disadvantages of painful drug delivery. Modern drug delivery suggests several approaches to outstrip this painful phenomenon. In the present article, we represent a new systematic vision to understand the ability and desirability of mucosal sites to achieve painless drug delivery. Human mucosa presents supreme proximity to the blood circulation that one can even observe with naked eye. Advances in drug delivery provide numerous approaches to exploit the mucosa for systemic reach. However, the revolutionary success is still unapproachable, with an understandable reason of associated complexities and challenges. This manuscript summarizes the significance of each mucosal site, on the basis of anatomical-physiological grounds. Particular attention is given to rationalize the selection of disease and a suitable drug delivery approach for its treatment.

Implementing guideline based heart failure care in the Northern Territory: challenges and solutions.

PubMed

Iyngkaran, Pupalan; Harris, Melanie; Ilton, Marcus; Kangaharan, Nadarajan; Battersby, Malcolm; Stewart, Simon; Brown, Alex

2014-05-01

The Northern Territory of Australia is a vast area serviced by two major tertiary hospitals. It has both a unique demography and geography, which pose challenges for delivering optimal heart failure services. The prevalence of congestive heart failure continues to increase, imposing a significant burden on health infrastructure and health care costs. Specific patient groups suffer disproportionately from increased disease severity or service related issues often represented as a "health care gap". The syndrome itself is characterised by ongoing symptoms interspersed with acute decompensation requiring lifelong therapy and is rarely reversible. For the individual client the overwhelming attention to heart failure care and the impact of health care gaps can be devastating. This gap may also contribute to widening socio-economic differentials for families and communities as they seek to take on some of the care responsibilities. This review explores the challenges of heart failure best practice in the Northern Territory and the opportunities to improve on service delivery. The discussions highlighted could have implications for health service delivery throughout regional centres in Australia and health systems in other countries. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models

PubMed Central

Rivera-Hernandez, Tania; Pandey, Manisha; Henningham, Anna; Cole, Jason; Choudhury, Biswa; Cork, Amanda J.; Gillen, Christine M.; Ghaffar, Khairunnisa Abdul; West, Nicholas P.; Silvestri, Guido; Good, Michael F.; Moyle, Peter M.; Toth, Istvan; Nizet, Victor; Batzloff, Michael R.

2016-01-01

ABSTRACT Group A Streptococcus (GAS) is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i) streptolysin O (SLO), interleukin 8 (IL-8) protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP]), group A streptococcal C5a peptidase (SCPA), arginine deiminase (ADI), and trigger factor (TF); (ii) the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii) group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model. PMID:27302756

Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Coelomocytes of Sea Cucumber (Apostichopus japonicus) after Vibrio splendidus Challenge.

PubMed

Gao, Qiong; Liao, Meijie; Wang, Yingeng; Li, Bin; Zhang, Zheng; Rong, Xiaojun; Chen, Guiping; Wang, Lan

2015-07-17

Vibrio splendidus is identified as one of the major pathogenic factors for the skin ulceration syndrome in sea cucumber (Apostichopus japonicus), which has vastly limited the development of the sea cucumber culture industry. In order to screen the immune genes involving Vibrio splendidus challenge in sea cucumber and explore the molecular mechanism of this process, the related transcriptome and gene expression profiling of resistant and susceptible biotypes of sea cucumber with Vibrio splendidus challenge were collected for analysis. A total of 319,455,942 trimmed reads were obtained, which were assembled into 186,658 contigs. After that, 89,891 representative contigs (without isoform) were clustered. The analysis of the gene expression profiling identified 358 differentially expression genes (DEGs) in the bacterial-resistant group, and 102 DEGs in the bacterial-susceptible group, compared with that in control group. According to the reported references and annotation information from BLAST, GO and KEGG, 30 putative bacterial-resistant genes and 19 putative bacterial-susceptible genes were identified from DEGs. The qRT-PCR results were consistent with the RNA-Seq results. Furthermore, many DGEs were involved in immune signaling related pathways, such as Endocytosis, Lysosome, MAPK, Chemokine and the ERBB signaling pathway.

Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Coelomocytes of Sea Cucumber (Apostichopus japonicus) after Vibrio splendidus Challenge

PubMed Central

Gao, Qiong; Liao, Meijie; Wang, Yingeng; Li, Bin; Zhang, Zheng; Rong, Xiaojun; Chen, Guiping; Wang, Lan

2015-01-01

Vibrio splendidus is identified as one of the major pathogenic factors for the skin ulceration syndrome in sea cucumber (Apostichopus japonicus), which has vastly limited the development of the sea cucumber culture industry. In order to screen the immune genes involving Vibrio splendidus challenge in sea cucumber and explore the molecular mechanism of this process, the related transcriptome and gene expression profiling of resistant and susceptible biotypes of sea cucumber with Vibrio splendidus challenge were collected for analysis. A total of 319,455,942 trimmed reads were obtained, which were assembled into 186,658 contigs. After that, 89,891 representative contigs (without isoform) were clustered. The analysis of the gene expression profiling identified 358 differentially expression genes (DEGs) in the bacterial-resistant group, and 102 DEGs in the bacterial-susceptible group, compared with that in control group. According to the reported references and annotation information from BLAST, GO and KEGG, 30 putative bacterial-resistant genes and 19 putative bacterial-susceptible genes were identified from DEGs. The qRT-PCR results were consistent with the RNA-Seq results. Furthermore, many DGEs were involved in immune signaling related pathways, such as Endocytosis, Lysosome, MAPK, Chemokine and the ERBB signaling pathway. PMID:26193268

[Airway management in Ludwig's angina - a challenge: case report].

PubMed

Fellini, Roberto Taboada; Volquind, Daniel; Schnor, Otávio Haygert; Angeletti, Marcelo Gustavo; Souza, Olívia Egger de

Ludwig's angina (LA) is an infection of the submandibular space, first described by Wilhelm Frederick von Ludwig in 1836. It represents an entity difficult to manage due to the rapid progression and difficulty in maintaining airway patency, a major challenge in medical practice, resulting in asphyxia and death in 8-10% of patients. Describe a case of a patient with Ludwig's angina undergoing surgery, with emphasis on airway management, in addition to reviewing the articles published in the literature on this topic. Male patient, 21 years, drug addict, admitted by the emergency department and diagnosed with LA. Difficult airway was identified during the anesthetic examination. In additional tests, significant deviation from the tracheal axis was seen. Undergoing bilateral thoracoscopic pleural drainage, we opted for airway management through tracheal intubation using fiberoptic bronchoscopy, and balanced general anesthesia was proposed. There were no complications during the surgical-anesthetic act. After the procedure, the patient remained intubated and mechanically ventilated in the intensive care unit. Airway management in patients with Ludwig's angina remains challenging. The choice of the safest technique should be based on clinical signs, technical conditions available, and the urgent need to preserve the patient's life. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Bangladesh Midlife Women's Health Study (BMWHS): methods, challenges and experiences.

PubMed

Islam, Rakibul M; Bell, Robin J; Hossain, Mohammad B; Davis, Susan R

2015-01-01

To understand the challenges and experiences encountered during data collection for Bangladesh Midlife Women's Health Study (BMWHS) that investigated the low uptake of cervical cancer (CCa) screening barriers, understanding of breast cancer (BCa) knowledge and practices, the prevalence of urinary and fecal incontinence and menopausal symptoms. A multistage cluster sampling technique was used to recruit women from the 32 districts of Bangladesh that had offered CCa screening. Female interviewers were trained to undertake structured face-to-face interviews that incorporated both non-validated and several validated questionnaires, such as Question for Urinary Incontinence Diagnosis, Pelvic Organ Prolapse Distress Inventory, Colorectal-Anal Distress Inventory and Menopause-Specific Quality of Life. We completed surveys of 1590 women, estimated age 30-59 years, between September 2013 and March 2014. We implemented several strategies to deal with low literacy and used the temporal relationship between marriage and childbirth, and the average age of onset of menarche, to estimate age. Cultural and religious sensitivities and personal security were managed by engaging community leaders, limiting activities to daylight hours, adopting local codes of dress, such as the wearing of head scarves. Our major challenges and experiences included difficulties in age determination, selection of and access to households, interview privacy, lack of basic and health literacy, transportation, political unrest and security of the interviewers. By anticipating challenges, we have been able to comprehensively survey a representative sample of Bangladeshi women. Disseminating information about the field challenges and experiences from the BMWHS should assist other researchers planning to conduct surveys about women's health issues in similar context. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Overview of Contemporary Issues of Forest Research and Management in China

NASA Astrophysics Data System (ADS)

He, Hong S.; Shifley, Stephen R.; Thompson, Frank R.

2011-12-01

With 207 million ha of forest covering 22% of its land area, China ranks fifth in the world in forest area. Rapid economic growth, climate change, and forest disturbances pose new, complex challenges for forest research and management. Progress in meeting these challenges is relevant beyond China, because China's forests represent 34% of Asia's forests and 5% of the worlds' forests. To provide a broader understanding of these management challenges and of research and policies that address them, we organized this special issue on contemporary forest research and management issues in China. At the national level, papers review major forest types and the evolution of sustainable forestry, the development of China's forest-certification efforts, the establishment of a forest inventory system, and achievements and challenges in insect pest control in China. Papers focused on Northern China address historical, social, and political factors that have shaped the region's forests; the use of forest landscape models to assess how forest management can achieve multiple objectives; and analysis and modeling of fuels and fire behavior. Papers addressing Central and South China describe the "Grain for Green" program, which converts low productivity cropland to grassland and woodland to address erosion and soil carbon sequestration; the potential effects of climate change on CO2 efflux and soil respiration; and relationships between climate and net primary productivity. China shares many forest management and research issues with other countries, but in other cases China's capacity to respond to forest management challenges is unique and bears watching by the rest of the world.

Cyber security challenges in Smart Cities: Safety, security and privacy.

PubMed

Elmaghraby, Adel S; Losavio, Michael M

2014-07-01

The world is experiencing an evolution of Smart Cities. These emerge from innovations in information technology that, while they create new economic and social opportunities, pose challenges to our security and expectations of privacy. Humans are already interconnected via smart phones and gadgets. Smart energy meters, security devices and smart appliances are being used in many cities. Homes, cars, public venues and other social systems are now on their path to the full connectivity known as the "Internet of Things." Standards are evolving for all of these potentially connected systems. They will lead to unprecedented improvements in the quality of life. To benefit from them, city infrastructures and services are changing with new interconnected systems for monitoring, control and automation. Intelligent transportation, public and private, will access a web of interconnected data from GPS location to weather and traffic updates. Integrated systems will aid public safety, emergency responders and in disaster recovery. We examine two important and entangled challenges: security and privacy. Security includes illegal access to information and attacks causing physical disruptions in service availability. As digital citizens are more and more instrumented with data available about their location and activities, privacy seems to disappear. Privacy protecting systems that gather data and trigger emergency response when needed are technological challenges that go hand-in-hand with the continuous security challenges. Their implementation is essential for a Smart City in which we would wish to live. We also present a model representing the interactions between person, servers and things. Those are the major element in the Smart City and their interactions are what we need to protect.

Inference for Distributions over the Permutation Group

DTIC Science & Technology

2008-05-01

world problems, such as voting , ranking, and data association. Representing uncertainty over permutations is challenging, since there are n...problems, such as voting , ranking, and data association. Representing uncertainty over permutations is challenging, since there are n! possibilities...the Krone ker (or Tensor ) Produ t Representation.In general, the Krone ker produ t representation is redu ible, and so it ande omposed into a dire t

Refinement of the MHC Risk Map in a Scandinavian Primary Sclerosing Cholangitis Population

PubMed Central

Næss, Sigrid; Lie, Benedicte A.; Melum, Espen; Olsson, Marita; Hov, Johannes R.; Croucher, Peter J. P.; Hampe, Jochen; Thorsby, Erik; Bergquist, Annika; Traherne, James A.; Schrumpf, Erik; Boberg, Kirsten Muri; Schreiber, Stefan; Franke, Andre; Karlsen, Tom H.

2014-01-01

Background Genetic variants within the major histocompatibility complex (MHC) represent the strongest genetic susceptibility factors for primary sclerosing cholangitis (PSC). Identifying the causal variants within this genetic complex represents a major challenge due to strong linkage disequilibrium and an overall high physical density of candidate variants. We aimed to refine the MHC association in a geographically restricted PSC patient panel. Methodology/Principal Findings A total of 365 PSC cases and 368 healthy controls of Scandinavian ancestry were included in the study. We incorporated data from HLA typing (HLA-A, -B, -C, -DRB3, -DRB1, -DQB1) and single nucleotide polymorphisms across the MHC (n = 18,644; genotyped and imputed) alongside previously suggested PSC risk determinants in the MHC, i.e. amino acid variation of DRβ, a MICA microsatellite polymorphism and HLA-C and HLA-B according to their ligand properties for killer immunoglobulin-like receptors. Breakdowns of the association signal by unconditional and conditional logistic regression analyses demarcated multiple PSC associated MHC haplotypes, and for eight of these classical HLA class I and II alleles represented the strongest association. A novel independent risk locus was detected near NOTCH4 in the HLA class III region, tagged by rs116212904 (odds ratio [95% confidence interval] = 2.32 [1.80, 3.00], P = 1.35×10−11). Conclusions/Significance Our study shows that classical HLA class I and II alleles, predominantly at HLA-B and HLA-DRB1, are the main risk factors for PSC in the MHC. In addition, the present assessments demonstrated for the first time an association near NOTCH4 in the HLA class III region. PMID:25521205

COMPARISON OF ECOLOGICAL COMMUNITIES: THE PROBLEM OF SAMPLE REPRESENTATIVENESS

EPA Science Inventory

Obtaining an adequate, representative sample of ecological communities to make taxon richness (TR) or compositional comparisons among sites is a continuing challenge. Sample representativeness literally means the similarity in species composition and relative abundance between a ...

Creating a Learning Community for Solutions to Climate Change

NASA Astrophysics Data System (ADS)

Bloom, A. J.; Benedict, B. A.; Blockstein, D. E.; Hassenzahl, D. M.; Hunter, A.; Jorgensen, A. D.; Pfirman, S. L.

2011-12-01

The rapidly evolving and interdisciplinary nature of climate change presents a challenge to colleges and universities as they seek to educate undergraduate students. To address this challenge, the National Council for Science and the Environment (NCSE) with NSF funding is creating a nationwide cyber-enabled learning community called CAMEL (Climate, Adaptation, and Mitigation e-Learning). CAMEL engages experts in science, policy and decision-making, education, and assessment in the production of a virtual toolbox of curricular resources designed for teaching climate change causes, consequences, and solutions. CAMEL is: ? Developing cyberinfrastructure that supports and promotes the creation of materials and community; ? Generating materials for the Encyclopedia of Earth, a site averaging 50,000 views per day; ? Ensuring that materials developed and shared are founded on the best available scientific information and follow the most appropriate educational practices; ? Assisting faculty at institutions of higher education across the United States as they create, improve, test, and share resources for teaching students not only how to diagnose climate change problems, but also to identify and effect solutions; ? Evaluating the determinants of successful community building using cybermedia. The community and resultant content range from general education to upper division courses for students in a variety of majors. At the center of the community are the 160 colleges and universities represented in NCSE's Council of Environmental Deans and Directors. Members of this group represent recognized expertise in virtually all areas of this project. A team with substantial experience with evaluating innovative initiatives in STEM education is administering the evaluation component.

A transferable coarse-grained model for diphenylalanine: How to represent an environment driven conformational transition

NASA Astrophysics Data System (ADS)

Dalgicdir, Cahit; Sensoy, Ozge; Peter, Christine; Sayar, Mehmet

2013-12-01

One of the major challenges in the development of coarse grained (CG) simulation models that aim at biomolecular structure formation processes is the correct representation of an environment-driven conformational change, for example, a folding/unfolding event upon interaction with an interface or upon aggregation. In the present study, we investigate this transferability challenge for a CG model using the example of diphenylalanine. This dipeptide displays a transition from a trans-like to a cis-like conformation upon aggregation as well as upon transfer from bulk water to the cyclohexane/water interface. Here, we show that one can construct a single CG model that can reproduce both the bulk and interface conformational behavior and the segregation between hydrophobic/hydrophilic medium. While the general strategy to obtain nonbonded interactions in the present CG model is to reproduce solvation free energies of small molecules representing the CG beads in the respective solvents, the success of the model strongly depends on nontrivial decisions one has to make to capture the delicate balance between the bonded and nonbonded interactions. In particular, we found that the peptide's conformational behavior is qualitatively affected by the cyclohexane/water interaction potential, an interaction that does not directly involve the peptide at all but merely influences the properties of the hydrophobic/hydrophilic interface. Furthermore, we show that a small modification to improve the structural/conformational properties of the CG model could dramatically alter the thermodynamic properties.

Individual tooth macrowear pattern guides the reconstruction of Sts 52 (Australopithecus africanus) dental arches.

PubMed

Benazzi, Stefano; Kullmer, Ottmar; Schulz, Dieter; Gruppioni, Giorgio; Weber, Gerhard W

2013-02-01

The functional restoration of the occlusal relationship between maxillary and mandibular tooth rows is a major challenge in modern dentistry and maxillofacial surgery. Similar technical challenges are present in paleoanthropology when considering fragmented and deformed mandibular and maxillary fossils. Sts 52, an Australopithecus africanus specimen from Sterkfontein Member 4, represents a typical case where the original shape of the dental arches is no longer preserved. It includes a partial lower face (Sts 52a) and a fragmented mandible (Sts 52b), both incomplete and damaged to such an extent to thwart attempts at matching upper and lower dentitions. We show how the preserved macro wear pattern of the tooth crowns can be used to functionally reconstruct Sts 52's dental arches. High-resolution dental stone casts of Sts 52 maxillary and mandibular dentition were mounted and repositioned in a dental articulator. The occlusal relationship between antagonists was restored based on the analysis of the occlusal wear pattern of each preserved tooth, considering all dental contact movements represented in the occlusal compass. The reconstructed dental arches were three-dimensional surface scanned and their occlusal kinematics tested in a simulation. The outcome of this contribution is the first functional restoration of A. africanus dental arches providing new morphometric data for specimen Sts 52. It is noteworthy that the method described in this case study might be applied to several other fossil specimens. Copyright © 2013 Wiley Periodicals, Inc.

Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference.

PubMed

Sahin, Mustafa; Henske, Elizabeth P; Manning, Brendan D; Ess, Kevin C; Bissler, John J; Klann, Eric; Kwiatkowski, David J; Roberds, Steven L; Silva, Alcino J; Hillaire-Clarke, Coryse St; Young, Lisa R; Zervas, Mark; Mamounas, Laura A

2016-07-01

On March 10 to March 12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland, to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program, and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. Here we summarize the outcomes from the extensive premeeting deliberations and final workshop recommendations, including (1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex, (2) the key gaps, needs, and challenges that hinder progress in tuberous sclerosis complex research, and (3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five to ten year time frame. Copyright © 2016 Elsevier Inc. All rights reserved.

25 CFR 90.33 - Watchers and challengers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TRIBE Elections § 90.33 Watchers and challengers. Any candidate or political party may name a person to... watcher and challenger shall be appointed in writing by the candidate or political party he or she represents. The watchers and challengers shall have the right to be present in the polling place but outside...

Tailoring Modified Moore Method Techniques to Liberal Arts Mathematics Courses

ERIC Educational Resources Information Center

Hitchman, Theron J.; Shaw, Douglas

2015-01-01

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

Employing a Multi-level Approach to Recruit a Representative Sample of Women with Recent Gestational Diabetes Mellitus into a Randomized Lifestyle Intervention Trial.

PubMed

Nicklas, Jacinda M; Skurnik, Geraldine; Zera, Chloe A; Reforma, Liberty G; Levkoff, Sue E; Seely, Ellen W

2016-02-01

The postpartum period is a window of opportunity for diabetes prevention in women with recent gestational diabetes (GDM), but recruitment for clinical trials during this period of life is a major challenge. We adapted a social-ecologic model to develop a multi-level recruitment strategy at the macro (high or institutional level), meso (mid or provider level), and micro (individual) levels. Our goal was to recruit 100 women with recent GDM into the Balance after Baby randomized controlled trial over a 17-month period. Participants were asked to attend three in-person study visits at 6 weeks, 6, and 12 months postpartum. They were randomized into a control arm or a web-based intervention arm at the end of the baseline visit at six weeks postpartum. At the end of the recruitment period, we compared population characteristics of our enrolled subjects to the entire population of women with GDM delivering at Brigham and Women's Hospital (BWH). We successfully recruited 107 of 156 (69 %) women assessed for eligibility, with the majority (92) recruited during pregnancy at a mean 30 (SD ± 5) weeks of gestation, and 15 recruited postpartum, at a mean 2 (SD ± 3) weeks postpartum. 78 subjects attended the initial baseline visit, and 75 subjects were randomized into the trial at a mean 7 (SD ± 2) weeks postpartum. The recruited subjects were similar in age and race/ethnicity to the total population of 538 GDM deliveries at BWH over the 17-month recruitment period. Our multilevel approach allowed us to successfully meet our recruitment goal and recruit a representative sample of women with recent GDM. We believe that our most successful strategies included using a dedicated in-person recruiter, integrating recruitment into clinical flow, allowing for flexibility in recruitment, minimizing barriers to participation, and using an opt-out strategy with providers. Although the majority of women were recruited while pregnant, women recruited in the early postpartum period were more likely to present for the first study visit. Given the increased challenges of recruiting postpartum women with GDM into research studies, we believe our findings will be useful to other investigators seeking to study this population.

Immunomodulatory Effects of Dietary Seaweeds in LPS Challenged Atlantic Salmon Salmo salar as Determined by Deep RNA Sequencing of the Head Kidney Transcriptome

PubMed Central

Palstra, Arjan P.; Kals, Jeroen; Blanco Garcia, Ainhoa; Dirks, Ron P.; Poelman, Marnix

2018-01-01

Seaweeds may represent immuno-stimulants that could be used as health-promoting fish feed components. This study was performed to gain insights into the immunomodulatory effects of dietary seaweeds in Atlantic salmon. Specifically tested were 10% inclusion levels of Laminaria digitata (SW1) and a commercial blend of seaweeds (Oceanfeed®) (SW2) against a fishmeal based control diet (FMC). Differences between groups were assessed in growth, feed conversion ratio and blood parameters hematocrit and hemoglobin. After a LPS challenge of fish representing each of the three groups, RNAseq was performed on the head kidney as major immune organ to determine transcriptomic differences in response to the immune activation. Atlantic salmon fed with dietary seaweeds did not show major differences in performance in comparison with fishmeal fed fish. RNAseq resulted in ∼154 million reads which were mapped against a NCBI Salmo salar reference and against a de novo assembled S. salar reference for analyses of expression of immune genes and ontology of immune processes among the 87,600 cDNA contigs. The dietary seaweeds provoked a more efficient immune response which involved more efficient identification of the infection site, and processing and presentation of antigens. More specifically, chemotaxis and the chemokine-mediated signaling were improved and therewith the defense response to Gram-positive bacterium reduced. Specific Laminaria digitata effects included reduction of the interferon-gamma-mediated signaling. Highly upregulated and specific for this diet was the expression of major histocompatibility complex class I-related gene protein. The commercial blend of seaweeds caused more differential expression than Laminaria digitata and improved immune processes such as receptor-mediated endocytosis and cell adhesion, and increased the expression of genes involved in response to lipopolysaccharide and inflammatory response. Particularly, expression of many important immune receptors was up-regulated illustrating increased responsiveness. NF-kappa-B inhibitor alpha is an important gene that marked the difference between both seaweed diets as Laminaria digitata inhibits the expression for this cytokine while the blend of seaweeds stimulates it. It can be concluded that the inclusion of seaweeds such as Laminaria digitata can have important modulatory effects on the immune capacity of Atlantic salmon resulting in a more efficient immune response. PMID:29910738

Interpreting signals from astrophysical transient experiments

PubMed Central

O’Brien, Paul T.; Smartt, Stephen J.

2013-01-01

Time-domain astronomy has come of age with astronomers now able to monitor the sky at high cadence, both across the electromagnetic spectrum and using neutrinos and gravitational waves. The advent of new observing facilities permits new science, but the ever-increasing throughput of facilities demands efficient communication of coincident detections and better subsequent coordination among the scientific community so as to turn detections into scientific discoveries. To discuss the revolution occurring in our ability to monitor the Universe and the challenges it brings, on 25–26 April 2012, a group of scientists from observational and theoretical teams studying transients met with representatives of the major international transient observing facilities at the Kavli Royal Society International Centre, UK. This immediately followed the Royal Society Discussion Meeting ‘New windows on transients across the Universe’ held in London. Here, we present a summary of the Kavli meeting at which the participants discussed the science goals common to the transient astronomy community and analysed how to better meet the challenges ahead as ever more powerful observational facilities come on stream. PMID:23630383

Education and public engagement in observatory operations

NASA Astrophysics Data System (ADS)

Gabor, Pavel; Mayo, Louis; Zaritsky, Dennis

2016-07-01

Education and public engagement (EPE) is an essential part of astronomy's mission. New technologies, remote observing and robotic facilities are opening new possibilities for EPE. A number of projects (e.g., Telescopes In Education, MicroObservatory, Goldstone Apple Valley Radio Telescope and UNC's Skynet) have developed new infrastructure, a number of observatories (e.g., University of Arizona's "full-engagement initiative" towards its astronomy majors, Vatican Observatory's collaboration with high-schools) have dedicated their resources to practical instruction and EPE. Some of the facilities are purpose built, others are legacy telescopes upgraded for remote or automated observing. Networking among institutions is most beneficial for EPE, and its implementation ranges from informal agreements between colleagues to advanced software packages with web interfaces. The deliverables range from reduced data to time and hands-on instruction while operating a telescope. EPE represents a set of tasks and challenges which is distinct from research applications of the new astronomical facilities and operation modes. In this paper we examine the experience with several EPE projects, and some lessons and challenges for observatory operation.

Water Cycle Extremes: from Observations to Decisions

NASA Astrophysics Data System (ADS)

Lawford, R. G.; Unninayar, S.; Berod, D.

2015-12-01

Extremes in the water cycle (droughts and floods) pose major challenges for water resource managers and emergency services. These challenges arise from observational and prediction systems, advisory services, impact reduction strategies, and cleanup and recovery operations. The Group on Earth Observations (GEO) through its Water Strategy ("GEOSS Water Strategy: from observations to decisions") is seeking to provide systems that will enable its members to more effectively meet their information needs prior to and during an extreme event. This presentation reviews the wide range of impacts that arise from extremes in the water cycle and the types of data and information needed to plan for and respond to these extreme events. It identifies the capabilities and limitations of current observational and analysis systems in defining the scale, timing, intensity and impacts of water cycle extremes and in directing society's response to them. This summary represents an early preliminary assessment of the global and regional information needs of water resource managers and begins to outline a strategy within GEO for using Earth Observations and ancillary information to address these needs.

Convolutional Sparse Coding for RGB+NIR Imaging.

PubMed

Hu, Xuemei; Heide, Felix; Dai, Qionghai; Wetzstein, Gordon

2018-04-01

Emerging sensor designs increasingly rely on novel color filter arrays (CFAs) to sample the incident spectrum in unconventional ways. In particular, capturing a near-infrared (NIR) channel along with conventional RGB color is an exciting new imaging modality. RGB+NIR sensing has broad applications in computational photography, such as low-light denoising, it has applications in computer vision, such as facial recognition and tracking, and it paves the way toward low-cost single-sensor RGB and depth imaging using structured illumination. However, cost-effective commercial CFAs suffer from severe spectral cross talk. This cross talk represents a major challenge in high-quality RGB+NIR imaging, rendering existing spatially multiplexed sensor designs impractical. In this work, we introduce a new approach to RGB+NIR image reconstruction using learned convolutional sparse priors. We demonstrate high-quality color and NIR imaging for challenging scenes, even including high-frequency structured NIR illumination. The effectiveness of the proposed method is validated on a large data set of experimental captures, and simulated benchmark results which demonstrate that this work achieves unprecedented reconstruction quality.

Nanotechnology-Based Strategies for Early Cancer Diagnosis Using Circulating Tumor Cells as a Liquid Biopsy

PubMed Central

Huang, Qinqin; Wang, Yin; Chen, Xingxiang; Wang, Yimeng; Li, Zhiqiang; Du, Shiming; Wang, Lianrong; Chen, Shi

2018-01-01

Circulating tumor cells (CTCs) are cancer cells that shed from a primary tumor and circulate in the bloodstream. As a form of “tumor liquid biopsy”, CTCs provide important information for the mechanistic investigation of cancer metastasis and the measurement of tumor genotype evolution during treatment and disease progression. However, the extremely low abundance of CTCs in the peripheral blood and the heterogeneity of CTCs make their isolation and characterization major technological challenges. Recently, nanotechnologies have been developed for sensitive CTC detection; such technologies will enable better cell and molecular characterization and open up a wide range of clinical applications, including early disease detection and evaluation of treatment response and disease progression. In this review, we summarize the nanotechnology-based strategies for CTC isolation, including representative nanomaterials (such as magnetic nanoparticles, gold nanoparticles, silicon nanopillars, nanowires, nanopillars, carbon nanotubes, dendrimers, quantum dots, and graphene oxide) and microfluidic chip technologies that incorporate nanoroughened surfaces and discuss their key challenges and perspectives in CTC downstream analyses, such as protein expression and genetic mutations that may reflect tumor aggressiveness and patient outcome. PMID:29291161

Face transplant: is it feasible in developing countries?

PubMed

González-García, Ignacio; Lyra-González, Iván; Medina-Preciado, David; Guerrero-Torres, Alejandro; Ramos-Gallardo, Guillermo; Armendáriz-Borunda, Juan

2013-01-01

This article is based on the case of a 28-year-old woman who was involved in a car accident, with diagnosis of polytrauma, loss of left eye, and second- and third-degree burns over the left midface, rendering an exposed area of 8 cm wide and 19 cm length, ranging from glabella to mandible, with skull exposure and loss of left eye.A latissimus dorsi musculocutaneous free flap was transferred into the defect; left eye and nose prosthetics were necessary to restore normal appearance. Excellent results were obtained; reinsertion to patient's normal life and reinstatement of facial appearance were achieved with minimal costs and no postsurgical complications.Analysis of the current situation in developing countries demonstrates that technique and infrastructure do not represent a real challenge to carry on face transplants. However, socioeconomic reality in these societies makes it difficult to establish face transplant as a feasible therapeutic opportunity for the overwhelming majority of patients who are victims of severe facial damage.Therefore, strategies such as latissimus dorsi free flap remains as an excellent therapy to face off our complex facial reconstructive challenges in developing countries such as Mexico.

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.

Challenges to Applying a Metamodel for Groundwater Flow Beyond Underlying Numerical Model Boundaries

NASA Astrophysics Data System (ADS)

Reeves, H. W.; Fienen, M. N.; Feinstein, D.

2015-12-01

Metamodels of environmental behavior offer opportunities for decision support, adaptive management, and increased stakeholder engagement through participatory modeling and model exploration. Metamodels are derived from calibrated, computationally demanding, numerical models. They may potentially be applied to non-modeled areas to provide screening or preliminary analysis tools for areas that do not yet have the benefit of more comprehensive study. In this decision-support mode, they may be fulfilling a role often accomplished by application of analytical solutions. The major challenge to transferring a metamodel to a non-modeled area is how to quantify the spatial data in the new area of interest in such a way that it is consistent with the data used to derive the metamodel. Tests based on transferring a metamodel derived from a numerical groundwater-flow model of the Lake Michigan Basin to other glacial settings across the northern U.S. show that the spatial scale of the numerical model must be appropriately scaled to adequately represent different settings. Careful GIS analysis of the numerical model, metamodel, and new area of interest is required for successful transfer of results.

Detection of urban expansion in an urban-rural landscape with multitemporal QuickBird images

PubMed Central

Lu, Dengsheng; Hetrick, Scott; Moran, Emilio; Li, Guiying

2011-01-01

Accurately detecting urban expansion with remote sensing techniques is a challenge due to the complexity of urban landscapes. This paper explored methods for detecting urban expansion with multitemporal QuickBird images in Lucas do Rio Verde, Mato Grosso, Brazil. Different techniques, including image differencing, principal component analysis (PCA), and comparison of classified impervious surface images with the matched filtering method, were used to examine urbanization detection. An impervious surface image classified with the hybrid method was used to modify the urbanization detection results. As a comparison, the original multispectral image and segmentation-based mean-spectral images were used during the detection of urbanization. This research indicates that the comparison of classified impervious surface images with matched filtering method provides the best change detection performance, followed by the image differencing method based on segmentation-based mean spectral images. The PCA is not a good method for urban change detection in this study. Shadows and high spectral variation within the impervious surfaces represent major challenges to the detection of urban expansion when high spatial resolution images are used. PMID:21799706

Untethered Recyclable Tubular Actuators with Versatile Locomotion for Soft Continuum Robots.

PubMed

Qian, Xiaojie; Chen, Qiaomei; Yang, Yang; Xu, Yanshuang; Li, Zhen; Wang, Zhenhua; Wu, Yahe; Wei, Yen; Ji, Yan

2018-05-27

Stimuli-responsive materials offer a distinguished platform to build tether-free compact soft robots, which can combine sensing and actuation without a linked power supply. In the past, tubular soft robots have to be made by multiple components with various internal channels or complex cavities assembled together. Moreover, robust processing, complex locomotion, simple structure, and easy recyclability represent major challenges in this area. Here, it is shown that those challenges can be tackled by liquid crystalline elastomers with allyl sulfide functional groups. The light-controlled exchange reaction between allyl sulfide groups allows flexible processing of tubular soft robots/actuators, which does not need any assisting materials. Complex locomotion demonstrated here includes reversible simultaneous bending and elongation; reversible diameter expansion; and omnidirectional bending via remote infrared light control. Different modes of actuation can be programmed into the same tube without the routine assembly of multiple tubes as used in the past. In addition, the exchange reaction also makes it possible to use the same single tube repeatedly to perform different functions by erasing and reprogramming. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Satellite tracking of manta rays highlights challenges to their conservation.

PubMed

Graham, Rachel T; Witt, Matthew J; Castellanos, Dan W; Remolina, Francisco; Maxwell, Sara; Godley, Brendan J; Hawkes, Lucy A

2012-01-01

We describe the real-time movements of the last of the marine mega-vertebrate taxa to be satellite tracked - the giant manta ray (or devil fish, Manta birostris), the world's largest ray at over 6 m disc width. Almost nothing is known about manta ray movements and their environmental preferences, making them one of the least understood of the marine mega-vertebrates. Red listed by the International Union for the Conservation of Nature as 'Vulnerable' to extinction, manta rays are known to be subject to direct and incidental capture and some populations are declining. Satellite-tracked manta rays associated with seasonal upwelling events and thermal fronts off the Yucatan peninsula, Mexico, and made short-range shuttling movements, foraging along and between them. The majority of locations were received from waters shallower than 50 m deep, representing thermally dynamic and productive waters. Manta rays remained in the Mexican Exclusive Economic Zone for the duration of tracking but only 12% of tracking locations were received from within Marine Protected Areas (MPAs). Our results on the spatio-temporal distribution of these enigmatic rays highlight opportunities and challenges to management efforts.

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.

Racial and Gender Issues with Physics in the Pacific Region

NASA Astrophysics Data System (ADS)

Aung, Than; Singh, Awnesh; Prasad, Uma

2011-09-01

This paper examines the state of physics teaching and learning in the Pacific Island nations. How have things changed in teaching physics? We believe that some of the goals and many of the challenges faced today have changed very little over the years. This paper is purely based upon the authors' experiences in teaching physics at the first-year level at the University of the South Pacific (USP). USP is a typical medium-sized teaching and research university as compared to universities internationally. In the Pacific, it is the biggest university and is effectively serving the 12 Pacific Island nations. Consequently, the findings described here should represent the overall situation for the Pacific region. Perhaps some of our results will resonate with readers in other locations as well. Worldwide, university students often find studying physics to be very challenging, and only a small fraction of them choose physics as a major for their degree or as a career. Students at USP are not an exception, and here we describe the severity of the problem.

Telehealth for Persons with Severe Functional Disabilities and their Caregivers: Facilitating Self-care Management in the Home Setting

PubMed Central

Forducey, Pamela G.; Glueckauf, Robert L.; Bergquist, Thomas; Maheu, Marlene M.; Yutsis, Maya

2012-01-01

Persons with severe functional disabilities are the highest users of health care services. Caring for the needs of this population represents a significant percentage of our national health care costs. A growing body of research has demonstrated the efficacy of self-management strategies and caregiver engagement for effective long-term care for individuals with chronic medical conditions. Economic forces over the past decade have led to new challenges and resulted in major changes in health care delivery resulting in shortened length of inpatient stays and greater limits on the length of outpatient treatment. Telehealth is an innovative method for health care delivery and a means of meeting this new challenge. This paper highlights the findings of three pilot studies on the use of telecommunications technologies in promoting self-care management and enhancing health care outcomes in persons with severe disabilities and their family caregivers. The importance of matching technology to the needs of this population, lessons learned from these investigations, and future directions for research are addressed. PMID:22662729

Combining human and machine intelligence to derive agents' behavioral rules for groundwater irrigation

NASA Astrophysics Data System (ADS)

Hu, Yao; Quinn, Christopher J.; Cai, Ximing; Garfinkle, Noah W.

2017-11-01

For agent-based modeling, the major challenges in deriving agents' behavioral rules arise from agents' bounded rationality and data scarcity. This study proposes a "gray box" approach to address the challenge by incorporating expert domain knowledge (i.e., human intelligence) with machine learning techniques (i.e., machine intelligence). Specifically, we propose using directed information graph (DIG), boosted regression trees (BRT), and domain knowledge to infer causal factors and identify behavioral rules from data. A case study is conducted to investigate farmers' pumping behavior in the Midwest, U.S.A. Results show that four factors identified by the DIG algorithm- corn price, underlying groundwater level, monthly mean temperature and precipitation- have main causal influences on agents' decisions on monthly groundwater irrigation depth. The agent-based model is then developed based on the behavioral rules represented by three DIGs and modeled by BRTs, and coupled with a physically-based groundwater model to investigate the impacts of agents' pumping behavior on the underlying groundwater system in the context of coupled human and environmental systems.

"It is easier for me to shoot up": stigma, abandonment, and why HIV-positive drug users in Russia fail to link to HIV care.

PubMed

Kiriazova, Tetiana; Lunze, Karsten; Raj, Anita; Bushara, Natalia; Blokhina, Elena; Krupitsky, Evgeny; Bridden, Carly; Lioznov, Dmitry; Samet, Jeffrey H; Gifford, Allen L

2017-05-01

Many HIV-positive people who inject drugs (PWID) globally are not receiving HIV care. This represents a major challenge among key populations to end the global HIV epidemic. This qualitative study explored the process and associated barriers of linking HIV-positive PWID who are in addiction treatment to HIV care in St. Petersburg, Russia. We conducted three focus groups and seven semi-structured interviews with participants in the LINC ("Linking Infectious and Narcology Care") project at addiction and HIV hospitals in St. Petersburg. The sample consisted of 25 HIV-infected patients with opioid dependence and seven health-care providers, including addiction and infectious disease physicians and case managers. A variety of intertwining factors influence effective engagement of PWID with HIV treatment. Stigma, problematic patient-provider relationships, and fragmented health care were the main challenges for HIV care initiation by PWID, which were further exacerbated by injection drug use. Effective linkage of PWID to HIV care requires acknowledging and addressing stigma's role and different perspectives of patients and providers.

Management of intracerebral hemorrhage.

PubMed

Thabet, A M; Kottapally, M; Hemphill, J Claude

2017-01-01

Intracerebral hemorrhage (ICH) is a potentially devastating neurologic injury representing 10-15% of stroke cases in the USA each year. Numerous risk factors, including age, hypertension, male gender, coagulopathy, genetic susceptibility, and ethnic descent, have been identified. Timely identification, workup, and management of this condition remain a challenge for clinicians as numerous factors can present obstacles to achieving good functional outcomes. Several large clinical trials have been conducted over the prior decade regarding medical and surgical interventions. However, no specific treatment has shown a major impact on clinical outcome. Current management guidelines do exist based on medical evidence and consensus and these provide a framework for care. While management of hypertension and coagulopathy are generally considered basic tenets of ICH management, a variety of measures for surgical hematoma evacuation, intracranial pressure control, and intraventricular hemorrhage can be further pursued in the emergent setting for selected patients. The complexity of management in parenchymal cerebral hemorrhage remains challenging and offers many areas for further investigation. A systematic approach to the background, pathology, and early management of spontaneous parenchymal hemorrhage is provided. © 2017 Elsevier B.V. All rights reserved.

Challenges and disparities in the application of personalized genomic medicine to populations with African ancestry

PubMed Central

Kessler, Michael D.; Yerges-Armstrong, Laura; Taub, Margaret A.; Shetty, Amol C.; Maloney, Kristin; Jeng, Linda Jo Bone; Ruczinski, Ingo; Levin, Albert M.; Williams, L. Keoki; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.; Boorgula, Meher Preethi; Campbell, Monica; Chavan, Sameer; Ford, Jean G.; Foster, Cassandra; Gao, Li; Hansel, Nadia N.; Horowitz, Edward; Huang, Lili; Ortiz, Romina; Potee, Joseph; Rafaels, Nicholas; Scott, Alan F.; Vergara, Candelaria; Gao, Jingjing; Hu, Yijuan; Johnston, Henry Richard; Qin, Zhaohui S.; Padhukasahasram, Badri; Dunston, Georgia M.; Faruque, Mezbah U.; Kenny, Eimear E.; Gietzen, Kimberly; Hansen, Mark; Genuario, Rob; Bullis, Dave; Lawley, Cindy; Deshpande, Aniket; Grus, Wendy E.; Locke, Devin P.; Foreman, Marilyn G.; Avila, Pedro C.; Grammer, Leslie; Kim, Kwang-YounA; Kumar, Rajesh; Schleimer, Robert; Bustamante, Carlos; De La Vega, Francisco M.; Gignoux, Chris R.; Shringarpure, Suyash S.; Musharoff, Shaila; Wojcik, Genevieve; Burchard, Esteban G.; Eng, Celeste; Gourraud, Pierre-Antoine; Hernandez, Ryan D.; Lizee, Antoine; Pino-Yanes, Maria; Torgerson, Dara G.; Szpiech, Zachary A.; Torres, Raul; Nicolae, Dan L.; Ober, Carole; Olopade, Christopher O.; Olopade, Olufunmilayo; Oluwole, Oluwafemi; Arinola, Ganiyu; Song, Wei; Abecasis, Goncalo; Correa, Adolfo; Musani, Solomon; Wilson, James G.; Lange, Leslie A.; Akey, Joshua; Bamshad, Michael; Chong, Jessica; Fu, Wenqing; Nickerson, Deborah; Reiner, Alexander; Hartert, Tina; Ware, Lorraine B.; Bleecker, Eugene; Meyers, Deborah; Ortega, Victor E.; Pissamai, Maul R. N.; Trevor, Maul R. N.; Watson, Harold; Araujo, Maria Ilma; Oliveira, Ricardo Riccio; Caraballo, Luis; Marrugo, Javier; Martinez, Beatriz; Meza, Catherine; Ayestas, Gerardo; Herrera-Paz, Edwin Francisco; Landaverde-Torres, Pamela; Erazo, Said Omar Leiva; Martinez, Rosella; Mayorga, Alvaro; Mayorga, Luis F.; Mejia-Mejia, Delmy-Aracely; Ramos, Hector; Saenz, Allan; Varela, Gloria; Vasquez, Olga Marina; Ferguson, Trevor; Knight-Madden, Jennifer; Samms-Vaughan, Maureen; Wilks, Rainford J.; Adegnika, Akim; Ateba-Ngoa, Ulysse; Yazdanbakhsh, Maria; O'Connor, Timothy D.

2016-01-01

To characterize the extent and impact of ancestry-related biases in precision genomic medicine, we use 642 whole-genome sequences from the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) project to evaluate typical filters and databases. We find significant correlations between estimated African ancestry proportions and the number of variants per individual in all variant classification sets but one. The source of these correlations is highlighted in more detail by looking at the interaction between filtering criteria and the ClinVar and Human Gene Mutation databases. ClinVar's correlation, representing African ancestry-related bias, has changed over time amidst monthly updates, with the most extreme switch happening between March and April of 2014 (r=0.733 to r=−0.683). We identify 68 SNPs as the major drivers of this change in correlation. As long as ancestry-related bias when using these clinical databases is minimally recognized, the genetics community will face challenges with implementation, interpretation and cost-effectiveness when treating minority populations. PMID:27725664

Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer: A Randomized Trial Comparing Two Radiation Doses

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

Jakobsen, Anders, E-mail: anders.jakobsen@slb.regionsyddanmark.dk; University of Southern Denmark, Odense; Ploen, John

2012-11-15

Purpose: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation. Methods and Materials: The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of {<=}5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; armmore » B). Concomitant chemotherapy, uftoral 300 mg/m{sup 2} and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0). Results: The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04). Conclusions: This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.« less

Optically-based Sensor System for Critical Nuclear Facilities Post-Event Seismic Structural Assessment

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

McCallen, David; Petrone, Floriana; Buckle, Ian

The U.S. Department of Energy (DOE) has ownership and operational responsibility for a large enterprise of nuclear facilities that provide essential functions to DOE missions ranging from national security to discovery science and energy research. These facilities support a number of DOE programs and offices including the National Nuclear Security Administration, Office of Science, and Office of Environmental Management. With many unique and “one of a kind” functions, these facilities represent a tremendous national investment, and assuring their safety and integrity is fundamental to the success of a breadth of DOE programs. Many DOE critical facilities are located in regionsmore » with significant natural phenomenon hazards including major earthquakes and DOE has been a leader in developing standards for the seismic analysis of nuclear facilities. Attaining and sustaining excellence in nuclear facility design and management must be a core competency of the DOE. An important part of nuclear facility management is the ability to monitor facilities and rapidly assess the response and integrity of the facilities after any major upset event. Experience in the western U.S. has shown that understanding facility integrity after a major earthquake is a significant challenge which, lacking key data, can require extensive effort and significant time. In the work described in the attached report, a transformational approach to earthquake monitoring of facilities is described and demonstrated. An entirely new type of optically-based sensor that can directly and accurately measure the earthquake-induced deformations of a critical facility has been developed and tested. This report summarizes large-scale shake table testing of the sensor concept on a representative steel frame building structure, and provides quantitative data on the accuracy of the sensor measurements.« less

BreedVision--a multi-sensor platform for non-destructive field-based phenotyping in plant breeding.

PubMed

Busemeyer, Lucas; Mentrup, Daniel; Möller, Kim; Wunder, Erik; Alheit, Katharina; Hahn, Volker; Maurer, Hans Peter; Reif, Jochen C; Würschum, Tobias; Müller, Joachim; Rahe, Florian; Ruckelshausen, Arno

2013-02-27

To achieve the food and energy security of an increasing World population likely to exceed nine billion by 2050 represents a major challenge for plant breeding. Our ability to measure traits under field conditions has improved little over the last decades and currently constitutes a major bottleneck in crop improvement. This work describes the development of a tractor-pulled multi-sensor phenotyping platform for small grain cereals with a focus on the technological development of the system. Various optical sensors like light curtain imaging, 3D Time-of-Flight cameras, laser distance sensors, hyperspectral imaging as well as color imaging are integrated into the system to collect spectral and morphological information of the plants. The study specifies: the mechanical design, the system architecture for data collection and data processing, the phenotyping procedure of the integrated system, results from field trials for data quality evaluation, as well as calibration results for plant height determination as a quantified example for a platform application. Repeated measurements were taken at three developmental stages of the plants in the years 2011 and 2012 employing triticale (×Triticosecale Wittmack L.) as a model species. The technical repeatability of measurement results was high for nearly all different types of sensors which confirmed the high suitability of the platform under field conditions. The developed platform constitutes a robust basis for the development and calibration of further sensor and multi-sensor fusion models to measure various agronomic traits like plant moisture content, lodging, tiller density or biomass yield, and thus, represents a major step towards widening the bottleneck of non-destructive phenotyping for crop improvement and plant genetic studies.

BreedVision — A Multi-Sensor Platform for Non-Destructive Field-Based Phenotyping in Plant Breeding

PubMed Central

Busemeyer, Lucas; Mentrup, Daniel; Möller, Kim; Wunder, Erik; Alheit, Katharina; Hahn, Volker; Maurer, Hans Peter; Reif, Jochen C.; Würschum, Tobias; Müller, Joachim; Rahe, Florian; Ruckelshausen, Arno

2013-01-01

To achieve the food and energy security of an increasing World population likely to exceed nine billion by 2050 represents a major challenge for plant breeding. Our ability to measure traits under field conditions has improved little over the last decades and currently constitutes a major bottleneck in crop improvement. This work describes the development of a tractor-pulled multi-sensor phenotyping platform for small grain cereals with a focus on the technological development of the system. Various optical sensors like light curtain imaging, 3D Time-of-Flight cameras, laser distance sensors, hyperspectral imaging as well as color imaging are integrated into the system to collect spectral and morphological information of the plants. The study specifies: the mechanical design, the system architecture for data collection and data processing, the phenotyping procedure of the integrated system, results from field trials for data quality evaluation, as well as calibration results for plant height determination as a quantified example for a platform application. Repeated measurements were taken at three developmental stages of the plants in the years 2011 and 2012 employing triticale (×Triticosecale Wittmack L.) as a model species. The technical repeatability of measurement results was high for nearly all different types of sensors which confirmed the high suitability of the platform under field conditions. The developed platform constitutes a robust basis for the development and calibration of further sensor and multi-sensor fusion models to measure various agronomic traits like plant moisture content, lodging, tiller density or biomass yield, and thus, represents a major step towards widening the bottleneck of non-destructive phenotyping for crop improvement and plant genetic studies. PMID:23447014

Translational Challenges in Cardiovascular Tissue Engineering.

PubMed

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

2017-04-01

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

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

PubMed

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

2013-01-01

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

Comparison of the humoral and cellular immune responses between body and head lice following bacterial challenge.

PubMed

Kim, Ju Hyeon; Min, Jee Sun; Kang, Jae Soon; Kwon, Deok Ho; Yoon, Kyong Sup; Strycharz, Joseph; Koh, Young Ho; Pittendrigh, Barry Robert; Clark, J Marshall; Lee, Si Hyeock

2011-05-01

The differences in the immune response between body lice, Pediculus humanus humanus, and head lice, Pediculus humanus capitis, were investigated initially by measuring the proliferation rates of two model bacteria, a Gram-positive Staphylococcus aureus and a Gram-negative Escherichia coli, following challenge by injection. Body lice showed a significantly reduced immune response compared to head lice particularly to E. coli at the early stage of the immune challenge. Annotation of the body louse genome identified substantially fewer immune-related genes compared with other insects. Nevertheless, all required genetic components of the major immune pathways, except for the immune deficiency (Imd) pathway, are still retained in the body louse genome. Transcriptional profiling of representative genes involved in the humoral immune response, following bacterial challenge, revealed that both body and head lice, regardless of their developmental stages, exhibited an increased immune response to S. aureus but little to E. coli. Head lice, however, exhibited a significantly higher phagocytotic activity against E. coli than body lice, whereas the phagocytosis against S. aureus differed only slightly between body and head lice. These findings suggest that the greater immune response in head lice against E. coli is largely due to enhanced phagocytosis and not due to differences in the humoral immune response. The reduced phagocytotic activity in body lice could be responsible, in part, for their increased vector competence. Copyright © 2011 Elsevier Ltd. All rights reserved.

Environmental effectiveness of swine sewage management: a multicriteria AHP-based model for a reliable quick assessment.

PubMed

Vizzari, Marco; Modica, Giuseppe

2013-10-01

Environmental issues related to swine production are still a major concern for the general public and represent a key challenge for the swine industry. The environmental impact of higher livestock concentration is particularly significant where it coincides with weaker policy standards and poor manure management. Effective tools for environmental monitoring of the swine sewage management process become essential for verifying the environmental compatibility of farming facilities and for defining suitable policies aimed at increasing swine production sustainability. This research aims at the development and application of a model for a quick assessment of the environmental effectiveness of the pig farming sewage management process. In order to define the model, multicriteria techniques, and in particular, Saaty's analytic hierarchy process, were used to develop an iterative process in which the various key factors influencing the process under investigation were analyzed. The model, named EASE (Environmental Assessment of Sewages management Effectiveness), was optimized and applied to the Lake Trasimeno basin (Umbria, Italy), an area of high natural, environmental and aesthetic value. In this context, inadequate disposal of pig sewage represents a potential source of very considerable pollution. The results have demonstrated how the multicriteria model can represent a very effective and adaptable tool also in those decision-making processes aimed at the sustainable management of livestock production.

Environmental Effectiveness of Swine Sewage Management: A Multicriteria AHP-Based Model for a Reliable Quick Assessment

NASA Astrophysics Data System (ADS)

Vizzari, Marco; Modica, Giuseppe

2013-10-01

Environmental issues related to swine production are still a major concern for the general public and represent a key challenge for the swine industry. The environmental impact of higher livestock concentration is particularly significant where it coincides with weaker policy standards and poor manure management. Effective tools for environmental monitoring of the swine sewage management process become essential for verifying the environmental compatibility of farming facilities and for defining suitable policies aimed at increasing swine production sustainability. This research aims at the development and application of a model for a quick assessment of the environmental effectiveness of the pig farming sewage management process. In order to define the model, multicriteria techniques, and in particular, Saaty's analytic hierarchy process, were used to develop an iterative process in which the various key factors influencing the process under investigation were analyzed. The model, named EASE (Environmental Assessment of Sewages management Effectiveness), was optimized and applied to the Lake Trasimeno basin (Umbria, Italy), an area of high natural, environmental and aesthetic value. In this context, inadequate disposal of pig sewage represents a potential source of very considerable pollution. The results have demonstrated how the multicriteria model can represent a very effective and adaptable tool also in those decision-making processes aimed at the sustainable management of livestock production.

From Assistant Teacher to Teacher: Challenges and Pathways in Situated Pre-Service Teacher Education

ERIC Educational Resources Information Center

Strangeways, Al

2017-01-01

Vocational pathways to Higher Education have a key role in opening teacher education to under-represented groups but bring with them particular challenges. Teacher educators need to address the challenges faced by these learners, of not only connecting their learning but also challenging their knowledge, and doing so in an invested work…

Methodological approaches for monitoring opportunistic pathogens in premise plumbing: A review.

PubMed

Wang, Hong; Bédard, Emilie; Prévost, Michèle; Camper, Anne K; Hill, Vincent R; Pruden, Amy

2017-06-15

Opportunistic premise (i.e., building) plumbing pathogens (OPPPs, e.g., Legionella pneumophila, Mycobacterium avium complex, Pseudomonas aeruginosa, Acanthamoeba, and Naegleria fowleri) are a significant and growing source of disease. Because OPPPs establish and grow as part of the native drinking water microbiota, they do not correspond to fecal indicators, presenting a major challenge to standard drinking water monitoring practices. Further, different OPPPs present distinct requirements for sampling, preservation, and analysis, creating an impediment to their parallel detection. The aim of this critical review is to evaluate the state of the science of monitoring OPPPs and identify a path forward for their parallel detection and quantification in a manner commensurate with the need for reliable data that is informative to risk assessment and mitigation. Water and biofilm sampling procedures, as well as factors influencing sample representativeness and detection sensitivity, are critically evaluated with respect to the five representative bacterial and amoebal OPPPs noted above. Available culturing and molecular approaches are discussed in terms of their advantages, limitations, and applicability. Knowledge gaps and research needs towards standardized approaches are identified. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tracking with occlusions via graph cuts.

PubMed

Papadakis, Nicolas; Bugeau, Aurélie

2011-01-01

This work presents a new method for tracking and segmenting along time-interacting objects within an image sequence. One major contribution of the paper is the formalization of the notion of visible and occluded parts. For each object, we aim at tracking these two parts. Assuming that the velocity of each object is driven by a dynamical law, predictions can be used to guide the successive estimations. Separating these predicted areas into good and bad parts with respect to the final segmentation and representing the objects with their visible and occluded parts permit handling partial and complete occlusions. To achieve this tracking, a label is assigned to each object and an energy function representing the multilabel problem is minimized via a graph cuts optimization. This energy contains terms based on image intensities which enable segmenting and regularizing the visible parts of the objects. It also includes terms dedicated to the management of the occluded and disappearing areas, which are defined on the areas of prediction of the objects. The results on several challenging sequences prove the strength of the proposed approach.

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

PubMed Central

Porsbjerg, Celeste; Ulrik, Charlotte; Skjold, Tina; Backer, Vibeke; Laerum, Birger; Lehman, Sverre; Janson, Crister; Sandstrøm, Thomas; Bjermer, Leif; Dahlen, Barbro; Lundbäck, Bo; Ludviksdottir, Dora; Björnsdóttir, Unnur; Altraja, Alan; Lehtimäki, Lauri; Kauppi, Paula; Karjalainen, Jussi; Kankaanranta, Hannu

2018-01-01

ABSTRACT Although a minority of asthma patients suffer from severe asthma, they represent a major clinical challenge in terms of poor symptom control despite high-dose treatment, risk of exacerbations, and side effects. Novel biological treatments may benefit patients with severe asthma, but are expensive, and are only effective in appropriately targeted patients. In some patients, symptoms are driven by other factors than asthma, and all patients with suspected severe asthma (‘difficult asthma’) should undergo systematic assessment, in order to differentiate between true severe asthma, and ‘difficult-to-treat’ patients, in whom poor control is related to factors such as poor adherence or co-morbidities. The Nordic Consensus Statement on severe asthma was developed by the Nordic Severe Asthma Network, consisting of members from Norway, Sweden, Finland, Denmark, Iceland and Estonia, including representatives from the respective national respiratory scientific societies with the aim to provide an overview and recommendations regarding the diagnosis, systematic assessment and management of severe asthma. Furthermore, the Consensus Statement proposes recommendations for the organization of severe asthma management in primary, secondary, and tertiary care. PMID:29535852

Characterization of methicillin-resistant Staphylococcus aureus isolated at Tripoli Medical Center, Libya, between 2008 and 2014.

PubMed

BenDarif, Elloulu; Khalil, Asma; Rayes, Abdunnabi; Bennour, Emad; Dhawi, Abdulgader; Lowe, John J; Gibbs, Shawn; Goering, Richard V

2016-12-01

Bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) represent a well-known public health problem affecting both healthcare-associated and community populations. Past studies have clearly shown the value of characterizing problem organisms including MRSA through the use of molecular techniques (i.e. strain typing), with the aim of informing local, regional and national efforts in epidemiological analysis and infection control. The country of Libya represents a challenge for such analysis due to limited historical infectious disease information and major political unrest culminating in the Libyan Civil War (Libyan Revolution) in 2011. A MRSA study population of 202 isolates, cultured from patients in Tripoli Medical Center through this historical period (2008-2014), was characterized by both phenotypic and molecular methods. The results revealed a diversification of epidemic MRSA strains over time with generally increasing resistance to fluoroquinolone antibiotics. The study identified prevalent MRSA in comparison to known global epidemic types, providing unique insight into the change of strains and/or characteristics over time especially with reference to the potential influence of the political revolution (i.e. pre- and post-2011).

Proteomic Comparison and MRM-Based Comparative Analysis of Metabolites Reveal Metabolic Shift in Human Prostate Cancer Cell Lines.

PubMed

Shu, Qingbo; Cai, Tanxi; Chen, Xiulan; Zhu, Helen He; Xue, Peng; Zhu, Nali; Xie, Zhensheng; Wei, Shasha; Zhang, Qing; Niu, Lili; Gao, Wei-Qiang; Yang, Fuquan

2015-08-07

One of the major challenges in prostate cancer therapy remains the development of effective treatments for castration-resistant prostate cancer (CRPC), as the underlying mechanisms for its progression remain elusive. Previous studies showed that androgen receptor (AR) is crucially involved in regulation of metabolism in prostate cancer (PCa) cells throughout the transition from early stage, androgen-sensitive PCa to androgen-independent CRPC. AR achieves such metabolic rewiring directively either via its transcriptional activity or via interactions with AMP-activated protein kinase (AMPK). However, due to the heterogeneous expression and activity status of AR in PCa cells, it remains a challenge to investigate the links between AR status and metabolic alterations. To this end, we compared the proteomes of three pairs of androgen-sensitive (AS) and androgen-independent (AI) PCa cell lines, namely, PC3-AR(+)/PC3, 22Rv1/Du145, and LNCaP/C42B, using an iTRAQ labeling approach. Our results revealed that most of the differentially expressed proteins between each pair function in metabolism, indicating a metabolic shift between AS and AI cells, as further validated by multiple reaction monitoring (MRM)-based quantification of nucleotides and relative comparison of fatty acids between these cell lines. Furthermore, increased adenylate kinase isoenzyme 1 (AK1) in AS relative to AI cells may result in activation of AMPK, representing a major regulatory factor involved in the observed metabolic shift in PCa cells.

SOFIA Program SE and I Lessons Learned

NASA Technical Reports Server (NTRS)

Ray, Ronald J.; Fobel, Laura J.; Brignola, Michael P.

2011-01-01

Once a "Troubled Project" threatened with cancellation, the Stratospheric Observatory for Infrared Astronomy (SOFIA) Program has overcome many difficult challenges and recently achieved its first light images. To achieve success, SOFIA had to overcome significant deficiencies in fundamental Systems Engineering identified during a major Program restructuring. This presentation will summarize the lessons learn in Systems Engineering on the SOFIA Program. After the Program was reformulated, an initial assessment of Systems Engineering established the scope of the problem and helped to set a list of priorities that needed to be work. A revised Systems Engineering Management Plan (SEMP) was written to address the new Program structure and requirements established in the approved NPR7123.1A. An important result of the "Technical Planning" effort was the decision by the Program and Technical Leadership team to re-phasing the lifecycle into increments. The reformed SOFIA Program Office had to quickly develop and establish several new System Engineering core processes including; Requirements Management, Risk Management, Configuration Management and Data Management. Implementing these processes had to consider the physical and cultural diversity of the SOFIA Program team which includes two Projects spanning two NASA Centers, a major German partnership, and sub-contractors located across the United States and Europe. The SOFIA Program experience represents a creative approach to doing "System Engineering in the middle" while a Program is well established. Many challenges were identified and overcome. The SOFIA example demonstrates it is never too late to benefit from fixing deficiencies in the System Engineering processes.

In vivo microrobots for natural orifice transluminal surgery. Current status and future perspectives.

PubMed

Forgione, A

2009-06-01

The possibility to operate inside the peritoneal cavity through small holes performed in hollow organs that is presented by Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a major paradigm shift in general surgery. While this new approach seems very appealing from patients' perspectives because it eliminates completely abdominal wall aggression and promises to reduce postoperative pain, it is very challenging for surgeons because of the major constraints imposed by both the mode of access and the limited technology currently available. For this reason NOTES applications at the present time are performed by only a few surgeons and mainly to perform non-complex procedures. While new devices are under development, many of them are trying mainly to simply improve current endoscopic platforms and seem not to offer breakthrough solutions. The numerous challenges introduced by natural orifice approaches require a radical shift in the conception of new technologies in order to make this emerging operative access safe and reproducible. The convergence of several enabling technologies in the field of miniaturization, communication and micro-mechatronics brings the possibility to realize on a large scale the revolutionary concept of miniature in vivo co-operative robots. These robots provide vision and task assistance without the constraints of the entry incision and have been shown in experimental settings to possess many qualities that could be ideal to partner with Natural Orifice Surgery. This article explores the current status of microrobotics as well as presents potential future scenarios of their applications in NOTES.

Using Mechanical Turk for research on cancer survivors.

PubMed

Arch, Joanna J; Carr, Alaina L

2017-10-01

The successful recruitment and study of cancer survivors within psycho-oncology research can be challenging, time-consuming, and expensive, particularly for key subgroups such as young adult cancer survivors. Online crowdsourcing platforms offer a potential solution that has not yet been investigated with regard to cancer populations. The current study assessed the presence of cancer survivors on Amazon's Mechanical Turk (MTurk) and the feasibility of using MTurk as an efficient, cost-effective, and reliable psycho-oncology recruitment and research platform. During a <4-month period, cancer survivors living in the United States were recruited on MTurk to complete two assessments, spaced 1 week apart, relating to psychosocial and cancer-related functioning. The reliability and validity of responses were investigated. Within a <4-month period, 464 self-identified cancer survivors on MTurk consented to and completed an online assessment. The vast majority (79.09%) provided reliable and valid study data according to multiple indices. The sample was highly diverse in terms of U.S. geography, socioeconomic status, and cancer type, and reflected a particularly strong presence of distressed and young adult cancer survivors (median age = 36 years). A majority of participants (58.19%) responded to a second survey sent one week later. Online crowdsourcing represents a feasible, efficient, and cost-effective recruitment and research platform for cancer survivors, particularly for young adult cancer survivors and those with significant distress. We discuss remaining challenges and future recommendations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

NIH research funding and early career physician scientists: continuing challenges in the 21st century

PubMed Central

Garrison, Howard H.; Deschamps, Anne M.

2014-01-01

Physician scientists (researchers with either M.D. or M.D.-Ph.D. degrees) have the unique potential to combine clinical perspectives with scientific insight, and their participation in biomedical research has long been an important topic for policymakers and educators. Given the recent changes in the research environment, an update and extension of earlier studies of this population was needed. Our findings show that physician scientists are less likely to take a major role in biomedical research than they were in the past. The number of physician scientists receiving postdoctoral research training and career development awards is at an all-time low. Physician scientists today, on average, receive their first major research award (R01 equivalent) at a later age than in the 1980s. The number of first-time R01-equivalent awards to physicians is at the same level as it was 30 yr ago, but physicians now represent a smaller percentage of the grant recipients. The long-term decline in the number of physicians entering research careers was temporarily halted during the period of substantial U.S. National Institutes of Health (NIH) budget growth (1998–2003). These gains are lost, however, in the subsequent years when NIH budgets failed to keep pace with rising costs.— Garrison, H. H., Deschamps, A. M. NIH research funding and early career physician scientists: continuing challenges in the 21st century. PMID:24297696

Exploration in petroleum development in Oman: Getting a kick into the creaming curve

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

Knox, G.J.

1993-09-01

Petroleum Development Oman (PDO) currently explores an 80,000 mi[sup 2] concession area. Major discoveries were made in the early 1960s in north Oman and in south Oman in the 1970s. However, in the middle to late 1980s, discovery sizes decreased, consistent with classical creaming curves, particularly as exploration concentrated on areas around the hydrocarbon fairways. With a flattening creaming curve, the outlook did not look rosy. PDO faced the question, [open quotes]Does this curve represent the future or could new ideas, a change in approach, or application of newer technologies give an upward kick to the creaming curve [close quotes]more » A major strategy review took place in which the potential of all plays was reviewed. Prospects were place into frontier, conventional, and exploratory appraisal types. String time was allocated over a five-year period on a basis of play testing for frontier plays and a steady realization of conventional and exploratory appraisal drilling as partial fulfillment of the annual exploration reserves replenishment target. Initial results are promising, and specific challenges including new plays, one unique to Oman, have been defined beyond the aims of the original strategy. Resolution of these challenges will lead to delineation of new hydrocarbon resources in Oman. At the same time, technological advances such as slim-hole drilling and extensive three-dimensional seismic, in concert with work-station interpretation, are being used, in order to minimize costs and increase the success ratio.« less

Child Care Challenge. A Report of the Select Committee on Children, Youth, and Families. House of Representatives, One Hundred Second Congress, Second Session. Committee Print.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Select Committee on Children, Youth, and Families.

In 1991, the Select Committee on Children, Youth, and Families challenged members of the House of Representatives to seek out innovative, high quality child care programs in their districts. The programs were to serve as models for states and local jurisdictions or for employers and others in the public and private sectors who were trying to…

75 FR 35766 - Establishment of the Renewable Energy and Energy Efficiency Advisory Committee and Solicitation...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-23

.... No member may represent a company that is majority owned or controlled by a foreign government entity... member may represent a company that is majority owned or controlled by a foreign government entity or... committee of U.S. citizens who will represent U.S. companies in the renewable energy and energy efficiency...

Feasibility and Acceptability of Implementing the Integrated Care Plan for the Dying in the Indian Setting: Survey of Perspectives of Indian Palliative Care Providers.

PubMed

Salins, Naveen; Johnson, Jeremy; Macaden, Stanley

2017-01-01

Capacity to provide end-of-life care in India is scored as 0.6/100, and very few people in India have access to palliative and end-of-life care. Lack of end-of-life care provision in India has led to a significant number of people receiving inappropriate medical treatment at the end of life, with no access to pain and symptom control and high treatment costs. The International Collaborative for the Best Care for the Dying Person is an initiative that offers the opportunity to apply international evidence on the key factors required to provide best care for the dying in the Indian context. The aim of this study is to ascertain the perceptions of Indian palliative care providers regarding the feasibility and acceptability of implementing the international program in the Indian setting. Thirty participants from 16 palliative care centers who had participated in the foundation course of the International Collaborative for Best Care for the Dying Person were purposively chosen for the study. All participants were asked to complete the survey questionnaire that had both open- and close-ended questions. Twenty-three participants completed this survey. The majority of items in the international program were considered relevant, representative of end-of-life care and acceptable in Indian setting. However, participants felt that the concept of the multidisciplinary team (MDT) being responsible for recognizing death may not be possible in the existing Indian setting and a senior doctor may not always be available to document a MDT decision. Some participants felt that in the Indian setting, it was not always possible to communicate about the dying process and make patient aware of the same. A small number of participants felt that using leaflets for communicating end-of-life care process may not be always possible due to logistic reasons and cost. Six participants felt that giving the dying person the opportunity to discuss their wishes, feelings, faith, beliefs, and values may not be possible, representative, and not applicable in Indian setting. The majority of participants felt that using equipment such as a syringe driver for continuous infusion is relevant ( n = 16) and representative ( n = 13) of end-of-life care, however most thought that it could be challenging to apply in an Indian setting ( n = 17), including concerns about lack of familiarity and knowledge and applicability in home care settings. Six participants had reservations regarding the limitation of life-sustaining treatment and felt that discussion and review of cardiopulmonary resuscitation should happen prior to patients entering their end-of-life phase. While most participants thought relevance, representation, and applicability of assessing skin integrity as important, a few participants felt this assessment challenging, especially in home setting, and recommended Braden scale to be used instead of Waterlow for assessing skin integrity. Most participants agreed on the importance of assisted hydration and nutrition; however, again a minority highlighted challenges in this area. Five participants felt that they would sometimes continue hydration under duress from a patient's family. Participants agreed unanimously on the relevance and representation of recording of physical symptoms by MDT-initial and ongoing-with a few participants indicating that frequent observations recommended in the care plan may not be feasible in home care setting. The majority also agreed on the relevance, representation ( n = 21), and applicability ( n = 18) of providing written information about after-death care, with a small number indicating challenges in the Indian setting, for example, very few unit currently having this information available ( n = 2). Notifying general practitioners, primary care physicians, and other appropriate services on patients' death may not be easily applicable in the Indian setting. The survey of palliative care providers about the feasibility and acceptability of integrated care plan at end of life has shown that the international program is relevant, representative of end-of-life care, and acceptable in Indian setting. As would be expected, a number of items need careful consideration and appropriate modification to ensure relevance, representation, and applicability to Indian sociocultural context. The results also suggest that palliative care providers need additional training for the implementation of some of the items in the development of an India-specific document and supporting quality improvement program.

Feasibility and Acceptability of Implementing the Integrated Care Plan for the Dying in the Indian Setting: Survey of Perspectives of Indian Palliative Care Providers

PubMed Central

Salins, Naveen; Johnson, Jeremy; Macaden, Stanley

2017-01-01

Introduction: Capacity to provide end-of-life care in India is scored as 0.6/100, and very few people in India have access to palliative and end-of-life care. Lack of end-of-life care provision in India has led to a significant number of people receiving inappropriate medical treatment at the end of life, with no access to pain and symptom control and high treatment costs. The International Collaborative for the Best Care for the Dying Person is an initiative that offers the opportunity to apply international evidence on the key factors required to provide best care for the dying in the Indian context. The aim of this study is to ascertain the perceptions of Indian palliative care providers regarding the feasibility and acceptability of implementing the international program in the Indian setting. Methods: Thirty participants from 16 palliative care centers who had participated in the foundation course of the International Collaborative for Best Care for the Dying Person were purposively chosen for the study. All participants were asked to complete the survey questionnaire that had both open- and close-ended questions. Results: Twenty-three participants completed this survey. The majority of items in the international program were considered relevant, representative of end-of-life care and acceptable in Indian setting. However, participants felt that the concept of the multidisciplinary team (MDT) being responsible for recognizing death may not be possible in the existing Indian setting and a senior doctor may not always be available to document a MDT decision. Some participants felt that in the Indian setting, it was not always possible to communicate about the dying process and make patient aware of the same. A small number of participants felt that using leaflets for communicating end-of-life care process may not be always possible due to logistic reasons and cost. Six participants felt that giving the dying person the opportunity to discuss their wishes, feelings, faith, beliefs, and values may not be possible, representative, and not applicable in Indian setting. The majority of participants felt that using equipment such as a syringe driver for continuous infusion is relevant (n = 16) and representative (n = 13) of end-of-life care, however most thought that it could be challenging to apply in an Indian setting (n = 17), including concerns about lack of familiarity and knowledge and applicability in home care settings. Six participants had reservations regarding the limitation of life-sustaining treatment and felt that discussion and review of cardiopulmonary resuscitation should happen prior to patients entering their end-of-life phase. While most participants thought relevance, representation, and applicability of assessing skin integrity as important, a few participants felt this assessment challenging, especially in home setting, and recommended Braden scale to be used instead of Waterlow for assessing skin integrity. Most participants agreed on the importance of assisted hydration and nutrition; however, again a minority highlighted challenges in this area. Five participants felt that they would sometimes continue hydration under duress from a patient's family. Participants agreed unanimously on the relevance and representation of recording of physical symptoms by MDT–initial and ongoing–with a few participants indicating that frequent observations recommended in the care plan may not be feasible in home care setting. The majority also agreed on the relevance, representation (n = 21), and applicability (n = 18) of providing written information about after-death care, with a small number indicating challenges in the Indian setting, for example, very few unit currently having this information available (n = 2). Notifying general practitioners, primary care physicians, and other appropriate services on patients' death may not be easily applicable in the Indian setting. Conclusions: The survey of palliative care providers about the feasibility and acceptability of integrated care plan at end of life has shown that the international program is relevant, representative of end-of-life care, and acceptable in Indian setting. As would be expected, a number of items need careful consideration and appropriate modification to ensure relevance, representation, and applicability to Indian sociocultural context. The results also suggest that palliative care providers need additional training for the implementation of some of the items in the development of an India-specific document and supporting quality improvement program. PMID:28216856

A highly printable and biocompatible hydrogel composite for direct printing of soft and perfusable vasculature-like structures.

PubMed

Suntornnond, Ratima; Tan, Edgar Yong Sheng; An, Jia; Chua, Chee Kai

2017-12-04

Vascularization is one major obstacle in bioprinting and tissue engineering. In order to create thick tissues or organs that can function like original body parts, the presence of a perfusable vascular system is essential. However, it is challenging to bioprint a hydrogel-based three-dimensional vasculature-like structure in a single step. In this paper, we report a new hydrogel-based composite that offers impressive printability, shape integrity, and biocompatibility for 3D bioprinting of a perfusable complex vasculature-like structure. The hydrogel composite can be used on a non-liquid platform and is printable at human body temperature. Moreover, the hydrogel composite supports both cell proliferation and cell differentiation. Our results represent a potentially new vascularization strategy for 3D bioprinting and tissue engineering.

The Genetic Challenges and Opportunities in Advanced Heart Failure

PubMed Central

Hannah-Shmouni, Fady; Seidelmann, Sara B.; Sirrs, Sandra; Mani, Arya; Jacoby, Daniel

2017-01-01

The causes of heart failure are diverse. Inherited causes represent an important clinical entity and can be divided into 2 major categories: familial and metabolic cardiomyopathies. The distinct features that might be present in early disease states can become broadly overlapping with other diseases, such as in the case of inherited cardiomyopathies (ie, familial hypertrophic cardiomyopathy or mitochondrial diseases). In this review article, we focus on genetic issues related to advanced heart failure. Because of the emerging importance of this topic and its breadth, we sought to focus our discussion on the known genetic forms of heart failure syndromes, genetic testing, and newer data on pharmacogenetics and therapeutics in the treatment of heart failure, to primarily encourage clinicians to place a priority on the diagnosis and treatment of these potentially treatable conditions. PMID:26518444

Psychological first aid: a consensus-derived, empirically supported, competency-based training model.

PubMed

McCabe, O Lee; Everly, George S; Brown, Lisa M; Wendelboe, Aaron M; Abd Hamid, Nor Hashidah; Tallchief, Vicki L; Links, Jonathan M

2014-04-01

Surges in demand for professional mental health services occasioned by disasters represent a major public health challenge. To build response capacity, numerous psychological first aid (PFA) training models for professional and lay audiences have been developed that, although often concurring on broad intervention aims, have not systematically addressed pedagogical elements necessary for optimal learning or teaching. We describe a competency-based model of PFA training developed under the auspices of the Centers for Disease Control and Prevention and the Association of Schools of Public Health. We explain the approach used for developing and refining the competency set and summarize the observable knowledge, skills, and attitudes underlying the 6 core competency domains. We discuss the strategies for model dissemination, validation, and adoption in professional and lay communities.

Psychological First Aid: A Consensus-Derived, Empirically Supported, Competency-Based Training Model

PubMed Central

Everly, George S.; Brown, Lisa M.; Wendelboe, Aaron M.; Abd Hamid, Nor Hashidah; Tallchief, Vicki L.; Links, Jonathan M.

2014-01-01

Surges in demand for professional mental health services occasioned by disasters represent a major public health challenge. To build response capacity, numerous psychological first aid (PFA) training models for professional and lay audiences have been developed that, although often concurring on broad intervention aims, have not systematically addressed pedagogical elements necessary for optimal learning or teaching. We describe a competency-based model of PFA training developed under the auspices of the Centers for Disease Control and Prevention and the Association of Schools of Public Health. We explain the approach used for developing and refining the competency set and summarize the observable knowledge, skills, and attitudes underlying the 6 core competency domains. We discuss the strategies for model dissemination, validation, and adoption in professional and lay communities. PMID:23865656

3D Texture Features Mining for MRI Brain Tumor Identification

NASA Astrophysics Data System (ADS)

Rahim, Mohd Shafry Mohd; Saba, Tanzila; Nayer, Fatima; Syed, Afraz Zahra

2014-03-01

Medical image segmentation is a process to extract region of interest and to divide an image into its individual meaningful, homogeneous components. Actually, these components will have a strong relationship with the objects of interest in an image. For computer-aided diagnosis and therapy process, medical image segmentation is an initial mandatory step. Medical image segmentation is a sophisticated and challenging task because of the sophisticated nature of the medical images. Indeed, successful medical image analysis heavily dependent on the segmentation accuracy. Texture is one of the major features to identify region of interests in an image or to classify an object. 2D textures features yields poor classification results. Hence, this paper represents 3D features extraction using texture analysis and SVM as segmentation technique in the testing methodologies.

Assessment of cortical auditory evoked potentials in children with specific language impairment.

PubMed

Włodarczyk, Elżbieta; Szkiełkowska, Agata; Pilka, Adam; Skarżyński, Henryk

2018-02-28

The proper course of speech development heavily influences the cognitive and personal development of children. It is a condition for achieving preschool and school successes - it facilitates socializing and expressing feelings and needs. Impairment of language and its development in children represents a major diagnostic and therapeutic challenge for physicians and therapists. Early diagnosis of coexisting deficits and starting the therapy influence the therapeutic success. One of the basic diagnostic tests for children suffering from specific language impairment (SLI) is audiometry, thus far referred to as a hearing test. Auditory processing is just as important as a proper hearing threshold. Therefore, diagnosis of central auditory disorder may be a valuable supplementation of diagnosis of language impairment. Early diagnosis and implementation of appropriate treatment may contribute to an effective language therapy.

Progress and challenges in the prevention and control of nonalcoholic fatty liver disease.

PubMed

Cai, Jingjing; Zhang, Xiao-Jing; Li, Hongliang

2018-05-30

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism-related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health-care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier. This review summarizes the characteristics and prevalence of the disease and the status of our understanding of its mechanisms and potential therapeutic targets. © 2018 Wiley Periodicals, Inc.

Evaluation of bacteriophage therapy to control Clostridium difficile and toxin production in an in vitro human colon model system.

PubMed

Meader, Emma; Mayer, Melinda J; Steverding, Dietmar; Carding, Simon R; Narbad, Arjan

2013-08-01

Clostridium difficile is a leading cause of hospital-acquired diarrhoea and represents a major challenge for healthcare providers. Due to the decreasing efficacy and associated problems of antibiotic therapy there is a need for synergistic and alternative treatments. In this study we investigated the use of a specific bacteriophage, ΦCD27, in a human colon model of C. difficile infection. Our findings demonstrate a significant reduction in the burden of C. difficile cells and toxin production with phage treatment relative to an untreated control, with no detrimental effect on commensal bacterial populations. The results demonstrate the potential of phage therapy, and highlight the limitations of using phages that have lysogenic capacity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact Of Resolving Submesoscale Features On Modeling The Gulf Stream System

NASA Astrophysics Data System (ADS)

Chassignet, E.; Xu, X.

2016-02-01

Despite being one the best-known circulation pattern of the world ocean, the representation of the Gulf Stream, especially its energetic extension east of the New England Seamounts Chains in the western North Atlantic Ocean, has been a major challenge for ocean general circulation models even at eddy-rich resolutions. Here we show that, for the first time, a simulation of the North Atlantic circulation at 1/50° resolution realistically represents the narrow, energetic jet near 55°W when compared to observations, whereas similarly configured simulations at 1/25° and 1/12° resolution do not. This result highlights the importance of submesoscale features in driving the energetic Gulf Stream extension in the western North Atlantic. The results are discussed in terms of mesoscale and submesoscale energy power spectra.

Population-level genomics identifies the emergence and global spread of a human transmissible multidrug-resistant nontuberculous mycobacterium

PubMed Central

Rodriguez-Rincon, Daniela; Everall, Isobel; Brown, Karen P; Moreno, Pablo; Verma, Deepshikha; Hill, Emily; Drijkoningen, Judith; Gilligan, Peter; Esther, Charles R; Noone, Peadar G; Giddings, Olivia; Bell, Scott C.; Thomson, Rachel; Wainwright, Claire E.; Coulter, Chris; Pandey, Sushil; Wood, Michelle E; Stockwell, Rebecca E; Ramsay, Kay A; Sherrard, Laura J; Kidd, Timothy J; Jabbour, Nassib; Johnson, Graham R; Knibbs, Luke D; Morawska, Lidia; Sly, Peter D; Jones, Andrew; Bilton, Diana; Laurenson, Ian; Ruddy, Michael; Bourke, Stephen; Bowler, Ian CJW; Chapman, Stephen J; Clayton, Andrew; Cullen, Mairi; Daniels, Thomas; Dempsey, Owen; Denton, Miles; Desai, Maya; Drew, Richard J; Edenborough, Frank; Evans, Jason; Folb, Jonathan; Humphrey, Helen; Isalska, Barbara; Jensen-Fangel, Søren; Jönsson, Bodil; Jones, Andrew M.; Katzenstein, Terese L; Lillebaek, Troels; MacGregor, Gordon; Mayell, Sarah; Millar, Michael; Modha, Deborah; Nash, Edward F; O’Brien, Christopher; O’Brien, Deirdre; Ohri, Chandra; Pao, Caroline S; Peckham, Daniel; Perrin, Felicity; Perry, Audrey; Pressler, Tania; Prtak, Laura; Qvist, Tavs; Robb, Ali; Rodgers, Helen; Schaffer, Kirsten; Shafi, Nadia; van Ingen, Jakko; Walshaw, Martin; Watson, Danie; West, Noreen; Whitehouse, Joanna; Haworth, Charles S; Harris, Simon R; Ordway, Diane; Parkhill, Julian; Floto, R. Andres

2016-01-01

Lung infections with Mycobacterium abscessus, a species of multidrug resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF) where they accelerate inflammatory lung damage leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge. PMID:27846606

What can Natural Language Processing do for Clinical Decision Support?

PubMed Central

Demner-Fushman, Dina; Chapman, Wendy W.; McDonald, Clement J.

2009-01-01

Computerized Clinical Decision Support (CDS) aims to aid decision making of health care providers and the public by providing easily accessible health-related information at the point and time it is needed. Natural Language Processing (NLP) is instrumental in using free-text information to drive CDS, representing clinical knowledge and CDS interventions in standardized formats, and leveraging clinical narrative. The early innovative NLP research of clinical narrative was followed by a period of stable research conducted at the major clinical centers and a shift of mainstream interest to biomedical NLP. This review primarily focuses on the recently renewed interest in development of fundamental NLP methods and advances in the NLP systems for CDS. The current solutions to challenges posed by distinct sublanguages, intended user groups, and support goals are discussed. PMID:19683066

Using Digital Health Technology to Better Generate Evidence and Deliver Evidence-Based Care.

PubMed

Sharma, Abhinav; Harrington, Robert A; McClellan, Mark B; Turakhia, Mintu P; Eapen, Zubin J; Steinhubl, Steven; Mault, James R; Majmudar, Maulik D; Roessig, Lothar; Chandross, Karen J; Green, Eric M; Patel, Bakul; Hamer, Andrew; Olgin, Jeffrey; Rumsfeld, John S; Roe, Matthew T; Peterson, Eric D

2018-06-12

As we enter the information age of health care, digital health technologies offer significant opportunities to optimize both clinical care delivery and clinical research. Despite their potential, the use of such information technologies in clinical care and research faces major data quality, privacy, and regulatory concerns. In hopes of addressing both the promise and challenges facing digital health technologies in the transformation of health care, we convened a think tank meeting with academic, industry, and regulatory representatives in December 2016 in Washington, DC. In this paper, we summarize the proceedings of the think tank meeting and aim to delineate a framework for appropriately using digital health technologies in healthcare delivery and research. Copyright © 2018 American College of Cardiology Foundation. All rights reserved.

Induction of virus resistance by exogenous application of double-stranded RNA.

PubMed

Mitter, Neena; Worrall, Elizabeth A; Robinson, Karl E; Xu, Zhi Ping; Carroll, Bernard J

2017-10-01

Exogenous application of double-stranded RNA (dsRNA) for virus resistance in plants represents a very attractive alternative to virus resistant transgenic crops or pesticides targeting virus vectors. However, the instability of dsRNA sprayed onto plants is a major challenge as spraying naked dsRNA onto plants provides protection against homologous viruses for only 5 days. Innovative approaches, such as the use of nanoparticles as carriers of dsRNA for improved stability and sustained release, are emerging as key disruptive technologies. Knowledge is still limited about the mechanism of entry, transport and processing of exogenously applied dsRNA in plants. Cost of dsRNA and regulatory framework will be key influencers towards practical adoption of this technology. Copyright © 2017 Elsevier B.V. All rights reserved.

["Jaques-Dalcroze eurhythmics" improves gait and prevents falls in the elderly].

PubMed

Trombetti, Andrea; Hars, Mélany; Herrmann, François; Kressig, Reto; Ferrari, Serge; Rizzoli, René

2011-06-15

Given the significant health and socioeconomic consequences of falls, to develop and promote effective falls prevention strategies among older adults represents a major issue. Jaques-Dalcroze eurhythmics is a music education program through movement method developed in Geneva, Switzerland, in the early 20th century. This new exercise form, adapted for elderly people, features various multitask exercises performed to the rhythm of improvised piano music and mainly challenge gait and balance, but also memory, attention and coordination. We report here the results of a randomized controlled trial conducted in Geneva showing that Jaques-Dalcroze eurythmics practice can improve gait performance under single and dual-task conditions, and balance, as well as reduce both rate of falls and the risk of falling in at-risk elderly community-dwellers.

Hemispheric aerosol vertical profiles: anthropogenic impacts on optical depth and cloud nuclei.

PubMed

Clarke, Antony; Kapustin, Vladimir

2010-09-17

Understanding the effect of anthropogenic combustion upon aerosol optical depth (AOD), clouds, and their radiative forcing requires regionally representative aerosol profiles. In this work, we examine more than 1000 vertical profiles from 11 major airborne campaigns in the Pacific hemisphere and confirm that regional enhancements in aerosol light scattering, mass, and number are associated with carbon monoxide from combustion and can exceed values in unperturbed regions by more than one order of magnitude. Related regional increases in a proxy for cloud condensation nuclei (CCN) and AOD imply that direct and indirect aerosol radiative effects are coupled issues linked globally to aged combustion. These profiles constrain the influence of combustion on regional AOD and CCN suitable for challenging climate model performance and informing satellite retrievals.

Programming Chemical Reaction Networks Using Intramolecular Conformational Motions of DNA.

PubMed

Lai, Wei; Ren, Lei; Tang, Qian; Qu, Xiangmeng; Li, Jiang; Wang, Lihua; Li, Li; Fan, Chunhai; Pei, Hao

2018-06-22

The programmable regulation of chemical reaction networks (CRNs) represents a major challenge toward the development of complex molecular devices performing sophisticated motions and functions. Nevertheless, regulation of artificial CRNs is generally energy- and time-intensive as compared to natural regulation. Inspired by allosteric regulation in biological CRNs, we herein develop an intramolecular conformational motion strategy (InCMS) for programmable regulation of DNA CRNs. We design a DNA switch as the regulatory element to program the distance between the toehold and branch migration domain. The presence of multiple conformational transitions leads to wide-range kinetic regulation spanning over 4 orders of magnitude. Furthermore, the process of energy-cost-free strand exchange accompanied by conformational change discriminates single base mismatches. Our strategy thus provides a simple yet effective approach for dynamic programming of complex CRNs.

Implementation of diverse tree hydraulics in a land surface model

NASA Astrophysics Data System (ADS)

Wolf, A.; Shevliakova, E.; Malyshev, S.; Weng, E.; Pacala, S. W.

2013-12-01

Increasing attention has been devoted to the occurence of drought kill in forests worldwide. These mortality events are significant disruptions to the terrestrial carbon cycle, but the mechanisms required to represent drought kill are not represented in terrestrial carbon cycle models. In part, this is due to the challenge of representing the diversity of hydraulic strategies, which include stomatal sensitivity to water deficit and woody tissue vulnerability to cavitation at low water potential. In part, this is due to the challenge of representing this boundary value problem numerically, because the hydraulic components determine water potential at the leaf, but the stomatal conductance on the leaf also determines the hydraulic gradients within the plant. This poster will describe the development of a land surface model parameterization of diverse tree hydraulic strategies.

Cyber security challenges in Smart Cities: Safety, security and privacy

PubMed Central

Elmaghraby, Adel S.; Losavio, Michael M.

2014-01-01

The world is experiencing an evolution of Smart Cities. These emerge from innovations in information technology that, while they create new economic and social opportunities, pose challenges to our security and expectations of privacy. Humans are already interconnected via smart phones and gadgets. Smart energy meters, security devices and smart appliances are being used in many cities. Homes, cars, public venues and other social systems are now on their path to the full connectivity known as the “Internet of Things.” Standards are evolving for all of these potentially connected systems. They will lead to unprecedented improvements in the quality of life. To benefit from them, city infrastructures and services are changing with new interconnected systems for monitoring, control and automation. Intelligent transportation, public and private, will access a web of interconnected data from GPS location to weather and traffic updates. Integrated systems will aid public safety, emergency responders and in disaster recovery. We examine two important and entangled challenges: security and privacy. Security includes illegal access to information and attacks causing physical disruptions in service availability. As digital citizens are more and more instrumented with data available about their location and activities, privacy seems to disappear. Privacy protecting systems that gather data and trigger emergency response when needed are technological challenges that go hand-in-hand with the continuous security challenges. Their implementation is essential for a Smart City in which we would wish to live. We also present a model representing the interactions between person, servers and things. Those are the major element in the Smart City and their interactions are what we need to protect. PMID:25685517

The Future of Water Security in Metropolitan Region of Sao Paulo Through Different Climate Scenarios

NASA Astrophysics Data System (ADS)

Gesualdo, G. C.; Oliveira, P. T. S.; Rodrigues, D. B. B.

2017-12-01

Achieving a balance between water availability and demand is one of the most pressing environmental challenges in the twenty-first century. This challenge is exacerbated by, climate change, which has already affected the water balance of landscapes globally by intensifying runoff, reducing snowpacks, and shifting precipitation regimes. Understanding these changes is crucial to identifying future water availability and developing sustainable management plans, especially in developing countries. Here, we address the developing country water balance challenge by assessing the influence of climate change on the water availability in the Jaguari basin, Southeastern Brazil. The Jaguari basin is one of the main sources of freshwater for 9 million people in the Metropolitan Region of São Paulo. This region represents about 7% of the Brazil's Gross Domestic Product. The critical importance of the water balance challenge in this area has been highlighted recently when a major drought in southeastern Brazil revealed the vulnerability of current water management systems. Still today, the per capita water availability in the region remains severely limited. To help address this water balance challenge, we use a modeling approach to predict future water vulnerabilities of this region under different climate scenarios. Here, we calibrated and validated a lumped conceptual model using HYMOD to evaluate future scenarios using downscaled climate models resulting from HadGEM2-ES and MIROC5 GCMs forced by RCP4.5 and RCP8.5 scenarios. We also present future directions which include bias correction from long-term weather station data and an empirical uncertainty assessment. Our results provide an important overview of climate change impacts on streamflow and future water availability in the Jaguari basin, which can be used to guide the basin`s water security plans and strategies.

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

Clinical Implications of ESR1 Mutations in Hormone Receptor-Positive Advanced Breast Cancer

PubMed Central

Reinert, Tomas; Saad, Everardo D.; Barrios, Carlos H.; Bines, José

2017-01-01

Hormone receptor-positive breast cancer is the most frequent breast cancer subtype. Endocrine therapy (ET) targeting the estrogen receptor (ER) pathway represents the main initial therapeutic approach. The major strategies include estrogen deprivation and the use of selective estrogen modulators or degraders, which show efficacy in the management of metastatic and early-stage disease. However, clinical resistance associated with progression of disease remains a significant therapeutic challenge. Mutations of the ESR1 gene, which encodes the ER, have been increasingly recognized as an important mechanism of ET resistance, with a prevalence that ranges from 11 to 39%. The majority of these mutations are located within the ligand-binding domain and result in an estrogen-independent constitutive activation of the ER and, therefore, resistance to estrogen deprivation therapy such as aromatase inhibition. ESR1 mutations, most often detected from liquid biopsies, have been consistently associated with a worse outcome and are being currently evaluated as a potential biomarker to guide therapeutic decisions. At the same time, targeted therapy directed to ESR1-mutated clones is an appealing concept with preclinical and clinical work in progress. PMID:28361033

The Preventive Control of Zoonotic Visceral Leishmaniasis: Efficacy and Economic Evaluation

PubMed Central

Wu, Jianhong; Massad, Eduardo

2017-01-01

Zoonotic Visceral Leishmaniasis (ZVL) is one of the world's deadliest and neglected infectious diseases, according to World Health Organization. This disease is one of major human and veterinary medical significance. The sandfly and the reservoir in urban areas remain among the major challenges for the control activities. In this paper, we evaluated five control strategies (positive dog elimination, insecticide impregnated dog collar, dog vaccination, dog treatment, and sandfly population control), considering disease control results and cost-effectiveness. We elaborated a mathematical model based on a set of differential equations in which three populations were represented (human, dog, and sandfly). Humans and dogs were divided into susceptible, latent, clinically ill, and recovery categories. Sandflies were divided into noninfected, infected, and infective. As the main conclusions, the insecticide impregnated dog collar was the strategy that presented the best combination between disease control and cost-effectiveness. But, depending on the population target, the control results and cost-effectiveness of each strategy may differ. More and detailed studies are needed, specially one which optimizes the control considering more than one strategy in activity. PMID:28588642

Patient-centered medical home cyberinfrastructure current and future landscape.

PubMed

Finkelstein, Joseph; Barr, Michael S; Kothari, Pranav P; Nace, David K; Quinn, Matthew

2011-05-01

The patient-centered medical home (PCMH) is an approach that evolved from the understanding that a well-organized, proactive clinical team working in a tandem with well-informed patients is better able to address the preventive and disease management needs in a guideline-concordant manner. This approach represents a fundamental shift from episodic acute care models and has become an integral part of health reform supported on a federal level. The major aspects of PCMH, especially pertinent to its information infrastructure, have been discussed by an expert panel organized by the Agency for Healthcare Research and Quality at the Informatics for Consumer Health Summit. The goal of this article is to summarize the panel discussions along the four major domains presented at the summit: (1) PCMH as an Evolving Model of Healthcare Delivery; (2) Health Information Technology (HIT) Applications to Support the PCMH; (3) Current HIT Landscape of PCMH: Challenges and Opportunities; and (4) Future HIT Landscape of PCMH: Federal Initiatives on Health Informatics, Legislation, and Standardization. Copyright © 2011 American Journal of Preventive Medicine. All rights reserved.

Co-operation and conflict in a hospital: interprofessional differences in perception and management of conflicts.

PubMed

Skjørshammer, M

2001-02-01

This article presents a case study of a Norwegian hospital, analysing how health professionals manage conflicts related to work co-operation. Altogether, 29 health professionals working in the hospital were interviewed, and data was analysed according to a grounded theory approach. When in conflict, health professionals seem to use three major approaches to handling the situation: avoidance, forcing and negotiation, and usually in that order. Avoidance behaviour or suppression is the most common reaction to an emerging conflict. If the use of power does not re-establish a balance between the participants, one negotiates. These conflict styles seem to be determined by two major factors: the perceived interdependence between parties and the perceived urgency of doing something about the situation. Nurses and physicians in particular seem to differ considerably in their perception of what is a conflict and when to do something about it. Such differences in perceptions and the extensive use of avoidance represent important challenges to managers and clinical leaders when it comes to advancing interprofessional co-operation.

Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity

PubMed Central

Palm, Noah W.; Rosenstein, Rachel K.; Yu, Shuang; Schenten, Dominik; Florsheim, Esther; Medzhitov, Ruslan

2013-01-01

SUMMARY Venoms consist of toxic components that are delivered to their victims via bites or stings. Venoms also represent a major class of allergens in humans. Phospholipase A2 (PLA2) is a conserved component of venoms from multiple species and is the major allergen in bee venom. Here we examined how bee venom PLA2 is sensed by the innate immune system and induces a type 2 immune response in mice. We found that bee venom PLA2 induced a T helper type 2 (Th2) cell-type response and group 2 innate lymphoid cell activation via the enzymatic cleavage of membrane phospholipids and release of interleukin-33. Furthermore, we showed that the IgE response to PLA2 could protect mice from future challenge with a near-lethal dose of PLA2. These data suggest that the innate immune system can detect the activity of a conserved component of venoms and induce a protective immune response against a venom toxin. PMID:24210353

The Preventive Control of Zoonotic Visceral Leishmaniasis: Efficacy and Economic Evaluation.

PubMed

Shimozako, Helio Junji; Wu, Jianhong; Massad, Eduardo

2017-01-01

Zoonotic Visceral Leishmaniasis (ZVL) is one of the world's deadliest and neglected infectious diseases, according to World Health Organization. This disease is one of major human and veterinary medical significance. The sandfly and the reservoir in urban areas remain among the major challenges for the control activities. In this paper, we evaluated five control strategies (positive dog elimination, insecticide impregnated dog collar, dog vaccination, dog treatment, and sandfly population control), considering disease control results and cost-effectiveness. We elaborated a mathematical model based on a set of differential equations in which three populations were represented (human, dog, and sandfly). Humans and dogs were divided into susceptible, latent, clinically ill, and recovery categories. Sandflies were divided into noninfected, infected, and infective. As the main conclusions, the insecticide impregnated dog collar was the strategy that presented the best combination between disease control and cost-effectiveness. But, depending on the population target, the control results and cost-effectiveness of each strategy may differ. More and detailed studies are needed, specially one which optimizes the control considering more than one strategy in activity.

The "BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons" (BIOSPHERE) study: Rationale, design and methods.

PubMed

Calvani, Riccardo; Picca, Anna; Marini, Federico; Biancolillo, Alessandra; Cesari, Matteo; Pesce, Vito; Lezza, Angela Maria Serena; Bossola, Maurizio; Leeuwenburgh, Christiaan; Bernabei, Roberto; Landi, Francesco; Marzetti, Emanuele

2018-05-10

Sarcopenia, the progressive and generalised loss of muscle mass and strength/function, is a major health issue in older adults given its high prevalence and burdensome clinical implications. Over the years, this condition has been endorsed as a marker for discriminating biological from chronological age. However, the absence of a unified operational definition has hampered its full appreciation by healthcare providers, researchers and policy-makers. In addition to this unsolved debate, the complexity of musculoskeletal ageing represents a major challenge to the identification of clinically meaningful biomarkers. Here, we illustrate the advantages of biomarker discovery procedures in muscle ageing based on multivariate methodologies as an alternative approach to traditional single-marker strategies. The rationale, design and methods of the "BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons" (BIOSPHERE) study are described as an application of a multi-marker strategy for the development of biomarkers for the newly operationalised Physical Frailty & Sarcopenia condition. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

MicroRNAs Change the Landscape of Cancer Resistance.

PubMed

Zhu, Jun; Zhu, Wei; Wu, Wei

2018-01-01

One of the major challenges in the cancer treatment is the development of drug resistance. It represents a major obstacle to curing cancer with constrained efficacy of both conventional chemotherapy and targeted therapies, even recent immune checkpoint blockade therapy. Deciphering the mechanisms of resistance is critical to further understanding the multifactorial pathways involved, and developing more specific targeted treatments. To date, numerous studies have reported the potential role of microRNAs (miRNAs) in the resistance to various cancer treatments. MicroRNAs are a family of small noncoding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing translational repression or mRNA degradation. More than 1200 validated human miRNAs have been identified in human genome. While one miRNA can regulate hundreds of targets, a single target can also be affected by multiple miRNAs. Evidence suggests that dysregulation of specific miRNAs may be involved in the acquisition of resistance, thereby modulating the sensitivity of cancer cells to treatment. Therefore, manipulation of miRNAs may be an attractive strategy for more effective individualized therapies through reprograming resistant network in cancer cells.

A review of thermoregulation and physiological performance in reptiles: what is the role of phenotypic flexibility?

PubMed

Seebacher, Frank

2005-10-01

Biological functions are dependent on the temperature of the organism. Animals may respond to fluctuation in the thermal environment by regulating their body temperature and by modifying physiological and biochemical rates. Phenotypic flexibility (reversible phenotypic plasticity, acclimation, or acclimatisation in rate functions occurs in all major taxonomic groups and may be considered as an ancestral condition. Within the Reptilia, representatives from all major groups show phenotypic flexibility in response to long-term or chronic changes in the thermal environment. Acclimation or acclimatisation in reptiles are most commonly assessed by measuring whole animal responses such as oxygen consumption, but whole animal responses are comprised of variation in individual traits such as enzyme activities, hormone expression, and cardiovascular functions. The challenge now lies in connecting the changes in the components to the functioning of the whole animal and its fitness. Experimental designs in research on reptilian thermal physiology should incorporate the capacity for reversible phenotypic plasticity as a null-hypothesis, because the significance of differential body temperature-performance relationships (thermal reaction norms) between individuals, populations, or species cannot be assessed without testing that null-hypothesis.

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

NASA Astrophysics Data System (ADS)

Cleare, Sharlane S.

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

Replacement Behaviors for Identified Functions of Challenging Behaviors

ERIC Educational Resources Information Center

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

2011-01-01

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

The political solidarity model of social change: dynamics of self-categorization in intergroup power relations.

PubMed

Subasic, Emina; Reynolds, Katherine J; Turner, John C

2008-11-01

Social and political change involves a challenge to the status quo in intergroup power relations. Traditionally, the social psychology of social change has focused on disadvantaged minority groups collectively challenging the decisions, actions, and policies of those in positions of established authority. In contrast, this article presents a political solidarity model of social change that explores the process by which members of the majority challenge the authority in solidarity with the minority. It is argued that political solidarity as a social change process involves a contest between the authority and the minority over the meaning of a shared (higher order) identity with the majority. When identity ceases to be shared with the authority and becomes shared with the minority, majority challenge to authority in solidarity with the minority becomes possible. The model's contributions to existing social psychological approaches to social change are also discussed.

Consultancy to dairy farmers relating to animal health and herd health management on small- and medium-sized farms.

PubMed

Pothmann, H; Nechanitzky, K; Sturmlechner, F; Drillich, M

2014-02-01

The objectives of this study were to obtain information about animal health challenges for dairy farmers of small- and medium-sized herds and about the fields in which consultancy services should be improved. The hyperlink to an internet-based survey was sent to 9,021 farmers in Austria. The survey included questions about the participants and their farms, about who is consulting with the farmers with regard to animal health, feeding, sire selection, construction of barns and animal husbandry, about animal health issues farmers find most challenging, and about their demands for improved consultancy services. The questionnaire was completed anonymously. Analyses were stratified by milk yield (categorized) and whether farmers worked full-time or part-time. The overall response rate was 11.3% (n=1,018). The majority of farms kept less than 20 cows (54.0%) or 20 to 50 cows (40.1%). With regard to animal health, the veterinarian was the most important consultant for the majority of farmers (84.6%). On issues related to feeding, sire selection, and stable construction, the veterinarian was seen as a less important consultant than specialists in these fields (20.4, 11.6, and 7.9% suggested the veterinarian as an important consultant in these areas). The survey indicated that reproductive disorders, udder disease, poor conception rate, lameness, and calf diarrhea represent the most important challenges to farmers. Of these, concerns about calf diarrhea were affected by milk yield of the herds and management. More high- than low-yielding farms (11.7 vs. 6.4%) and more full-time than part-time managed herds (9.6 vs.4.3%) regarded calf diarrhea as an important problem. Farmers would welcome improved consultancy with regard to fertility, feeding, and sire selection. The results indicated which animal health issues farmers find particularly challenging and displayed which areas farmers require improved consultancy services. Veterinarians and organizations offering consultancy should take the results into consideration in improving or adapting their advisory services. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Preparing for introduction of a dengue vaccine: recommendations from the 1st Dengue v2V Asia-Pacific Meeting.

PubMed

Lam, Sai Kit; Burke, Donald; Capeding, Maria Rosario; Chong, Chee Keong; Coudeville, Laurent; Farrar, Jeremy; Gubler, Duane; Hadinegoro, Sri Rezeki; Hanna, Jeffrey; Lang, Jean; Lee, Han Lim; Leo, Yee Sin; Luong, Chan Quang; Mahoney, Richard; McBride, John; Mendez-Galvan, Jorge; Ng, Lee Ching; Nimmannitya, Suchitra; Ooi, Eng Eong; Shepard, Donald; Smit, Jaco; Teyssou, Rémy; Thomas, Laurent; Torresi, Joseph; Vasconcelos, Pedro; Wirawan, Dewa Nyoman; Yoksan, Sutee

2011-11-28

Infection with dengue virus is a major public health problem in the Asia-Pacific region and throughout tropical and sub-tropical regions of the world. Vaccination represents a major opportunity to control dengue and several candidate vaccines are in development. Experts in dengue and in vaccine introduction gathered for a two day meeting during which they examined the challenges inherent to the introduction of a dengue vaccine into the national immunisation programmes of countries of the Asia-Pacific. The aim was to develop a series of recommendations to reduce the delay between vaccine licensure and vaccine introduction. Major recommendations arising from the meeting included: ascertaining and publicising the full burden and cost of dengue; changing the perception of dengue in non-endemic countries to help generate global support for dengue vaccination; ensuring high quality active surveillance systems and diagnostics; and identifying sustainable sources of funding, both to support vaccine introduction and to maintain the vaccination programme. The attendees at the meeting were in agreement that with the introduction of an effective vaccine, dengue is a disease that could be controlled, and that in order to ensure a vaccine is introduced as rapidly as possible, there is a need to start preparing now. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of an Extreme Flood on Trace Elements in River Water-From Urban Stream to Major River Basin.

PubMed

Barber, Larry B; Paschke, Suzanne S; Battaglin, William A; Douville, Chris; Fitzgerald, Kevin C; Keefe, Steffanie H; Roth, David A; Vajda, Alan M

2017-09-19

Major floods adversely affect water quality through surface runoff, groundwater discharge, and damage to municipal water infrastructure. Despite their importance, it can be difficult to assess the effects of floods on streamwater chemistry because of challenges collecting samples and the absence of baseline data. This study documents water quality during the September 2013 extreme flood in the South Platte River, Colorado, USA. Weekly time-series water samples were collected from 3 urban source waters (municipal tap water, streamwater, and wastewater treatment facility effluent) under normal-flow and flood conditions. In addition, water samples were collected during the flood at 5 locations along the South Platte River and from 7 tributaries along the Colorado Front Range. Samples were analyzed for 54 major and trace elements. Specific chemical tracers, representing different natural and anthropogenic sources and geochemical behaviors, were used to compare streamwater composition before and during the flood. The results differentiate hydrological processes that affected water quality: (1) in the upper watershed, runoff diluted most dissolved constituents, (2) in the urban corridor and lower watershed, runoff mobilized soluble constituents accumulated on the landscape and contributed to stream loading, and (3) flood-induced groundwater discharge mobilized soluble constituents stored in the vadose zone.

Effects of an extreme flood on trace elements in river water—From urban stream to major river basin

USGS Publications Warehouse

Barber, Larry B.; Paschke, Suzanne; Battaglin, William A.; Douville, Chris; Fitzgerald, Kevin C.; Keefe, Steffanie H.; Roth, David A.; Vajda, Alan M.

2017-01-01

Major floods adversely affect water quality through surface runoff, groundwater discharge, and damage to municipal water infrastructure. Despite their importance, it can be difficult to assess the effects of floods on streamwater chemistry because of challenges collecting samples and the absence of baseline data. This study documents water quality during the September 2013 extreme flood in the South Platte River, Colorado, USA. Weekly time-series water samples were collected from 3 urban source waters (municipal tap water, streamwater, and wastewater treatment facility effluent) under normal-flow and flood conditions. In addition, water samples were collected during the flood at 5 locations along the South Platte River and from 7 tributaries along the Colorado Front Range. Samples were analyzed for 54 major and trace elements. Specific chemical tracers, representing different natural and anthropogenic sources and geochemical behaviors, were used to compare streamwater composition before and during the flood. The results differentiate hydrological processes that affected water quality: (1) in the upper watershed, runoff diluted most dissolved constituents, (2) in the urban corridor and lower watershed, runoff mobilized soluble constituents accumulated on the landscape and contributed to stream loading, and (3) flood-induced groundwater discharge mobilized soluble constituents stored in the vadose zone.

Immunohistochemical study of inducible nitric oxide synthase and tumour necrosis factor alpha response in turbot (Scophthalmus maximus) experimentally infected with Aeromonas salmonicida subsp. salmonicida.

PubMed

Coscelli, Germán; Bermúdez, Roberto; Ronza, Paolo; Losada, Ana Paula; Quiroga, María Isabel

2016-09-01

Aeromonas salmonicida subsp. salmonicida represents one of the major threats in aquaculture, especially in salmonid fish and turbot farming. In order to fight bacterial infections, fish have an immune system composed by innate and specific cellular and humoral elements analogous to those present in mammals. However, innate immunity plays a primordial role against bacterial infections in teleost fish. Among these non-specific mechanisms, the production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) pathway and the tumour necrosis factor-alpha (TNFα) produced by mononuclear phagocytes, are two of the main immune effectors to eliminate bacterial pathogens. In this study, the distribution and kinetic of iNOS and TNFα-producing cells of kidney and spleen of turbot experimentally inoculated with A. salmonicida was assessed by immunohistochemistry. In control and challenged fish, individual iNOS(+) and TNFα(+) cells, showing a similar pattern of distribution, were detected. In challenged fish, the number of immunoreactive cells was significantly increased in the evaluated organs, as well as the melanomacrophage centres showed variable positivity for both antigens. These results indicate that A. salmonicida induced an immune response in challenged turbot, which involved the increase of the activity of iNOS and TNFα in the leukocytic population from kidney and spleen. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Human Microbiota, Infectious Disease, and Global Health: Challenges and Opportunities.

PubMed

Waldman, Abraham J; Balskus, Emily P

2018-01-12

Despite significant advances in treating infectious diseases worldwide, morbidity and mortality associated with pathogen infection remains extraordinarily high and represents a critical scientific and global health challenge. Current strategies to combat these infectious agents include a combination of vaccines, small molecule drugs, increased hygiene standards, and disease-specific interventions. While these approaches have helped to drastically reduce the incidence and number of deaths associated with infection, continued investment in current strategies and the development of novel therapeutic approaches will be required to address these global health threats. Recently, human- and vector-associated microbiotas, the assemblages of microorganisms living on and within their hosts, have emerged as a potentially important factor mediating both infection risk and disease progression. These complex microbial communities are involved in intricate and dynamic interactions with both pathogens as well as the innate and adaptive immune systems of their hosts. Here, we discuss recent findings that have illuminated the importance of resident microbiotas in infectious disease, emphasizing opportunities for novel therapeutic intervention and future challenges for the field. Our discussion will focus on four major global health threats: tuberculosis, malaria, HIV, and enteric/diarrheal diseases. We hope this Perspective will highlight the many opportunities for chemists and chemical biologists in this field as well as inspire efforts to elucidate the mechanisms underlying established disease correlations, identify novel microbiota-based risk factors, and develop new therapeutic interventions.

Insights into mortality patterns and causes of death through a process point of view model.

PubMed

Anderson, James J; Li, Ting; Sharrow, David J

2017-02-01

Process point of view (POV) models of mortality, such as the Strehler-Mildvan and stochastic vitality models, represent death in terms of the loss of survival capacity through challenges and dissipation. Drawing on hallmarks of aging, we link these concepts to candidate biological mechanisms through a framework that defines death as challenges to vitality where distal factors defined the age-evolution of vitality and proximal factors define the probability distribution of challenges. To illustrate the process POV, we hypothesize that the immune system is a mortality nexus, characterized by two vitality streams: increasing vitality representing immune system development and immunosenescence representing vitality dissipation. Proximal challenges define three mortality partitions: juvenile and adult extrinsic mortalities and intrinsic adult mortality. Model parameters, generated from Swedish mortality data (1751-2010), exhibit biologically meaningful correspondences to economic, health and cause-of-death patterns. The model characterizes the twentieth century epidemiological transition mainly as a reduction in extrinsic mortality resulting from a shift from high magnitude disease challenges on individuals at all vitality levels to low magnitude stress challenges on low vitality individuals. Of secondary importance, intrinsic mortality was described by a gradual reduction in the rate of loss of vitality presumably resulting from reduction in the rate of immunosenescence. Extensions and limitations of a distal/proximal framework for characterizing more explicit causes of death, e.g. the young adult mortality hump or cancer in old age are discussed.

Insights into mortality patterns and causes of death through a process point of view model

PubMed Central

Anderson, James J.; Li, Ting; Sharrow, David J.

2016-01-01

Process point of view models of mortality, such as the Strehler-Mildvan and stochastic vitality models, represent death in terms of the loss of survival capacity through challenges and dissipation. Drawing on hallmarks of aging, we link these concepts to candidate biological mechanisms through a framework that defines death as challenges to vitality where distal factors defined the age-evolution of vitality and proximal factors define the probability distribution of challenges. To illustrate the process point of view, we hypothesize that the immune system is a mortality nexus, characterized by two vitality streams: increasing vitality representing immune system development and immunosenescence representing vitality dissipation. Proximal challenges define three mortality partitions: juvenile and adult extrinsic mortalities and intrinsic adult mortality. Model parameters, generated from Swedish mortality data (1751-2010), exhibit biologically meaningful correspondences to economic, health and cause-of-death patterns. The model characterizes the 20th century epidemiological transition mainly as a reduction in extrinsic mortality resulting from a shift from high magnitude disease challenges on individuals at all vitality levels to low magnitude stress challenges on low vitality individuals. Of secondary importance, intrinsic mortality was described by a gradual reduction in the rate of loss of vitality presumably resulting from reduction in the rate of immunosenescence. Extensions and limitations of a distal/proximal framework for characterizing more explicit causes of death, e.g. the young adult mortality hump or cancer in old age are discussed. PMID:27885527

Network for Early Onset Cystic Kidney Diseases—A Comprehensive Multidisciplinary Approach to Hereditary Cystic Kidney Diseases in Childhood

PubMed Central

König, Jens Christian; Titieni, Andrea; Konrad, Martin; Bergmann, C.

2018-01-01

Hereditary cystic kidney diseases comprise a complex group of genetic disorders representing one of the most common causes of end-stage renal failure in childhood. The main representatives are autosomal recessive polycystic kidney disease, nephronophthisis, Bardet–Biedl syndrome, and hepatocyte nuclear factor-1beta nephropathy. Within the last years, genetic efforts have brought tremendous progress for the molecular understanding of hereditary cystic kidney diseases identifying more than 70 genes. Yet, genetic heterogeneity, phenotypic variability, a lack of reliable genotype–phenotype correlations and the absence of disease-specific biomarkers remain major challenges for physicians treating children with cystic kidney diseases. To tackle these challenges comprehensive scientific approaches are urgently needed that match the ongoing “revolution” in genetics and molecular biology with an improved efficacy of clinical data collection. Network for early onset cystic kidney diseases (NEOCYST) is a multidisciplinary, multicenter collaborative combining a detailed collection of clinical data with translational scientific approaches addressing the genetic, molecular, and functional background of hereditary cystic kidney diseases. Consisting of seven work packages, including an international registry as well as a biobank, NEOCYST is not only dedicated to current scientific questions, but also provides a platform for longitudinal clinical surveillance and provides precious sources for high-quality research projects and future clinical trials. Funded by the German Federal Government, the NEOCYST collaborative started in February 2016. Here, we would like to introduce the rationale, design, and objectives of the network followed by a short overview on the current state of progress. PMID:29497606

Identifying Potential Sources of Exposure Along the Child Feces Management Pathway: A Cross-Sectional Study Among Urban Slums in Odisha, India.

PubMed

Majorin, Fiona; Torondel, Belen; Routray, Parimita; Rout, Manaswini; Clasen, Thomas

2017-09-01

Child feces represent a particular health risk to children due to increased prevalence of enteric agents and a higher risk of exposure owing to exploratory behaviors of young children. The safe management of such feces presents a significant challenge, not only for the 2.4 billion who lack access to improved sanitation, but also due to unhygienic feces collection and disposal and poor subsequent handwashing practices. We assessed potential sources of fecal exposure by documenting child feces management practices in a cross-sectional study of 851 children < 5 years of age from 694 households in 42 slums in two cities in Odisha, India. No preambulatory children and only 27.4% of ambulatory children defecated directly in the latrine. Children that did not defecate in a latrine mainly defecated on the ground, whether they were preambulatory or ambulatory. Use of diapers (1.2%) or potties (2.8%) was low. If the feces were removed from the ground, the defecation area was usually cleaned, if at all, only with water. Most children's feces were disposed of in surrounding environment, with only 6.5% deposited into any kind of latrine, including unimproved. Handwashing with soap of the caregiver after child feces disposal and child anal cleaning with soap after defecation was also uncommon. While proper disposal of child feces in an improved latrine still represents a major challenge, control of the risks presented requires attention to the full range of exposures associated to the management of child feces, and not simply the place of disposal.

Identifying Potential Sources of Exposure Along the Child Feces Management Pathway: A Cross-Sectional Study Among Urban Slums in Odisha, India

PubMed Central

Majorin, Fiona; Torondel, Belen; Routray, Parimita; Rout, Manaswini; Clasen, Thomas

2017-01-01

Abstract. Child feces represent a particular health risk to children due to increased prevalence of enteric agents and a higher risk of exposure owing to exploratory behaviors of young children. The safe management of such feces presents a significant challenge, not only for the 2.4 billion who lack access to improved sanitation, but also due to unhygienic feces collection and disposal and poor subsequent handwashing practices. We assessed potential sources of fecal exposure by documenting child feces management practices in a cross-sectional study of 851 children < 5 years of age from 694 households in 42 slums in two cities in Odisha, India. No preambulatory children and only 27.4% of ambulatory children defecated directly in the latrine. Children that did not defecate in a latrine mainly defecated on the ground, whether they were preambulatory or ambulatory. Use of diapers (1.2%) or potties (2.8%) was low. If the feces were removed from the ground, the defecation area was usually cleaned, if at all, only with water. Most children’s feces were disposed of in surrounding environment, with only 6.5% deposited into any kind of latrine, including unimproved. Handwashing with soap of the caregiver after child feces disposal and child anal cleaning with soap after defecation was also uncommon. While proper disposal of child feces in an improved latrine still represents a major challenge, control of the risks presented requires attention to the full range of exposures associated to the management of child feces, and not simply the place of disposal. PMID:28749766

Network for Early Onset Cystic Kidney Diseases-A Comprehensive Multidisciplinary Approach to Hereditary Cystic Kidney Diseases in Childhood.

PubMed

König, Jens Christian; Titieni, Andrea; Konrad, Martin

2018-01-01

Hereditary cystic kidney diseases comprise a complex group of genetic disorders representing one of the most common causes of end-stage renal failure in childhood. The main representatives are autosomal recessive polycystic kidney disease, nephronophthisis, Bardet-Biedl syndrome, and hepatocyte nuclear factor-1beta nephropathy. Within the last years, genetic efforts have brought tremendous progress for the molecular understanding of hereditary cystic kidney diseases identifying more than 70 genes. Yet, genetic heterogeneity, phenotypic variability, a lack of reliable genotype-phenotype correlations and the absence of disease-specific biomarkers remain major challenges for physicians treating children with cystic kidney diseases. To tackle these challenges comprehensive scientific approaches are urgently needed that match the ongoing "revolution" in genetics and molecular biology with an improved efficacy of clinical data collection. Network for early onset cystic kidney diseases (NEOCYST) is a multidisciplinary, multicenter collaborative combining a detailed collection of clinical data with translational scientific approaches addressing the genetic, molecular, and functional background of hereditary cystic kidney diseases. Consisting of seven work packages, including an international registry as well as a biobank, NEOCYST is not only dedicated to current scientific questions, but also provides a platform for longitudinal clinical surveillance and provides precious sources for high-quality research projects and future clinical trials. Funded by the German Federal Government, the NEOCYST collaborative started in February 2016. Here, we would like to introduce the rationale, design, and objectives of the network followed by a short overview on the current state of progress.

Phase Field Model of Hydraulic Fracturing in Poroelastic Media: Fracture Propagation, Arrest, and Branching Under Fluid Injection and Extraction

NASA Astrophysics Data System (ADS)

Santillán, David; Juanes, Ruben; Cueto-Felgueroso, Luis

2018-03-01

The simulation of fluid-driven fracture propagation in a porous medium is a major computational challenge, with applications in geosciences and engineering. The two main families of modeling approaches are those models that represent fractures as explicit discontinuities and solve the moving boundary problem and those that represent fractures as thin damaged zones, solving a continuum problem throughout. The latter family includes the so-called phase field models. Continuum approaches to fracture face validation and verification challenges, in particular grid convergence, well posedness, and physical relevance in practical scenarios. Here we propose a new quasi-static phase field formulation. The approach fully couples fluid flow in the fracture with deformation and flow in the porous medium, discretizes flow in the fracture on a lower-dimension manifold, and employs the fluid flux between the fracture and the porous solid as coupling variable. We present a numerical assessment of the model by studying the propagation of a fracture in the quarter five-spot configuration. We study the interplay between injection flow rate and rock properties and elucidate fracture propagation patterns under the leak-off toughness dominated regime as a function of injection rate, initial fracture length, and poromechanical properties. For the considered injection scenario, we show that the final fracture length depends on the injection rate, and three distinct patterns are observed. We also rationalize the system response using dimensional analysis to collapse the model results. Finally, we propose some simplifications that alleviate the computational cost of the simulations without significant loss of accuracy.

A supramolecular strategy to leverage the liquid-phase exfoliation of graphene in the presence of surfactants: unraveling the role of the length of fatty acids.

PubMed

Haar, Sébastien; Ciesielski, Artur; Clough, Joseph; Yang, Huafeng; Mazzaro, Raffaello; Richard, Fanny; Conti, Simone; Merstorf, Nicolas; Cecchini, Marco; Morandi, Vittorio; Casiraghi, Cinzia; Samorì, Paolo

2015-04-08

Achieving the full control over the production as well as processability of high-quality graphene represents a major challenge with potential interest in the field of fabrication of multifunctional devices. The outstanding effort dedicated to tackle this challenge in the last decade revealed that certain organic molecules are capable of leveraging the exfoliation of graphite with different efficiencies. Here, a fundamental understanding on a straightforward supramolecular approach for producing homogenous dispersions of unfunctionalized and non-oxidized graphene nanosheets in four different solvents is attained, namely N-methyl-2-pyrrolidinone, N,N-dimethylformamide, ortho-dichlorobenzene, and 1,2,4-trichlorobenzene. In particular, a comparative study on the liquid-phase exfoliation of graphene in the presence of linear alkanes of different lengths terminated by a carboxylic-acid head group is performed. These molecules act as graphene dispersion-stabilizing agents during the exfoliation process. The efficiency of the exfoliation in terms of concentration of exfoliated graphene is found to be proportional to the length of the employed fatty acid. Importantly, a high percentage of single-layer graphene flakes is revealed by high-resolution transmission electron microscopy and Raman spectroscopy analyses. A simple yet effective thermodynamic model is developed to interpret the chain-length dependence of the exfoliation yield. This approach relying on the synergistic effect of a ad-hoc solvent and molecules to promote the exfoliation of graphene in liquid media represents a promising and modular strategy towards the rational design of improved dispersion-stabilizing agents. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Confirmation and fine-mapping of a major QTL for resistance to infectious pancreatic necrosis in Atlantic salmon (Salmo salar): population-level associations between markers and trait

PubMed Central

Moen, Thomas; Baranski, Matthew; Sonesson, Anna K; Kjøglum, Sissel

2009-01-01

Background Infectious pancreatic necrosis (IPN) is one of the most prevalent and economically devastating diseases in Atlantic salmon (Salmo salar) farming worldwide. The disease causes large mortalities at both the fry- and post-smolt stages. Family selection for increased IPN resistance is performed through the use of controlled challenge tests, where survival rates of sib-groups are recorded. However, since challenge-tested animals cannot be used as breeding candidates, within-family selection is not performed and only half of the genetic variation for IPN resistance is being exploited. DNA markers linked to quantitative trait loci (QTL) affecting IPN resistance would therefore be a powerful selection tool. The aim of this study was to identify and fine-map QTL for IPN-resistance in Atlantic salmon, for use in marker-assisted selection to increase the rate of genetic improvement for this trait. Results A genome scan was carried out using 10 large full-sib families of challenge-tested Atlantic salmon post-smolts and microsatellite markers distributed across the genome. One major QTL for IPN-resistance was detected, explaining 29% and 83% of the phenotypic and genetic variances, respectively. This QTL mapped to the same location as a QTL recently detected in a Scottish Atlantic salmon population. The QTL was found to be segregating in 10 out of 20 mapping parents, and subsequent fine-mapping with additional markers narrowed the QTL peak to a 4 cM region on linkage group 21. Challenge-tested fry were used to show that the QTL had the same effect on fry as on post-smolt, with the confidence interval for QTL position in fry overlapping the confidence interval found in post-smolts. A total of 178 parents were tested for segregation of the QTL, identifying 72 QTL-heterozygous parents. Genotypes at QTL-heterozygous parents were used to determine linkage phases between alleles at the underlying DNA polymorphism and alleles at single markers or multi-marker haplotypes. One four-marker haplotype was found to be the best predictor of QTL alleles, and was successfully used to deduce genotypes of the underlying polymorphism in 72% of the parents of the next generation within a breeding nucleus. A highly significant population-level correlation was found between deduced alleles at the underlying polymorphism and survival of offspring groups in the fry challenge test, parents with the three deduced genotypes (QQ, Qq, qq) having mean offspring mortality rates of 0.13, 0.32, and 0.49, respectively. The frequency of the high-resistance allele (Q) in the population was estimated to be 0.30. Apart from this major QTL, one other experiment-wise significant QTL for IPN-resistance was detected, located on linkage group 4. Conclusion The QTL confirmed in this study represents a case of a major gene explaining the bulk of genetic variation for a presumed complex trait. QTL genotypes were deduced within most parents of the 2005 generation of a major breeding company, providing a solid framework for linkage-based MAS within the whole population in subsequent generations. Since haplotype-trait associations valid at the population level were found, there is also a potential for MAS based on linkage disequilibrium (LD). However, in order to use MAS across many generations without reassessment of linkage phases between markers and the underlying polymorphism, the QTL needs to be positioned with even greater accuracy. This will require higher marker densities than are currently available. PMID:19664221

Educational Leadership: Key Challenges and Ethical Tensions

ERIC Educational Resources Information Center

Duignan, Patrick

2007-01-01

"Educational Leadership" is a major research book on contemporary leadership challenges for educational leaders. In this groundbreaking new work, educational leaders in schools, including teachers, are provided with ways of analysing and resolving common but complex leadership challenges. Ethical tensions inherent in these challenges are…

Expert Supervisors' Priorities When Working with Easy and Challenging Supervisees

ERIC Educational Resources Information Center

Kemer, Gulsah; Borders, L. DiAnne; Yel, Nedim

2017-01-01

Using Kemer, Borders, and Willse's (2014) concept map as a conceptual model, the authors aimed to understand expert supervisors' priorities with their easy and challenging supervisees. Experts' priorities with easy and challenging supervisees were represented in different parts of the concept map, and they seemed to individualize their work with…

The Australian Computational Earth Systems Simulator

NASA Astrophysics Data System (ADS)

Mora, P.; Muhlhaus, H.; Lister, G.; Dyskin, A.; Place, D.; Appelbe, B.; Nimmervoll, N.; Abramson, D.

2001-12-01

Numerical simulation of the physics and dynamics of the entire earth system offers an outstanding opportunity for advancing earth system science and technology but represents a major challenge due to the range of scales and physical processes involved, as well as the magnitude of the software engineering effort required. However, new simulation and computer technologies are bringing this objective within reach. Under a special competitive national funding scheme to establish new Major National Research Facilities (MNRF), the Australian government together with a consortium of Universities and research institutions have funded construction of the Australian Computational Earth Systems Simulator (ACcESS). The Simulator or computational virtual earth will provide the research infrastructure to the Australian earth systems science community required for simulations of dynamical earth processes at scales ranging from microscopic to global. It will consist of thematic supercomputer infrastructure and an earth systems simulation software system. The Simulator models and software will be constructed over a five year period by a multi-disciplinary team of computational scientists, mathematicians, earth scientists, civil engineers and software engineers. The construction team will integrate numerical simulation models (3D discrete elements/lattice solid model, particle-in-cell large deformation finite-element method, stress reconstruction models, multi-scale continuum models etc) with geophysical, geological and tectonic models, through advanced software engineering and visualization technologies. When fully constructed, the Simulator aims to provide the software and hardware infrastructure needed to model solid earth phenomena including global scale dynamics and mineralisation processes, crustal scale processes including plate tectonics, mountain building, interacting fault system dynamics, and micro-scale processes that control the geological, physical and dynamic behaviour of earth systems. ACcESS represents a part of Australia's contribution to the APEC Cooperation for Earthquake Simulation (ACES) international initiative. Together with other national earth systems science initiatives including the Japanese Earth Simulator and US General Earthquake Model projects, ACcESS aims to provide a driver for scientific advancement and technological breakthroughs including: quantum leaps in understanding of earth evolution at global, crustal, regional and microscopic scales; new knowledge of the physics of crustal fault systems required to underpin the grand challenge of earthquake prediction; new understanding and predictive capabilities of geological processes such as tectonics and mineralisation.

How effective are traditional methods of compositional analysis in providing an accurate material balance for a range of softwood derived residues?

PubMed Central

2013-01-01

Background Forest residues represent an abundant and sustainable source of biomass which could be used as a biorefinery feedstock. Due to the heterogeneity of forest residues, such as hog fuel and bark, one of the expected challenges is to obtain an accurate material balance of these feedstocks. Current compositional analytical methods have been standardised for more homogenous feedstocks such as white wood and agricultural residues. The described work assessed the accuracy of existing and modified methods on a variety of forest residues both before and after a typical pretreatment process. Results When “traditional” pulp and paper methods were used, the total amount of material that could be quantified in each of the six softwood-derived residues ranged from 88% to 96%. It was apparent that the extractives present in the substrate were most influential in limiting the accuracy of a more representative material balance. This was particularly evident when trying to determine the lignin content, due to the incomplete removal of the extractives, even after a two stage water-ethanol extraction. Residual extractives likely precipitated with the acid insoluble lignin during analysis, contributing to an overestimation of the lignin content. Despite the minor dissolution of hemicellulosic sugars, extraction with mild alkali removed most of the extractives from the bark and improved the raw material mass closure to 95% in comparison to the 88% value obtained after water-ethanol extraction. After pretreatment, the extent of extractive removal and their reaction/precipitation with lignin was heavily dependent on the pretreatment conditions used. The selective removal of extractives and their quantification after a pretreatment proved to be even more challenging. Regardless of the amount of extractives that were originally present, the analytical methods could be refined to provide reproducible quantification of the carbohydrates present in both the starting material and after pretreatment. Conclusion Despite the challenges resulting from the heterogeneity of the initial biomass substrates a reasonable summative mass closure could be obtained before and after steam pretreatment. However, method revision and optimisation was required, particularly the effective removal of extractives, to ensure that representative and reproducible values for the major lignin and carbohydrate components. PMID:23800175

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

PubMed

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

2015-03-01

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

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

PubMed Central

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

2015-01-01

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

Female specialists in intensive care medicine: job satisfaction, challenges and work-life balance.

PubMed

Hawker, Felicity H

2016-06-01

Women are under-represented in the intensive care medicine (ICM) specialist workforce. I aimed to better understand the challenges these women face so they can be considered in the training and support of ICM specialists. All female Fellows of the College of Intensive Care Medicine (CICM) of Australia and New Zealand were surveyed using an online questionnaire. The study was approved by the Cabrini Human Research Ethics Committee. Thirty respondents with children volunteered to complete a second questionnaire. I surveyed demographic and workforce data and women's experiences in the ICM specialist workforce in the first survey, and experiences with child-rearing in the second survey. The response rate was 80.3% (127/158). The median age bracket was 40-45 years, and 118 respondents were practising ICM, 85 full-time in a tertiary intensive care unit. Eighteen were ICU directors and 23 were CICM-appointed supervisors of training. Sixty-five women were mothers, and 70% returned to full-time work after their maternity leave. Child care was most commonly undertaken by family members or a nanny. Overall, 81% were satisfied with their experiences, but 37% felt they had been disadvantaged because of their sex. Fewer women with leadership roles felt disadvantaged. Their major challenges included the on-call work affecting child-rearing and family life, sexism in the workplace and difficulties with academic advancement. The participation and satisfaction rates of women working in the ICM specialist workforce are encouraging. Although challenges exist, women contemplating a career in ICM should see it as achievable and rewarding.

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

PubMed Central

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

2013-01-01

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

Learning for Vocation Apprentice Participation in Work Practice

ERIC Educational Resources Information Center

Lyngsnes, Kitt; Rismark, Marit

2011-01-01

The high drop-out rate in upper secondary education is a major challenge to European and US educational programmes. Upper secondary education in Norway faces a similar challenge, because in recent decades, around one-third of the students drop out of the educational programmes. The majority of the drop-outs are students in vocational programmes,…

Families, Schools, and Major Demographic Trends in the United States

ERIC Educational Resources Information Center

Crosnoe, Robert; Benner, Aprile D.

2012-01-01

Although long-term social change is challenging to study, it is theoretically important because its effects are not immediate and it is not usually powered by major social institutions. Another challenge is that individuals are often only vaguely aware of long-term social changes and do not fully consider how they might be affected personally. As…

Student Attraction, Persistence and Retention in STEM Programs: Successes and Continuing Challenges

ERIC Educational Resources Information Center

Sithole, Alec; Chiyaka, Edward T.; McCarthy, Peter; Mupinga, Davison M.; Bucklein, Brian K.; Kibirige, Joachim

2017-01-01

Low student enrollment and high attrition rates in Science, Technology, Engineering, and Mathematics (STEM) education are major challenges in higher education. Many STEM entrants end-up switching their majors to non-STEM fields, perform poorly relative to their peers in other programs, and/or drop out of college without earning any academic…

Internationally educated nurses' reflections on nursing communication in Canada.

PubMed

Lum, L; Dowedoff, P; Englander, K

2016-09-01

The overall goal of this study was to explore internationally educated nurses' perceptions of the English language and nursing communication skill requirements in a Canadian bridging education program. The increased global mobility of nurses creates a need to address the educational needs of migrating nurses. A large percentage of these nurses require additional language and professional education. New research is needed that would represent an in-depth analysis of their educational experiences associated with learning academic English and Canadian nursing communication. Developing proficiency with a new language has been documented as posing challenges for new immigrants. Since language proficiency is a key requirement of Canadian nursing regulatory bodies, previously unrecognized barriers such as attitudes and beliefs about required English language and nursing communication competency which may hinder their ability to meet local practice standards need to be explored. Using a grounded theory study design, narratives from 22 participants from the Philippines, Nigeria and Europe enrolled in bridging education were collected and analysed. The participants identified the incongruence in professional norms between Canada and their home country as a major challenge. The major themes identified included cultural dissonance, academic literacy challenges and skepticism regarding unexpected communication competency requirements. The participants possessed varying degrees of comprehension and acceptance of new educational and professional regulatory requirements. A certain degree of culture shock, which may be associated with frustration and disillusionment, is a typical and anticipated aspect of the immigration process. Their perceptions need to be recognized and accommodated when assisting internationally educated nurses to integrate into the Canadian practice culture. Any generalizations to other host countries need to be made cautiously. Clear communication from regulators about English language and nursing communication requirements during the pre-arrival period is recommended. If bridging education is required, these programs need to be designed to address English language competency and nursing communication skills of non-native English speakers. © 2016 International Council of Nurses.

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

NASA Astrophysics Data System (ADS)

Mateo-Marti, Eva

2014-08-01

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

Physically based model for extracting dual permeability parameters using non-Newtonian fluids

NASA Astrophysics Data System (ADS)

Abou Najm, M. R.; Basset, C.; Stewart, R. D.; Hauswirth, S.

2017-12-01

Dual permeability models are effective for the assessment of flow and transport in structured soils with two dominant structures. The major challenge to those models remains in the ability to determine appropriate and unique parameters through affordable, simple, and non-destructive methods. This study investigates the use of water and a non-Newtonian fluid in saturated flow experiments to derive physically-based parameters required for improved flow predictions using dual permeability models. We assess the ability of these two fluids to accurately estimate the representative pore sizes in dual-domain soils, by determining the effective pore sizes of macropores and micropores. We developed two sub-models that solve for the effective macropore size assuming either cylindrical (e.g., biological pores) or planar (e.g., shrinkage cracks and fissures) pore geometries, with the micropores assumed to be represented by a single effective radius. Furthermore, the model solves for the percent contribution to flow (wi) corresponding to the representative macro and micro pores. A user-friendly solver was developed to numerically solve the system of equations, given that relevant non-Newtonian viscosity models lack forms conducive to analytical integration. The proposed dual-permeability model is a unique attempt to derive physically based parameters capable of measuring dual hydraulic conductivities, and therefore may be useful in reducing parameter uncertainty and improving hydrologic model predictions.

Fungi in the cystic fibrosis lung: bystanders or pathogens?

PubMed

Chotirmall, Sanjay H; McElvaney, Noel G

2014-07-01

Improvement to the life expectancy of people with cystic fibrosis (PWCF) brings about novel challenges including the need for evaluation of the role of fungi in the cystic fibrosis (CF) lung. To determine if such organisms represent bystanders or pathogens affecting clinical outcomes we review the existing knowledge from a clinical, biochemical, inflammatory and immunological perspective. The prevalence and importance of fungi in the CF airway has likely been underestimated with the most frequently isolated filamentous fungi being Aspergillus fumigatus and Scedosporium apiospermum and the major yeast Candida albicans. Developing non-culture based microbiological methods for fungal detection has improved both our classification and understanding of their clinical consequences including localized, allergic and systemic infections. Cross-kingdom interaction between bacteria and fungi are discussed as is the role of biofilms further affecting clinical outcome. A combination of host and pathogen-derived factors determines if a particular fungus represents a commensal, colonizer or pathogen in the setting of CF. The underlying immune state, disease severity and treatment burden represent key host variables whilst fungal type, form, chronicity and virulence including the ability to evade immune recognition determines the pathogenic potential of a specific fungus at a particular point in time. Further research in this emerging field is warranted to fully elucidate the spectrum of disease conferred by the presence of fungi in the CF airway and the indications for therapeutic interventions. Copyright © 2014. Published by Elsevier Ltd.

Transitions to Care in the Community for Prison Releasees with HIV: a Qualitative Study of Facilitators and Challenges in Two States.

PubMed

Hammett, Theodore M; Donahue, Sara; LeRoy, Lisa; Montague, Brian T; Rosen, David L; Solomon, Liza; Costa, Michael; Wohl, David; Rich, Josiah D

2015-08-01

One in seven people living with HIV in the USA passes through a prison or jail each year, and almost all will return to the community. Discharge planning and transitional programs are critical but challenging elements in ensuring continuity of care, maintaining treatment outcomes achieved in prison, and preventing further viral transmission. This paper describes facilitators and challenges of in-prison care, transitional interventions, and access to and continuity of care in the community in Rhode Island and North Carolina based on qualitative data gathered as part of the mixed-methods Link Into Care Study of prisoners and releasees with HIV. We conducted 65 interviews with correctional and community-based providers and administrators and analyzed the transcripts using NVivo 10 to identify major themes. Facilitators of effective transitional systems in both states included the following: health providers affiliated with academic institutions or other entities independent of the corrections department; organizational philosophy emphasizing a patient-centered, personal, and holistic approach; strong leadership with effective "champions"; a team approach with coordination, collaboration and integration throughout the system, mutual respect and learning between corrections and health providers, staff dedicated to transitional services, and effective communication and information sharing among providers; comprehensive transitional activities and services including HIV, mental health and substance use services in prisons, timely and comprehensive discharge planning with specific linkages/appointments, supplies of medications on release, access to benefits and entitlements, case management and proactive follow-up on missed appointments; and releasees' commitment to transitional plans. These elements were generally present in both study states but their absence, which also sometimes occurred, represent ongoing challenges to success. The qualitative findings on the facilitators and challenges of the transitional systems were similar in the two states despite differences in context, demographics of target population, and system organization. Recommendations for improved transitional systems follow from the analysis of the facilitators and challenges.

Respiratory medicine in China: progress, challenges, and opportunities.

PubMed

Wang, Chen; Xiao, Fei; Qiao, Renli; Shen, Ying H

2013-06-01

The past century witnessed a rapid development of respiratory medicine in China. The major burden of respiratory disease has shifted from infectious diseases to chronic noninfectious diseases. Great achievements have been made in improving the national standard of clinical management of various respiratory diseases and in smoking control. The specialty of respiratory medicine is expanding into pulmonary and critical care medicine. Nevertheless, respiratory diseases remain a major public health problem, with new challenges such as air pollution and nosocomial infections. This review describes the history, accomplishments, new challenges, and opportunities in respiratory medicine in China.

Challenges for modeling global gene regulatory networks during development: insights from Drosophila.

PubMed

Wilczynski, Bartek; Furlong, Eileen E M

2010-04-15

Development is regulated by dynamic patterns of gene expression, which are orchestrated through the action of complex gene regulatory networks (GRNs). Substantial progress has been made in modeling transcriptional regulation in recent years, including qualitative "coarse-grain" models operating at the gene level to very "fine-grain" quantitative models operating at the biophysical "transcription factor-DNA level". Recent advances in genome-wide studies have revealed an enormous increase in the size and complexity or GRNs. Even relatively simple developmental processes can involve hundreds of regulatory molecules, with extensive interconnectivity and cooperative regulation. This leads to an explosion in the number of regulatory functions, effectively impeding Boolean-based qualitative modeling approaches. At the same time, the lack of information on the biophysical properties for the majority of transcription factors within a global network restricts quantitative approaches. In this review, we explore the current challenges in moving from modeling medium scale well-characterized networks to more poorly characterized global networks. We suggest to integrate coarse- and find-grain approaches to model gene regulatory networks in cis. We focus on two very well-studied examples from Drosophila, which likely represent typical developmental regulatory modules across metazoans. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Acceptable bit-rates for human face identification from CCTV imagery

NASA Astrophysics Data System (ADS)

Tsifouti, Anastasia; Triantaphillidou, Sophie; Bilissi, Efthimia; Larabi, Mohamed-Chaker

2013-01-01

The objective of this investigation is to produce recommendations for acceptable bit-rates of CCTV footage of people onboard London buses. The majority of CCTV recorders on buses use a proprietary format based on the H.264/AVC video coding standard, exploiting both spatial and temporal redundancy. Low bit-rates are favored in the CCTV industry but they compromise the image usefulness of the recorded imagery. In this context usefulness is defined by the presence of enough facial information remaining in the compressed image to allow a specialist to identify a person. The investigation includes four steps: 1) Collection of representative video footage. 2) The grouping of video scenes based on content attributes. 3) Psychophysical investigations to identify key scenes, which are most affected by compression. 4) Testing of recording systems using the key scenes and further psychophysical investigations. The results are highly dependent upon scene content. For example, very dark and very bright scenes were the most challenging to compress, requiring higher bit-rates to maintain useful information. The acceptable bit-rates are also found to be dependent upon the specific CCTV system used to compress the footage, presenting challenges in drawing conclusions about universal `average' bit-rates.

Parameters of the Endocannabinoid System as Novel Biomarkers in Sepsis and Septic Shock.

PubMed

Lafreniere, J Daniel; Lehmann, Christian

2017-11-01

Sepsis represents a dysregulated immune response to infection, with a continuum of severity progressing to septic shock. This dysregulated response generally follows a pattern by which an initial hyperinflammatory phase is followed by a state of sepsis-associated immunosuppression. Major challenges in improving sepsis care include developing strategies to ensure early and accurate identification and diagnosis of the disease process, improving our ability to predict outcomes and stratify patients, and the need for novel sepsis-specific treatments such as immunomodulation. Biomarkers offer promise with all three of these challenges and are likely also to be the solution to determining a patient's immune status; something that is critical in guiding effective and safe immunomodulatory therapy. Currently available biomarkers used in sepsis lack sensitivity and specificity, among other significant shortcomings. The endocannabinoid system (ECS) is an emerging topic of research with evidence suggesting a ubiquitous presence on both central and peripheral tissues, including an intrinsic link with immune function. This review will first discuss the state of sepsis biomarkers and lack of available treatments, followed by an introduction to the ECS and a discussion of its potential to provide novel biomarkers and treatments.

Satellite Tracking of Manta Rays Highlights Challenges to Their Conservation

PubMed Central

Graham, Rachel T.; Witt, Matthew J.; Castellanos, Dan W.; Remolina, Francisco; Maxwell, Sara; Godley, Brendan J.; Hawkes, Lucy A.

2012-01-01

We describe the real-time movements of the last of the marine mega-vertebrate taxa to be satellite tracked – the giant manta ray (or devil fish, Manta birostris), the world's largest ray at over 6 m disc width. Almost nothing is known about manta ray movements and their environmental preferences, making them one of the least understood of the marine mega-vertebrates. Red listed by the International Union for the Conservation of Nature as ‘Vulnerable’ to extinction, manta rays are known to be subject to direct and incidental capture and some populations are declining. Satellite-tracked manta rays associated with seasonal upwelling events and thermal fronts off the Yucatan peninsula, Mexico, and made short-range shuttling movements, foraging along and between them. The majority of locations were received from waters shallower than 50 m deep, representing thermally dynamic and productive waters. Manta rays remained in the Mexican Exclusive Economic Zone for the duration of tracking but only 12% of tracking locations were received from within Marine Protected Areas (MPAs). Our results on the spatio-temporal distribution of these enigmatic rays highlight opportunities and challenges to management efforts. PMID:22590622

Recent Advances in Exosomal Protein Detection Via Liquid Biopsy Biosensors for Cancer Screening, Diagnosis, and Prognosis.

PubMed

Liu, Chang; Yang, Yunchen; Wu, Yun

2018-03-08

Current cancer diagnostic methods are challenged by low sensitivity, high false positive rate, limited tumor information, uncomfortable or invasive procedures, and high cost. Liquid biopsy that analyzes circulating biomarkers in body fluids represents a promising solution to these challenges. Exosomes are one of the promising cancer biomarkers for liquid biopsy because they are cell-secreted, nano-sized, extracellular vesicles that stably exist in all types of body fluids. Exosomes transfer DNAs, RNAs, proteins, and lipids from parent cells to recipient cells for intercellular communication and play important roles in cancer initiation, progression, and metastasis. Many liquid biopsy biosensors have been developed to offer non- or minimally-invasive, highly sensitive, simple, rapid, and cost-effective cancer diagnostics. This review summarized recent advances of liquid biopsy biosensors with a focus on the detection of exosomal proteins as biomarkers for cancer screening, diagnosis, and prognosis. We reviewed six major types of liquid biopsy biosensors including immunofluorescence biosensor, colorimetric biosensor, surface plasmon resonance (SPR) biosensor, surface-enhanced Raman scattering (SERS) biosensor, electrochemical biosensor, and nuclear magnetic resonance (NMR) biosensor. We shared our perspectives on future improvement of exosome-based liquid biopsy biosensors to accelerate their clinical translation.

Nanoinformatics knowledge infrastructures: bringing efficient information management to nanomedical research.

PubMed

de la Iglesia, D; Cachau, R E; García-Remesal, M; Maojo, V

2013-11-27

Nanotechnology represents an area of particular promise and significant opportunity across multiple scientific disciplines. Ongoing nanotechnology research ranges from the characterization of nanoparticles and nanomaterials to the analysis and processing of experimental data seeking correlations between nanoparticles and their functionalities and side effects. Due to their special properties, nanoparticles are suitable for cellular-level diagnostics and therapy, offering numerous applications in medicine, e.g. development of biomedical devices, tissue repair, drug delivery systems and biosensors. In nanomedicine, recent studies are producing large amounts of structural and property data, highlighting the role for computational approaches in information management. While in vitro and in vivo assays are expensive, the cost of computing is falling. Furthermore, improvements in the accuracy of computational methods (e.g. data mining, knowledge discovery, modeling and simulation) have enabled effective tools to automate the extraction, management and storage of these vast data volumes. Since this information is widely distributed, one major issue is how to locate and access data where it resides (which also poses data-sharing limitations). The novel discipline of nanoinformatics addresses the information challenges related to nanotechnology research. In this paper, we summarize the needs and challenges in the field and present an overview of extant initiatives and efforts.

Complementary MS Methods Assist Conformational Characterization of Antibodies with Altered S-S Bonding Networks

NASA Astrophysics Data System (ADS)

Jones, Lisa M.; Zhang, Hao; Cui, Weidong; Kumar, Sandeep; Sperry, Justin B.; Carroll, James A.; Gross, Michael L.

2013-06-01

As therapeutic monoclonal antibodies (mAbs) become a major focus in biotechnology and a source of the next-generation drugs, new analytical methods or combination methods are needed for monitoring changes in higher order structure and effects of post-translational modifications. The complexity of these molecules and their vulnerability to structural change provide a serious challenge. We describe here the use of complementary mass spectrometry methods that not only characterize mutant mAbs but also may provide a general framework for characterizing higher order structure of other protein therapeutics and biosimilars. To frame the challenge, we selected members of the IgG2 subclass that have distinct disulfide isomeric structures as a model to evaluate an overall approach that uses ion mobility, top-down MS sequencing, and protein footprinting in the form of fast photochemical oxidation of proteins (FPOP). These three methods are rapid, sensitive, respond to subtle changes in conformation of Cys → Ser mutants of an IgG2, each representing a single disulfide isoform, and may be used in series to probe higher order structure. The outcome suggests that this approach of using various methods in combination can assist the development and quality control of protein therapeutics.

Deletion of ssnA Attenuates the Pathogenicity of Streptococcus suis and Confers Protection against Serovar 2 Strain Challenge.

PubMed

Li, Miao; Cai, Ru-Jian; Li, Chun-Ling; Song, Shuai; Li, Yan; Jiang, Zhi-Yong; Yang, Dong-Xia

2017-01-01

Streptococcus suis serotype 2 (SS2) is a major porcine and human pathogen which causes arthritis, meningitis, and septicemia. Streptococcus suis nuclease A (SsnA) is a recently discovered deoxyribonuclease (DNase), which has been demonstrated to contribute to escape killing in neutrophil extracellular traps (NETs). To further determine the effects of ssnA on virulence, the ssnA deletion mutant (ΔssnA) and its complemented strain (C-ΔssnA) were constructed. The ability of ΔssnA mutant to interact with human laryngeal epithelial cell (Hep-2) was evaluated and it exhibited dramatically decreased ability to adhere to and invade Hep-2 cells. This mutation was found to exhibit significant attenuation of virulence when evaluated in CD1 mice, suggesting ssnA plays a critical role in the pathogenesis of SS2. Finally, we found that immunization with the ΔssnA mutant triggered both antibody responses and cell-mediated immunity, and conferred 80% protection against virulent SS2 challenge in mice. Taken together, our results suggest that ΔssnA represents an attractive candidate for designing an attenuated live vaccine against SS2.

Efforts at Broadening Participation in the Sciences: An Examination of the Mentoring Experiences of Students from Underrepresented Groups

PubMed Central

Prunuske, Amy; Wilson, Janelle; Walls, Melissa; Marrin, Hannah; Clarke, Benjamin

2016-01-01

With the primary objective of attracting and retaining students from underrepresented backgrounds in the sciences, evaluation of one institution’s program has been ongoing over the past three years. Interviews with mentors in the program followed by focus groups conducted with mentees reveal key factors that shape undergraduate students’ research experiences. In the present study, attention is given to data gathered from 15 mentees in the program, the majority of whom have enrolled in community colleges, represent low socioeconomic backgrounds, and are nontraditional students. The results from focus groups with the mentees provide information on the benefits of participating in the program, characteristics of good mentors, challenges to the mentoring relationship, and the effects of underrepresented status on pursuit of advanced degrees. Comparisons of mentees’ comments about the mentoring relationship with mentors’ comments reveal similar themes and patterns while also demonstrating interesting differences. The qualitative findings are also juxtaposed with participants’ responses on the Survey of Undergraduate Research Experiences. Taken together, the data enhance our understanding of the experiences of underrepresented students in faculty-mentored research programs and highlight challenges and perspectives of students who are transferring to the university from a community college. PMID:27521233

Lightweight Provenance Service for High-Performance Computing

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

Dai, Dong; Chen, Yong; Carns, Philip

Provenance describes detailed information about the history of a piece of data, containing the relationships among elements such as users, processes, jobs, and workflows that contribute to the existence of data. Provenance is key to supporting many data management functionalities that are increasingly important in operations such as identifying data sources, parameters, or assumptions behind a given result; auditing data usage; or understanding details about how inputs are transformed into outputs. Despite its importance, however, provenance support is largely underdeveloped in highly parallel architectures and systems. One major challenge is the demanding requirements of providing provenance service in situ. Themore » need to remain lightweight and to be always on often conflicts with the need to be transparent and offer an accurate catalog of details regarding the applications and systems. To tackle this challenge, we introduce a lightweight provenance service, called LPS, for high-performance computing (HPC) systems. LPS leverages a kernel instrument mechanism to achieve transparency and introduces representative execution and flexible granularity to capture comprehensive provenance with controllable overhead. Extensive evaluations and use cases have confirmed its efficiency and usability. We believe that LPS can be integrated into current and future HPC systems to support a variety of data management needs.« less

Advancing the field of 3D biomaterial printing.

PubMed

Jakus, Adam E; Rutz, Alexandra L; Shah, Ramille N

2016-01-11

3D biomaterial printing has emerged as a potentially revolutionary technology, promising to transform both research and medical therapeutics. Although there has been recent progress in the field, on-demand fabrication of functional and transplantable tissues and organs is still a distant reality. To advance to this point, there are two major technical challenges that must be overcome. The first is expanding upon the limited variety of available 3D printable biomaterials (biomaterial inks), which currently do not adequately represent the physical, chemical, and biological complexity and diversity of tissues and organs within the human body. Newly developed biomaterial inks and the resulting 3D printed constructs must meet numerous interdependent requirements, including those that lead to optimal printing, structural, and biological outcomes. The second challenge is developing and implementing comprehensive biomaterial ink and printed structure characterization combined with in vitro and in vivo tissue- and organ-specific evaluation. This perspective outlines considerations for addressing these technical hurdles that, once overcome, will facilitate rapid advancement of 3D biomaterial printing as an indispensable tool for both investigating complex tissue and organ morphogenesis and for developing functional devices for a variety of diagnostic and regenerative medicine applications.

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.

Multiscale Porosity and Mechanical Properties of Mancos Shale: Evaluation of REV and Scale Separation

NASA Astrophysics Data System (ADS)

Heath, J. E.; Dewers, T. A.; Yoon, H.; Mozley, P.

2016-12-01

Heterogeneity from the nanometer to core and larger length scales is a major challenge to understanding coupled processes in shale. To develop methods to address this challenge, we present application of high throughput multi-beam scanning electron microscopy (mSEM) and nano-to-micro-scale mechanics to the Mancos Shale. We use a 61-beam mSEM to collect 6 nm resolution SEM images at the scale of several square millimeters. These images are analyzed for pore size and shape characteristics including spatial correlation and structure. Nano-indentation, micropillar compression, and axisymmetric testing at multiple length scales allows for examining the influence of sampling size on mechanical response. The combined data set is used to: investigate representative elementary volumes (and areas for the 2D images) for the Mancos Shale; determine if scale separation occurs; and determine if transport and mechanical properties at a given length scale can be statistically defined. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Nanoinformatics knowledge infrastructures: bringing efficient information management to nanomedical research

NASA Astrophysics Data System (ADS)

de la Iglesia, D.; Cachau, R. E.; García-Remesal, M.; Maojo, V.

2013-01-01

Nanotechnology represents an area of particular promise and significant opportunity across multiple scientific disciplines. Ongoing nanotechnology research ranges from the characterization of nanoparticles and nanomaterials to the analysis and processing of experimental data seeking correlations between nanoparticles and their functionalities and side effects. Due to their special properties, nanoparticles are suitable for cellular-level diagnostics and therapy, offering numerous applications in medicine, e.g. development of biomedical devices, tissue repair, drug delivery systems and biosensors. In nanomedicine, recent studies are producing large amounts of structural and property data, highlighting the role for computational approaches in information management. While in vitro and in vivo assays are expensive, the cost of computing is falling. Furthermore, improvements in the accuracy of computational methods (e.g. data mining, knowledge discovery, modeling and simulation) have enabled effective tools to automate the extraction, management and storage of these vast data volumes. Since this information is widely distributed, one major issue is how to locate and access data where it resides (which also poses data-sharing limitations). The novel discipline of nanoinformatics addresses the information challenges related to nanotechnology research. In this paper, we summarize the needs and challenges in the field and present an overview of extant initiatives and efforts.

The development of a national HIV Plan in Belgium: Achieving consensus despite institutional complexity.

PubMed

Schweikardt, Christoph; Coppieters, Yves

2015-10-01

The development of a national HIV Plan poses serious challenges to countries with a complex distribution of legal powers such as Belgium. This article explores how the Belgian national HIV Plan 2014-2019 was developed. Applying the policy streams model of John Kingdon, the analysis of the HIV Plan development process was based on published government statements, parliamentary documents, and websites of stakeholders. The Federal Ministry of Health initiative to achieve the HIV Plan was characterized by a coordinating role with a participatory approach towards the other Belgian governments and stakeholders. The 2013 protocol agreement of the Belgian governments committed them to principles, actions, and cooperation, but not to budgets, priorities, or target figures. The Federal government followed a successful strategy to create momentum and commitment to a common national vision on HIV/AIDS. The window of opportunity was not sufficient to create an implementation plan prior to the 2014 elections, and major challenges were left to the subsequent governments, including financing. The country of Belgium represents an example of a consensus strategy to achieve a national HIV Plan with its achievements and limits within institutional complexity and limited Federal legal powers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The changing face of hemostasis testing in modern laboratories: consolidation, automation, and beyond.

PubMed

Lippi, Giuseppe; Plebani, Mario; Favaloro, Emmanuel J

2015-04-01

The reality of laboratory diagnostics as a whole, and hemostasis testing in particular, is evolving under new paradigms of efficiency. The driving forces of health care and laboratory diagnostics in the third millennium are mainly represented by macro- and microeconomics. In a world with limited resources, shattered by an unprecedented economic crisis, laboratory diagnostics is undergoing a substantial reorganization, with emergence of new models under the imperative of terms, such as bedside testing, consolidation, and networking. The paradigms under which these changes are being developed include a variety of environment, preanalytical, technological, professional, and health-care aspects. The maintenance of continued quality is indeed the major challenge to be faced in the foreseeable future. In fact, some challenges prepotently emerge during a consolidation process, which basically involve delayed testing, centrifugation, transportation, and stability of the specimens, as well as the potential mismatch of sample matrix. This article is aimed to provide an overview of the current economic scenario of laboratory diagnostics and discuss the changing face of hemostasis testing in modern laboratories, providing a synthetic overview about potential drawbacks of actualized solutions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Vaccination with Eimeria tenella elongation factor-1α recombinant protein induces protective immunity against E. tenella and E. maxima infections.

PubMed

Lin, Rui-Qing; Lillehoj, Hyun S; Lee, Seung Kyoo; Oh, Sungtaek; Panebra, Alfredo; Lillehoj, Erik P

2017-08-30

Avian coccidiosis is caused by multiple species of the apicomplexan protozoan, Eimeria, and is one of the most economically devastating enteric diseases for the poultry industry worldwide. Host immunity to Eimeria infection, however, is relatively species-specific. The ability to immunize chickens against different species of Eimeria using a single vaccine will have a major beneficial impact on commercial poultry production. In this paper, we describe the molecular cloning, purification, and vaccination efficacy of a novel Eimeria vaccine candidate, elongation factor-1α (EF-1α). One day-old broiler chickens were given two subcutaneous immunizations one week apart with E. coli-expressed E. tenella recombinant (r)EF-1α protein and evaluated for protection against challenge infection with E. tenella or E. maxima. rEF-1α-vaccinated chickens exhibited increased body weight gains, decreased fecal oocyst output, and greater serum anti-EF-1α antibody levels following challenge infection with either E. tenella or E. maxima compared with unimmunized controls. Vaccination with EF-1α may represent a new approach to inducing cross-protective immunity against avian coccidiosis in the field. Published by Elsevier B.V.

DANoC: An Efficient Algorithm and Hardware Codesign of Deep Neural Networks on Chip.

PubMed

Zhou, Xichuan; Li, Shengli; Tang, Fang; Hu, Shengdong; Lin, Zhi; Zhang, Lei

2017-07-18

Deep neural networks (NNs) are the state-of-the-art models for understanding the content of images and videos. However, implementing deep NNs in embedded systems is a challenging task, e.g., a typical deep belief network could exhaust gigabytes of memory and result in bandwidth and computational bottlenecks. To address this challenge, this paper presents an algorithm and hardware codesign for efficient deep neural computation. A hardware-oriented deep learning algorithm, named the deep adaptive network, is proposed to explore the sparsity of neural connections. By adaptively removing the majority of neural connections and robustly representing the reserved connections using binary integers, the proposed algorithm could save up to 99.9% memory utility and computational resources without undermining classification accuracy. An efficient sparse-mapping-memory-based hardware architecture is proposed to fully take advantage of the algorithmic optimization. Different from traditional Von Neumann architecture, the deep-adaptive network on chip (DANoC) brings communication and computation in close proximity to avoid power-hungry parameter transfers between on-board memory and on-chip computational units. Experiments over different image classification benchmarks show that the DANoC system achieves competitively high accuracy and efficiency comparing with the state-of-the-art approaches.

Chess Revision: Acquiring the Rules of Chess Variants through FOL Theory Revision from Examples

NASA Astrophysics Data System (ADS)

Muggleton, Stephen; Paes, Aline; Santos Costa, Vítor; Zaverucha, Gerson

The game of chess has been a major testbed for research in artificial intelligence, since it requires focus on intelligent reasoning. Particularly, several challenges arise to machine learning systems when inducing a model describing legal moves of the chess, including the collection of the examples, the learning of a model correctly representing the official rules of the game, covering all the branches and restrictions of the correct moves, and the comprehensibility of such a model. Besides, the game of chess has inspired the creation of numerous variants, ranging from faster to more challenging or to regional versions of the game. The question arises if it is possible to take advantage of an initial classifier of chess as a starting point to obtain classifiers for the different variants. We approach this problem as an instance of theory revision from examples. The initial classifier of chess is inspired by a FOL theory approved by a chess expert and the examples are defined as sequences of moves within a game. Starting from a standard revision system, we argue that abduction and negation are also required to best address this problem. Experimental results show the effectiveness of our approach.

Integrated Approach of Agri-nanotechnology: Challenges and Future Trends

PubMed Central

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

2017-01-01

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

iSAW: Integrating Structure, Actors, and Water to study socio-hydro-ecological systems

NASA Astrophysics Data System (ADS)

Hale, Rebecca L.; Armstrong, Andrea; Baker, Michelle A.; Bedingfield, Sean; Betts, David; Buahin, Caleb; Buchert, Martin; Crowl, Todd; Dupont, R. Ryan; Ehleringer, James R.; Endter-Wada, Joanna; Flint, Courtney; Grant, Jacqualine; Hinners, Sarah; Horsburgh, Jeffery S.; Jackson-Smith, Douglas; Jones, Amber S.; Licon, Carlos; Null, Sarah E.; Odame, Augustina; Pataki, Diane E.; Rosenberg, David; Runburg, Madlyn; Stoker, Philip; Strong, Courtenay

2015-03-01

Urbanization, climate, and ecosystem change represent major challenges for managing water resources. Although water systems are complex, a need exists for a generalized representation of these systems to identify important components and linkages to guide scientific inquiry and aid water management. We developed an integrated Structure-Actor-Water framework (iSAW) to facilitate the understanding of and transitions to sustainable water systems. Our goal was to produce an interdisciplinary framework for water resources research that could address management challenges across scales (e.g., plot to region) and domains (e.g., water supply and quality, transitioning, and urban landscapes). The framework was designed to be generalizable across all human-environment systems, yet with sufficient detail and flexibility to be customized to specific cases. iSAW includes three major components: structure (natural, built, and social), actors (individual and organizational), and water (quality and quantity). Key linkages among these components include: (1) ecological/hydrologic processes, (2) ecosystem/geomorphic feedbacks, (3) planning, design, and policy, (4) perceptions, information, and experience, (5) resource access and risk, and (6) operational water use and management. We illustrate the flexibility and utility of the iSAW framework by applying it to two research and management problems: understanding urban water supply and demand in a changing climate and expanding use of green storm water infrastructure in a semi-arid environment. The applications demonstrate that a generalized conceptual model can identify important components and linkages in complex and diverse water systems and facilitate communication about those systems among researchers from diverse disciplines.

The Challenges of Reintegrating Indigenous Youth after Their Release from Detention

ERIC Educational Resources Information Center

Dawes, Glenn Desmond

2011-01-01

One of the greatest challenges for the juvenile justice system is to successfully reintegrate young offenders back to their communities so that they do not re-offend and return to detention. This challenge is even greater for young Aboriginal and Torres Strait Islander youth who are over-represented in the Queensland juvenile justice system in…

Knowledge Is Power: The Issue of Censorship in Middle Grades Literacy Instruction

ERIC Educational Resources Information Center

Whitney, Jennifer D.

2007-01-01

Book challenges have become more and more frequent in recent years. In particular, those books that address issues most relevant to preteens and teenagers seem to be the object of many challenges. Many of the hundreds of challenged works represent literary classics and high-quality writing for young audiences. Teachers, administrators and other…

The Challenge of Separating Effects of Simultaneous Education Projects on Student Achievement

ERIC Educational Resources Information Center

Ma, Xin; Ma, Lingling

2009-01-01

When multiple education projects operate in an overlapping or rear-ended manner, it is always a challenge to separate unique project effects on schooling outcomes. Our analysis represents a first attempt to address this challenge. A three-level hierarchical linear model (HLM) was presented as a general analytical framework to separate program…

Sawja: Static Analysis Workshop for Java

NASA Astrophysics Data System (ADS)

Hubert, Laurent; Barré, Nicolas; Besson, Frédéric; Demange, Delphine; Jensen, Thomas; Monfort, Vincent; Pichardie, David; Turpin, Tiphaine

Static analysis is a powerful technique for automatic verification of programs but raises major engineering challenges when developing a full-fledged analyzer for a realistic language such as Java. Efficiency and precision of such a tool rely partly on low level components which only depend on the syntactic structure of the language and therefore should not be redesigned for each implementation of a new static analysis. This paper describes the Sawja library: a static analysis workshop fully compliant with Java 6 which provides OCaml modules for efficiently manipulating Java bytecode programs. We present the main features of the library, including i) efficient functional data-structures for representing a program with implicit sharing and lazy parsing, ii) an intermediate stack-less representation, and iii) fast computation and manipulation of complete programs. We provide experimental evaluations of the different features with respect to time, memory and precision.

The "Batman flap": a novel technique to repair a large central glabellar defect.

PubMed

Puviani, Mario; Curci, Marco

2018-04-01

Given the critical position of central glabella among the frontal, nasal, and supraorbital aesthetic subunits of the face, the reconstruction of large defects in this area represents a surgical challenge. We describe a surgical technique based on a modified, curved, A-T flap to repair a large glabellar defect. Our modification is useful for large glabellar defects because it enables the distribution of the tension all over the reconstruction sides, avoiding a stressed central area and the subsequent risk of necrosis; functionally, it respects the eyebrows position and since the advancement is parallel to their major axes, it avoids the reduction of the distance between them. The "Batman flap" enables reconstructing a glabellar defect, with a good aesthetical result and the respect of the relevant aesthetical subunits. © 2017 The International Society of Dermatology.

Fostering collaborative research for rare genetic disease: the example of niemann-pick type C disease.

PubMed

Walkley, Steven U; Davidson, Cristin D; Jacoby, Jonathan; Marella, Philip D; Ottinger, Elizabeth A; Austin, Christopher P; Porter, Forbes D; Vite, Charles H; Ory, Daniel S

2016-12-01

Rare disease represents one of the most significant issues facing the medical community and health care providers worldwide, yet the majority of these disorders never emerge from their obscurity, drawing little attention from the medical community or the pharmaceutical industry. The challenge therefore is how best to mobilize rare disease stakeholders to enhance basic, translational and clinical research to advance understanding of pathogenesis and accelerate therapy development. Here we describe a rare, fatal brain disorder known as Niemann-Pick type C (NPC) and an innovative research collaborative known as Support of Accelerated Research for NPC (SOAR-NPC) which illustrates one pathway through which knowledge of a rare disease and its possible treatments are being successfully advanced. Use of the "SOAR" mechanism, we believe, offers a blueprint for similar advancement for many other rare disorders.

Initial strides for invent-VTE: Towards global collaboration to accelerate clinical research in venous thromboembolism.

PubMed

Rodger, Marc; Langlois, Nicole; Middeldorp, Saskia; Kahn, Susan; Sandset, Per Morten; Brighton, Timothy; Huisman, Menno V; Meyer, Guy; Konstantinides, Stavros; Ageno, Walter; Morange, Pierre; Garcia, David; Kreuziger, Lisa Baumann; Young, Laura; Key, Nigel; Monreal, Manuel; Jiménez, David

2018-03-01

Venous thromboembolism (VTE) represents a major global burden of disease and requires collaborative efforts to conduct large, high-quality investigator-initiated and academically sponsored studies addressing the most relevant clinical questions. Owing to increasing regulatory requirements, the highly competitive nature of peer-reviewed funding and costs associated with conducting large, multinational clinical trials, completing practice-changing research constitutes a growing challenge for clinical investigators. As clinical trialists interested in VTE, we founded INVENT (International Network of Venous Thromboembolism Clinical Research Networks) in an effort to promote and accelerate patient-oriented, investigator-initiated, international collaborative research, to identify, prioritize and answer key clinical research questions for patients with VTE. We report on our activities to formalize the INVENT network and our accomplishments in our first year. Copyright © 2018 Elsevier Ltd. All rights reserved.

Direct N-alkylation of unprotected amino acids with alcohols

PubMed Central

Yan, Tao; Feringa, Ben L.; Barta, Katalin

2017-01-01

N-alkyl amino acids find widespread application as highly valuable, renewable building blocks. However, traditional synthesis methodologies to obtain these suffer from serious limitations, providing a major challenge to develop sustainable alternatives. We report the first powerful catalytic strategy for the direct N-alkylation of unprotected α-amino acids with alcohols. This method is highly selective, produces water as the only side product leading to a simple purification procedure, and a variety of α-amino acids are mono- or di-N-alkylated, in most cases with excellent retention of optical purity. The hydrophobicity of the products is tunable, and even simple peptides are selectively alkylated. An iron-catalyzed route to mono-N-alkyl amino acids using renewable fatty alcohols is also described that represents an ideal green transformation for obtaining fully bio-based surfactants. PMID:29226249

Genetic Heterogeneity and Clonal Evolution of Tumor Cells and their Impact on Precision Cancer Medicine.

PubMed

Sabaawy, Hatem E

2013-11-18

The efficacy of targeted therapies in leukemias and solid tumors depends upon the accurate detection and sustained targeting of initial and evolving driver mutations and/or aberrations in cancer cells. Tumor clonal evolution of the diverse populations of cancer cells during cancer progression contributes to the longitudinal variations of clonal, morphological, anatomical, and molecular heterogeneity of tumors. Moreover, drug-resistant subclones present at initiation of therapy or emerging as a result of targeted therapies represent major challenges for achieving success of personalized therapies in providing meaningful improvement in cancer survival rates. Here, I briefly portray tumor cell clonal evolution at the cellular and molecular levels, and present the multiple types of genetic heterogeneity in tumors, with a focus on their impact on the implementation of personalized or precision cancer medicine.

Expansion of chemical space for collaborative lead generation and drug discovery: the European Lead Factory Perspective.

PubMed

Karawajczyk, Anna; Giordanetto, Fabrizio; Benningshof, Jorg; Hamza, Daniel; Kalliokoski, Tuomo; Pouwer, Kees; Morgentin, Remy; Nelson, Adam; Müller, Gerhard; Piechot, Alexander; Tzalis, Dimitrios

2015-11-01

High-throughput screening (HTS) represents a major cornerstone of drug discovery. The availability of an innovative, relevant and high-quality compound collection to be screened often dictates the final fate of a drug discovery campaign. Given that the chemical space to be sampled in research programs is practically infinite and sparsely populated, significant efforts and resources need to be invested in the generation and maintenance of a competitive compound collection. The European Lead Factory (ELF) project is addressing this challenge by leveraging the diverse experience and know-how of academic groups and small and medium enterprises (SMEs) engaged in synthetic and/or medicinal chemistry. Here, we describe the novelty, diversity, structural complexity, physicochemical characteristics and overall attractiveness of this first batch of ELF compounds for HTS purposes. Copyright © 2015 Elsevier Ltd. All rights reserved.

A review of estimation of distribution algorithms in bioinformatics

PubMed Central

Armañanzas, Rubén; Inza, Iñaki; Santana, Roberto; Saeys, Yvan; Flores, Jose Luis; Lozano, Jose Antonio; Peer, Yves Van de; Blanco, Rosa; Robles, Víctor; Bielza, Concha; Larrañaga, Pedro

2008-01-01

Evolutionary search algorithms have become an essential asset in the algorithmic toolbox for solving high-dimensional optimization problems in across a broad range of bioinformatics problems. Genetic algorithms, the most well-known and representative evolutionary search technique, have been the subject of the major part of such applications. Estimation of distribution algorithms (EDAs) offer a novel evolutionary paradigm that constitutes a natural and attractive alternative to genetic algorithms. They make use of a probabilistic model, learnt from the promising solutions, to guide the search process. In this paper, we set out a basic taxonomy of EDA techniques, underlining the nature and complexity of the probabilistic model of each EDA variant. We review a set of innovative works that make use of EDA techniques to solve challenging bioinformatics problems, emphasizing the EDA paradigm's potential for further research in this domain. PMID:18822112

Oral CCR5 inhibitors: will they make it through?

PubMed

Biswas, Priscilla; Nozza, Silvia; Scarlatti, Gabriella; Lazzarin, Adriano; Tambussi, Giuseppe

2006-05-01

The therapeutic armamentarium against HIV has recently gained a drug belonging to a novel class of antiretrovirals, the entry inhibitors. The last decade has driven an in-depth knowledge of the HIV entry process, unravelling the multiple engagements of the HIV envelope proteins with the cellular receptorial complex that is composed of a primary receptor (CD4) and a co-receptor (CCR5 or CXCR4). The vast majority of HIV-infected subjects exhibit biological viral variants that use CCR5 as a co-receptor. Individuals with a mutated CCR5 gene, both homo- and heterozygotes, appear to be healthy. For these and other reasons, CCR5 represents an appealing target for treatment intervention, although certain challenges can not be ignored. Promising small-molecule, orally bioavailable CCR5 antagonists are under development for the treatment of HIV-1 infection.

Diagnosis, prevention, and management of bleeding episodes in Philadelphia-negative myeloproliferative neoplasms: recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO) and the Society of Thrombosis and Hemostasis Research (GTH).

PubMed

Appelmann, Iris; Kreher, Stephan; Parmentier, Stefani; Wolf, Hans-Heinrich; Bisping, Guido; Kirschner, Martin; Bergmann, Frauke; Schilling, Kristina; Brümmendorf, Tim H; Petrides, Petro E; Tiede, Andreas; Matzdorff, Axel; Griesshammer, Martin; Riess, Hanno; Koschmieder, Steffen

2016-04-01

Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPN) comprise a heterogeneous group of chronic hematologic malignancies. The quality of life, morbidity, and mortality of patients with MPN are primarily affected by disease-related symptoms, thromboembolic and hemorrhagic complications, and progression to myelofibrosis and acute leukemia. Major bleeding represents a common and important complication in MPN, and the incidence of such bleeding events will become even more relevant in the future due to the increasing disease prevalence and survival of MPN patients. This review discusses the causes, differential diagnoses, prevention, and management of bleeding episodes in patients with MPN, aiming at defining updated standards of care in these often challenging situations.

Understanding the Effects of Sampling on Healthcare Risk Modeling for the Prediction of Future High-Cost Patients

NASA Astrophysics Data System (ADS)

Moturu, Sai T.; Liu, Huan; Johnson, William G.

Rapidly rising healthcare costs represent one of the major issues plaguing the healthcare system. Data from the Arizona Health Care Cost Containment System, Arizona's Medicaid program provide a unique opportunity to exploit state-of-the-art machine learning and data mining algorithms to analyze data and provide actionable findings that can aid cost containment. Our work addresses specific challenges in this real-life healthcare application with respect to data imbalance in the process of building predictive risk models for forecasting high-cost patients. We survey the literature and propose novel data mining approaches customized for this compelling application with specific focus on non-random sampling. Our empirical study indicates that the proposed approach is highly effective and can benefit further research on cost containment in the healthcare industry.